Trial Outcomes & Findings for A Study in Preterm Neonates With Respiratory Distress Syndrome (RDS) Comparing CUROSURF® Administration Through Less Invasive Surfactant Administration (LISA) and Conventional Administration (NCT NCT02772081)

NCT ID: NCT02772081

Last Updated: 2023-11-07

Results Overview

Extent of exposure to study treatment is summarized by treatment group. Number of participants who received 1, 2, or 3 doses of treatment. All neonates received the first administration of Curosurf® 200 mg/kg. In case of lack of efficacy or clinical deterioration, a second dose of Curosurf® 100 mg/kg was administered using the same technique as the first dose. Neonates could receive a third Curosurf® 100 mg/kg dose if needed, administered using a standard technique. Results are presented as the number of neonates who received 1, 2, or 3 doses of Curosurf®, administered.

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 33 participants
• Primary outcome timeframe: First 72 hours of life.
• Results posted on: 2023-11-07

Participant Flow

Participant milestones

Measure	Curosurf LISA Single dose of poractant alfa 200 mg/kg via brief insertion of a thin catheter (CHF 6440) into the trachea in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. LISA combination product (Curosurf+catheter CHF6440): Curosurf administration through brief insertion of a thin catheter into the trachea	Curosurf Endotracheal Tube Single dose of poractant alfa 200 mg/kg via the conventional intubation with endotracheal tube in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. Curosurf through conventional administration (endotracheal tube): Curosurf through conventional administration (endotracheal tube), followed by rapid extubation
Overall Study STARTED	20	13
Overall Study COMPLETED	18	11
Overall Study NOT COMPLETED	2	2

Reasons for withdrawal

Measure	Curosurf LISA Single dose of poractant alfa 200 mg/kg via brief insertion of a thin catheter (CHF 6440) into the trachea in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. LISA combination product (Curosurf+catheter CHF6440): Curosurf administration through brief insertion of a thin catheter into the trachea	Curosurf Endotracheal Tube Single dose of poractant alfa 200 mg/kg via the conventional intubation with endotracheal tube in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. Curosurf through conventional administration (endotracheal tube): Curosurf through conventional administration (endotracheal tube), followed by rapid extubation
Overall Study Physician Decision	1	1
Overall Study Death	1	1

Baseline Characteristics

Neonate and maternal demographic and baseline characteristics are based on the ITT population

Baseline characteristics by cohort

Measure	Curosurf LISA n=19 Participants Single dose of poractant alfa 200 mg/kg via brief insertion of a thin catheter (CHF 6440) into the trachea in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. LISA combination product (Curosurf+catheter CHF6440): Curosurf administration through brief insertion of a thin catheter into the trachea	Curosurf Endotracheal Tube n=12 Participants Single dose of poractant alfa 200 mg/kg via the conventional intubation with endotracheal tube in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. Curosurf through conventional administration (endotracheal tube): Curosurf through conventional administration (endotracheal tube), followed by rapid extubation	Total n=31 Participants Total of all reporting groups
Age, Continuous	27.65 weeks n=19 Participants	27.92 weeks n=12 Participants	27.76 weeks n=31 Participants
Sex: Female, Male Female	8 Participants n=19 Participants	5 Participants n=12 Participants	13 Participants n=31 Participants
Sex: Female, Male Male	11 Participants n=19 Participants	7 Participants n=12 Participants	18 Participants n=31 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=19 Participants	0 Participants n=12 Participants	0 Participants n=31 Participants
Race (NIH/OMB) Asian	1 Participants n=19 Participants	0 Participants n=12 Participants	1 Participants n=31 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=19 Participants	0 Participants n=12 Participants	0 Participants n=31 Participants
Race (NIH/OMB) Black or African American	4 Participants n=19 Participants	3 Participants n=12 Participants	7 Participants n=31 Participants
Race (NIH/OMB) White	11 Participants n=19 Participants	7 Participants n=12 Participants	18 Participants n=31 Participants
Race (NIH/OMB) More than one race	0 Participants n=19 Participants	0 Participants n=12 Participants	0 Participants n=31 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=19 Participants	2 Participants n=12 Participants	5 Participants n=31 Participants
Race/Ethnicity, Customized Hispanic or Latino	5 participants n=19 Participants • Neonate and maternal demographic and baseline characteristics are based on the ITT population	6 participants n=12 Participants • Neonate and maternal demographic and baseline characteristics are based on the ITT population	11 participants n=31 Participants • Neonate and maternal demographic and baseline characteristics are based on the ITT population
Race/Ethnicity, Customized Not Hispanic or Latino	14 participants n=19 Participants • Neonate and maternal demographic and baseline characteristics are based on the ITT population	6 participants n=12 Participants • Neonate and maternal demographic and baseline characteristics are based on the ITT population	20 participants n=31 Participants • Neonate and maternal demographic and baseline characteristics are based on the ITT population
Region of Enrollment United States	19 participants n=19 Participants	12 participants n=12 Participants	31 participants n=31 Participants
Birth weight	1.009 kg n=19 Participants	0.973 kg n=12 Participants	0.995 kg n=31 Participants
APGAR score at 1 minute post-birth	5.6 scores on a scale n=19 Participants	4.8 scores on a scale n=12 Participants	5.3 scores on a scale n=31 Participants
APGAR score at 5 minutes post-birth	7.5 APGAR score n=19 Participants	7.7 APGAR score n=12 Participants	7.6 APGAR score n=31 Participants
Mother's age	30.0 years n=19 Participants	25.8 years n=12 Participants	28.4 years n=31 Participants
Mother's race American Indian or Alaska Native	1 Participants n=19 Participants	0 Participants n=12 Participants	1 Participants n=31 Participants
Mother's race Asian	1 Participants n=19 Participants	0 Participants n=12 Participants	1 Participants n=31 Participants
Mother's race Black or African American	4 Participants n=19 Participants	3 Participants n=12 Participants	7 Participants n=31 Participants
Mother's race White	11 Participants n=19 Participants	8 Participants n=12 Participants	19 Participants n=31 Participants
Mother's race Unknown or Not Reported	2 Participants n=19 Participants	1 Participants n=12 Participants	3 Participants n=31 Participants
Mother's ethnicity Hispanic or Latino	5 Participants n=19 Participants	6 Participants n=12 Participants	11 Participants n=31 Participants
Mother's ethnicity Not Hispanic or Latino	13 Participants n=19 Participants	5 Participants n=12 Participants	18 Participants n=31 Participants
Mother's ethnicity Data missing	1 Participants n=19 Participants	1 Participants n=12 Participants	2 Participants n=31 Participants
Antibiotics taken - YES	9 Participants n=19 Participants	8 Participants n=12 Participants	17 Participants n=31 Participants
Corticosteroids taken -- YES	14 Participants n=19 Participants	11 Participants n=12 Participants	25 Participants n=31 Participants
Number of days from last corticosteroid dose up to birth, 0-1 days	8 days n=14 Participants • The information refers to the mothers of enrolled subjects, who took antibiotics and corticosteroids during pregnancy.	5 days n=11 Participants • The information refers to the mothers of enrolled subjects, who took antibiotics and corticosteroids during pregnancy.	13 days n=25 Participants • The information refers to the mothers of enrolled subjects, who took antibiotics and corticosteroids during pregnancy.
Number of days from last corticosteroid dose up to birth, 2-7 days	3 days n=14 Participants • The information refers to the mothers of enrolled subjects, who took antibiotics and corticosteroids during pregnancy.	6 days n=11 Participants • The information refers to the mothers of enrolled subjects, who took antibiotics and corticosteroids during pregnancy.	9 days n=25 Participants • The information refers to the mothers of enrolled subjects, who took antibiotics and corticosteroids during pregnancy.
Number of days from last corticosteroid dose up to birth, >7 days	3 days n=14 Participants • The information refers to the mothers of enrolled subjects, who took antibiotics and corticosteroids during pregnancy.	0 days n=11 Participants • The information refers to the mothers of enrolled subjects, who took antibiotics and corticosteroids during pregnancy.	3 days n=25 Participants • The information refers to the mothers of enrolled subjects, who took antibiotics and corticosteroids during pregnancy.
Type of delivery C-section with labor	2 Participants n=19 Participants	3 Participants n=12 Participants	5 Participants n=31 Participants
Type of delivery C-section without labor	10 Participants n=19 Participants	4 Participants n=12 Participants	14 Participants n=31 Participants
Type of delivery Emergency C-section	5 Participants n=19 Participants	3 Participants n=12 Participants	8 Participants n=31 Participants
Type of delivery Spontaneous	2 Participants n=19 Participants	2 Participants n=12 Participants	4 Participants n=31 Participants

PRIMARY outcome

Timeframe: First 72 hours of life.

Population: Safety population (SAF): All randomized neonates who received at least one dose of study treatment.

Extent of exposure to study treatment is summarized by treatment group. Number of participants who received 1, 2, or 3 doses of treatment.

All neonates received the first administration of Curosurf® 200 mg/kg. In case of lack of efficacy or clinical deterioration, a second dose of Curosurf® 100 mg/kg was administered using the same technique as the first dose. Neonates could receive a third Curosurf® 100 mg/kg dose if needed, administered using a standard technique. Results are presented as the number of neonates who received 1, 2, or 3 doses of Curosurf®, administered.

Outcome measures

Measure	Curosurf LISA n=19 Participants Single dose of poractant alfa 200 mg/kg via brief insertion of a thin catheter (CHF 6440) into the trachea in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. LISA combination product (Curosurf+catheter CHF6440): Curosurf administration through brief insertion of a thin catheter into the trachea	Curosurf Endotracheal Tube n=12 Participants Single dose of poractant alfa 200 mg/kg via the conventional intubation with endotracheal tube in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. Curosurf through conventional administration (endotracheal tube): Curosurf through conventional administration (endotracheal tube), followed by rapid extubation
Safety: Study Treatment Administration: Number of Participants Who Received 1, 2, or 3 Doses of Treatment Number of Curosurf® dose, n=1 dose	13 Participants	9 Participants
Safety: Study Treatment Administration: Number of Participants Who Received 1, 2, or 3 Doses of Treatment Number of Curosurf® doses, n=2 doses	4 Participants	2 Participants
Safety: Study Treatment Administration: Number of Participants Who Received 1, 2, or 3 Doses of Treatment Number of Curosurf® doses, n=3 doses	2 Participants	1 Participants

PRIMARY outcome

Timeframe: At first surfactant administration, up to Day 1.

Population: Safety population (SAF): All randomized neonates who received at least one dose of study treatment.

Number of participants for whom the first attempt failed to insert the catheter/endotracheal tube and the percentage of neonates with first failed attempt, is presented by treatment group.

Outcome measures

Measure	Curosurf LISA n=19 Participants Single dose of poractant alfa 200 mg/kg via brief insertion of a thin catheter (CHF 6440) into the trachea in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. LISA combination product (Curosurf+catheter CHF6440): Curosurf administration through brief insertion of a thin catheter into the trachea	Curosurf Endotracheal Tube n=12 Participants Single dose of poractant alfa 200 mg/kg via the conventional intubation with endotracheal tube in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. Curosurf through conventional administration (endotracheal tube): Curosurf through conventional administration (endotracheal tube), followed by rapid extubation
Safety: Study Treatment Administration: Number of Participants for Whom the First Attempt Failed to Insert the Catheter/Endotracheal Tube	5 Participants	5 Participants

PRIMARY outcome

Timeframe: At first surfactant administration, up to Day 1 or at second administration, up to 2 days.

Population: Safety population (SAF): All randomized neonates who received at least one dose of study treatment.

Number of manoeuvres (attempts) discontinued, due to neonate's severe destabilization is presented by treatment group.

Outcome measures

Measure	Curosurf LISA n=19 Participants Single dose of poractant alfa 200 mg/kg via brief insertion of a thin catheter (CHF 6440) into the trachea in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. LISA combination product (Curosurf+catheter CHF6440): Curosurf administration through brief insertion of a thin catheter into the trachea	Curosurf Endotracheal Tube n=12 Participants Single dose of poractant alfa 200 mg/kg via the conventional intubation with endotracheal tube in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. Curosurf through conventional administration (endotracheal tube): Curosurf through conventional administration (endotracheal tube), followed by rapid extubation
Safety: Study Treatment Administration: Number of Maneuvers Discontinued Due to Neonate's Severe Destabilization First administration	0.1 Number of maneuvers (attempts) Interval 0.0 to 1.0	0.0 Number of maneuvers (attempts) Interval 0.0 to 0.0
Safety: Study Treatment Administration: Number of Maneuvers Discontinued Due to Neonate's Severe Destabilization Second administration	0.3 Number of maneuvers (attempts) Interval 0.0 to 1.0	0.0 Number of maneuvers (attempts) Interval 0.0 to 0.0

PRIMARY outcome

Timeframe: At first surfactant administration, up to Day 1 or at second administration, up to 2 days.

Population: Safety population (SAF): All randomized neonates who received at least one dose of study treatment.

Number of attempts required to achieve first successful insertion is presented by treatment group.

Outcome measures

Measure	Curosurf LISA n=19 Participants Single dose of poractant alfa 200 mg/kg via brief insertion of a thin catheter (CHF 6440) into the trachea in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. LISA combination product (Curosurf+catheter CHF6440): Curosurf administration through brief insertion of a thin catheter into the trachea	Curosurf Endotracheal Tube n=12 Participants Single dose of poractant alfa 200 mg/kg via the conventional intubation with endotracheal tube in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. Curosurf through conventional administration (endotracheal tube): Curosurf through conventional administration (endotracheal tube), followed by rapid extubation
Safety: Study Treatment Administration: Number of Attempts to First Successful Insertion First administration	1.3 Number of maneuvers (attempts) Interval 1.0 to 2.0	1.8 Number of maneuvers (attempts) Interval 1.0 to 5.0
Safety: Study Treatment Administration: Number of Attempts to First Successful Insertion Second administration	2.0 Number of maneuvers (attempts) Interval 1.0 to 3.0	1.0 Number of maneuvers (attempts) Interval 1.0 to 1.0

PRIMARY outcome

Timeframe: At first surfactant administration, up to Day 1 or at second administration, up to 2 days.

Population: Safety population (SAF): All randomized neonates who received at least one dose of study treatment.

Number of device misallocation for LISA administration group (esophageal insertion).

Data was not collected from participants in the "Curosurf Endotracheal Tube" -- the control arm of the study, because it is not applicable.

Outcome measures

Measure	Curosurf LISA n=19 Participants Single dose of poractant alfa 200 mg/kg via brief insertion of a thin catheter (CHF 6440) into the trachea in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. LISA combination product (Curosurf+catheter CHF6440): Curosurf administration through brief insertion of a thin catheter into the trachea	Curosurf Endotracheal Tube Single dose of poractant alfa 200 mg/kg via the conventional intubation with endotracheal tube in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. Curosurf through conventional administration (endotracheal tube): Curosurf through conventional administration (endotracheal tube), followed by rapid extubation
Safety: Study Treatment Administration: Number of Device Misallocation for LISA Administration Group (Esophageal Insertion) First administration	0.2 Number of maneuvers (attempts) Interval 0.0 to 1.0	—
Safety: Study Treatment Administration: Number of Device Misallocation for LISA Administration Group (Esophageal Insertion) Second administration	0.0 Number of maneuvers (attempts) Interval 0.0 to 0.0	—

PRIMARY outcome

Timeframe: At first surfactant administration, up to Day 1 or at second administration, up to 2 days.

Population: Safety population (SAF): All randomized neonates who received at least one dose of study treatment.

Duration of surfactant administration is presented by treatment group.

Outcome measures

Measure	Curosurf LISA n=19 Participants Single dose of poractant alfa 200 mg/kg via brief insertion of a thin catheter (CHF 6440) into the trachea in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. LISA combination product (Curosurf+catheter CHF6440): Curosurf administration through brief insertion of a thin catheter into the trachea	Curosurf Endotracheal Tube n=12 Participants Single dose of poractant alfa 200 mg/kg via the conventional intubation with endotracheal tube in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. Curosurf through conventional administration (endotracheal tube): Curosurf through conventional administration (endotracheal tube), followed by rapid extubation
Safety: Study Treatment Administration: Duration of Surfactant Administration First administration	1.8 minutes Interval 1.0 to 5.0	2.3 minutes Interval 1.0 to 4.0
Safety: Study Treatment Administration: Duration of Surfactant Administration Second administration	2.3 minutes Interval 1.0 to 4.0	1.7 minutes Interval 0.0 to 3.0

PRIMARY outcome

Timeframe: At first surfactant administration, up to Day 1 or at second administration, up to 2 days.

Population: Safety population (SAF): All randomized neonates who received at least one dose of study treatment.

Duration of the whole procedure (starting from the insertion of laryngoscope up to the removal of the catheter/ETT), is presented by treatment group.

Outcome measures

Measure	Curosurf LISA n=19 Participants Single dose of poractant alfa 200 mg/kg via brief insertion of a thin catheter (CHF 6440) into the trachea in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. LISA combination product (Curosurf+catheter CHF6440): Curosurf administration through brief insertion of a thin catheter into the trachea	Curosurf Endotracheal Tube n=12 Participants Single dose of poractant alfa 200 mg/kg via the conventional intubation with endotracheal tube in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. Curosurf through conventional administration (endotracheal tube): Curosurf through conventional administration (endotracheal tube), followed by rapid extubation
Safety: Study Treatment Administration: Duration of the Whole Procedure First administration	3.9 minutes Interval 1.0 to 10.0	7.8 minutes Interval 2.0 to 15.0
Safety: Study Treatment Administration: Duration of the Whole Procedure Second administration	5.8 minutes Interval 2.0 to 10.0	3.0 minutes Interval 3.0 to 3.0

SECONDARY outcome

Timeframe: First 72 hours of life, Up to 28 days Post-Natal Age (PNA), Up to 36 weeks Post-Menstrual Age (PMA).

Population: Intention-to-treat population (ITT): All randomized neonates who received at least one dose of study treatment.

The duration of oxygen alone supplementation and any non-invasive ventilation (NIV) during the study are presented by treatment group.

PMA=Post-Menstrual Age PNA=Post-Natal Age

Outcome measures

Measure	Curosurf LISA n=19 Participants Single dose of poractant alfa 200 mg/kg via brief insertion of a thin catheter (CHF 6440) into the trachea in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. LISA combination product (Curosurf+catheter CHF6440): Curosurf administration through brief insertion of a thin catheter into the trachea	Curosurf Endotracheal Tube n=12 Participants Single dose of poractant alfa 200 mg/kg via the conventional intubation with endotracheal tube in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. Curosurf through conventional administration (endotracheal tube): Curosurf through conventional administration (endotracheal tube), followed by rapid extubation
Efficacy: Duration of Oxygen Alone Supplementation and Any Non-Invasive Ventilation (NIV) Duration of standalone oxygen supplementation	16.4 days Interval 3.0 to 27.0	16.4 days Interval 3.0 to 52.0
Efficacy: Duration of Oxygen Alone Supplementation and Any Non-Invasive Ventilation (NIV) Duration of NIV	45.7 days Interval 2.0 to 87.0	38.3 days Interval 1.0 to 70.0

SECONDARY outcome

Timeframe: First 72 hours of life.

Population: Intention-to-treat population (ITT): All randomized neonates who received at least one dose of study treatment.

A summary of the percentage of neonates requiring at least one additional dose of surfactant, and respective statistical analysis, is presented by treatment group i.e. 2 or 3 doses of surfactant .

Outcome measures

Measure	Curosurf LISA n=6 Participants Single dose of poractant alfa 200 mg/kg via brief insertion of a thin catheter (CHF 6440) into the trachea in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. LISA combination product (Curosurf+catheter CHF6440): Curosurf administration through brief insertion of a thin catheter into the trachea	Curosurf Endotracheal Tube n=3 Participants Single dose of poractant alfa 200 mg/kg via the conventional intubation with endotracheal tube in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. Curosurf through conventional administration (endotracheal tube): Curosurf through conventional administration (endotracheal tube), followed by rapid extubation
Efficacy: Neonates Needing Additional 2 or 3 Doses of Surfactant Additional dose of surfactant (n=2 doses)	4 Participants	2 Participants
Efficacy: Neonates Needing Additional 2 or 3 Doses of Surfactant Additional dose of surfactant (n=3 doses)	2 Participants	1 Participants

SECONDARY outcome

Timeframe: First 72 hours of life.

Population: Intention-to-treat population (ITT): All randomized neonates who received at least one dose of study treatment.

A summary of the percentage of neonates requiring at least one additional dose of surfactant, and respective statistical analysis, is presented by treatment group.

Outcome measures

Measure	Curosurf LISA n=19 Participants Single dose of poractant alfa 200 mg/kg via brief insertion of a thin catheter (CHF 6440) into the trachea in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. LISA combination product (Curosurf+catheter CHF6440): Curosurf administration through brief insertion of a thin catheter into the trachea	Curosurf Endotracheal Tube n=12 Participants Single dose of poractant alfa 200 mg/kg via the conventional intubation with endotracheal tube in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. Curosurf through conventional administration (endotracheal tube): Curosurf through conventional administration (endotracheal tube), followed by rapid extubation
Efficacy: Neonates Needing Additional Surfactant Doses	6 Participants	3 Participants

SECONDARY outcome

Timeframe: Pre-procedure, at time 0 (T0, end of surfactant instillation) and post treatment after T0 at 5, 15, 30 minutes, at 1, 6, 12, 24, 48, 72, and 120 hours, on Day 28 PNA, 36 weeks PMA.

Population: Intention-to-treat population (ITT): All randomized neonates who received at least one dose of study treatment.

The mean SpO2/FiO2 ratio values at timepoints up to and including 120 hours post-treatment, and respective statistical analyses, are summarized by treatment group.

Outcome measures

Measure	Curosurf LISA n=19 Participants Single dose of poractant alfa 200 mg/kg via brief insertion of a thin catheter (CHF 6440) into the trachea in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. LISA combination product (Curosurf+catheter CHF6440): Curosurf administration through brief insertion of a thin catheter into the trachea	Curosurf Endotracheal Tube n=12 Participants Single dose of poractant alfa 200 mg/kg via the conventional intubation with endotracheal tube in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. Curosurf through conventional administration (endotracheal tube): Curosurf through conventional administration (endotracheal tube), followed by rapid extubation
Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio Pre-procedure	2.368 ratio Standard Deviation 0.794	2.052 ratio Standard Deviation 0.659
Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio T0	1.796 ratio Standard Deviation 1.035	2.463 ratio Standard Deviation 1.221
Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio 5 mins	3.113 ratio Standard Deviation 1.164	2.657 ratio Standard Deviation 1.376
Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio 15 mins	3.438 ratio Standard Deviation 1.116	3.010 ratio Standard Deviation 1.229
Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio 30 mins	3.960 ratio Standard Deviation 0.875	3.253 ratio Standard Deviation 1.358
Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio 1 hour	4.106 ratio Standard Deviation 0.869	3.577 ratio Standard Deviation 0.921
Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio 6 hours	4.152 ratio Standard Deviation 0.776	3.919 ratio Standard Deviation 1.061
Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio 12 hours	4.090 ratio Standard Deviation 0.811	3.976 ratio Standard Deviation 1.172
Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio 24 hours	4.139 ratio Standard Deviation 0.730	3.829 ratio Standard Deviation 0.945
Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio 48 hours	4.046 ratio Standard Deviation 0.568	3.653 ratio Standard Deviation 0.952
Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio 72 hours	3.988 ratio Standard Deviation 0.887	3.916 ratio Standard Deviation 0.944
Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio 120 hours	4.205 ratio Standard Deviation 0.698	4.263 ratio Standard Deviation 0.862
Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio Day 28 PNA	3.975 ratio Standard Deviation 1.104	3.804 ratio Standard Deviation 0.936
Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio 36 weeks PMA	3.571 ratio Standard Deviation 0.535	3.840 ratio Standard Deviation 0.599

SECONDARY outcome

Timeframe: Pre-procedure, at time 0 (T0, end of surfactant instillation) and post treatment after T0 at 5, 15, 30 minutes, at 1, 6, 12, 24, 48, 72, and 120 hours, on Day 28 PNA, 36 weeks PMA.

Population: Intention-to-treat population (ITT): All randomized neonates who received at least one dose of study treatment.

The FiO2 values at timepoints up to and including 120 hours post-treatment and the changes from pre-procedure to each of those timepoints are presented by treatment group.

The fraction of inspired oxygen (FiO2) is the concentration of oxygen in the gas mixture.

Outcome measures

Measure	Curosurf LISA n=19 Participants Single dose of poractant alfa 200 mg/kg via brief insertion of a thin catheter (CHF 6440) into the trachea in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. LISA combination product (Curosurf+catheter CHF6440): Curosurf administration through brief insertion of a thin catheter into the trachea	Curosurf Endotracheal Tube n=12 Participants Single dose of poractant alfa 200 mg/kg via the conventional intubation with endotracheal tube in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. Curosurf through conventional administration (endotracheal tube): Curosurf through conventional administration (endotracheal tube), followed by rapid extubation
Efficacy: Fraction of Inspired Oxygen (FiO2) 6 hours	0.244 fraction of inspired oxygen Standard Deviation 0.077	0.274 fraction of inspired oxygen Standard Deviation 0.131
Efficacy: Fraction of Inspired Oxygen (FiO2) Pre-procedure	0.435 fraction of inspired oxygen Standard Deviation 0.151	0.524 fraction of inspired oxygen Standard Deviation 0.235
Efficacy: Fraction of Inspired Oxygen (FiO2) T0	0.569 fraction of inspired oxygen Standard Deviation 0.252	0.475 fraction of inspired oxygen Standard Deviation 0.250
Efficacy: Fraction of Inspired Oxygen (FiO2) 5 mins	0.365 fraction of inspired oxygen Standard Deviation 0.197	0.457 fraction of inspired oxygen Standard Deviation 0.260
Efficacy: Fraction of Inspired Oxygen (FiO2) 15 mins	0.321 fraction of inspired oxygen Standard Deviation 0.199	0.373 fraction of inspired oxygen Standard Deviation 0.186
Efficacy: Fraction of Inspired Oxygen (FiO2) 30 mins	0.257 fraction of inspired oxygen Standard Deviation 0.090	0.372 fraction of inspired oxygen Standard Deviation 0.258
Efficacy: Fraction of Inspired Oxygen (FiO2) 1 hour	0.251 fraction of inspired oxygen Standard Deviation 0.108	0.279 fraction of inspired oxygen Standard Deviation 0.084
Efficacy: Fraction of Inspired Oxygen (FiO2) 12 hours	0.246 fraction of inspired oxygen Standard Deviation 0.075	0.290 fraction of inspired oxygen Standard Deviation 0.225
Efficacy: Fraction of Inspired Oxygen (FiO2) 24 hours	0.238 fraction of inspired oxygen Standard Deviation 0.064	0.269 fraction of inspired oxygen Standard Deviation 0.113
Efficacy: Fraction of Inspired Oxygen (FiO2) 48 hours	0.239 fraction of inspired oxygen Standard Deviation 0.033	0.285 fraction of inspired oxygen Standard Deviation 0.133
Efficacy: Fraction of Inspired Oxygen (FiO2) 72 hours	0.257 fraction of inspired oxygen Standard Deviation 0.088	0.262 fraction of inspired oxygen Standard Deviation 0.099
Efficacy: Fraction of Inspired Oxygen (FiO2) 120 hours	0.237 fraction of inspired oxygen Standard Deviation 0.049	0.243 fraction of inspired oxygen Standard Deviation 0.099
Efficacy: Fraction of Inspired Oxygen (FiO2) Day 28 PNA	0.285 fraction of inspired oxygen Standard Deviation 0.188	0.272 fraction of inspired oxygen Standard Deviation 0.091
Efficacy: Fraction of Inspired Oxygen (FiO2) 36 weeks PMA	0.270 fraction of inspired oxygen Standard Deviation 0.029	0.254 fraction of inspired oxygen Standard Deviation 0.033

SECONDARY outcome

Timeframe: Pre-procedure, at time 0 (T0, end of surfactant instillation) and post treatment after T0 at 5, 15, 30 minutes, at 1, 6, 12, 24, 48, 72, and 120 hours, on Day 28 PNA, 36 weeks PMA.

Population: Intention-to-treat population (ITT): All randomized neonates who received at least one dose of study treatment.

The mean SpO2 values at timepoints up to and including 120 hours post-treatment are summarized by treatment group.

Oxygen saturation (SpO2) is a measurement of how much oxygen the blood is carrying as a percentage of the maximum it could carry.

Outcome measures

Measure	Curosurf LISA n=19 Participants Single dose of poractant alfa 200 mg/kg via brief insertion of a thin catheter (CHF 6440) into the trachea in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. LISA combination product (Curosurf+catheter CHF6440): Curosurf administration through brief insertion of a thin catheter into the trachea	Curosurf Endotracheal Tube n=12 Participants Single dose of poractant alfa 200 mg/kg via the conventional intubation with endotracheal tube in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. Curosurf through conventional administration (endotracheal tube): Curosurf through conventional administration (endotracheal tube), followed by rapid extubation
Efficacy: Preductal Oxygen Saturation (SpO2) Pre-procedure	92.7 percentage of oxygen saturation Standard Deviation 3.0	94.3 percentage of oxygen saturation Standard Deviation 3.4
Efficacy: Preductal Oxygen Saturation (SpO2) T0	81.1 percentage of oxygen saturation Standard Deviation 17.9	93.3 percentage of oxygen saturation Standard Deviation 6.6
Efficacy: Preductal Oxygen Saturation (SpO2) 6 hours	96.1 percentage of oxygen saturation Standard Deviation 2.6	94.8 percentage of oxygen saturation Standard Deviation 2.7
Efficacy: Preductal Oxygen Saturation (SpO2) Day 28 PNA	96.3 percentage of oxygen saturation Standard Deviation 3.4	96.0 percentage of oxygen saturation Standard Deviation 2.9
Efficacy: Preductal Oxygen Saturation (SpO2) 72 hours	95.5 percentage of oxygen saturation Standard Deviation 2.9	93.8 percentage of oxygen saturation Standard Deviation 3.6
Efficacy: Preductal Oxygen Saturation (SpO2) 36 weeks PMA	97.0 percentage of oxygen saturation Standard Deviation 3.3	96.6 percentage of oxygen saturation Standard Deviation 2.1
Efficacy: Preductal Oxygen Saturation (SpO2) 5 mins	94.6 percentage of oxygen saturation Standard Deviation 7.6	93.7 percentage of oxygen saturation Standard Deviation 7.1
Efficacy: Preductal Oxygen Saturation (SpO2) 15 mins	92.8 percentage of oxygen saturation Standard Deviation 9.6	93.5 percentage of oxygen saturation Standard Deviation 4.7
Efficacy: Preductal Oxygen Saturation (SpO2) 30 mins	95.0 percentage of oxygen saturation Standard Deviation 4.1	91.3 percentage of oxygen saturation Standard Deviation 10.6
Efficacy: Preductal Oxygen Saturation (SpO2) 1 hour	94.5 percentage of oxygen saturation Standard Deviation 4.8	93.0 percentage of oxygen saturation Standard Deviation 3.7
Efficacy: Preductal Oxygen Saturation (SpO2) 12 hours	94.9 percentage of oxygen saturation Standard Deviation 3.1	91.9 percentage of oxygen saturation Standard Deviation 14.0
Efficacy: Preductal Oxygen Saturation (SpO2) 24 hours	94.5 percentage of oxygen saturation Standard Deviation 3.6	93.9 percentage of oxygen saturation Standard Deviation 4.5
Efficacy: Preductal Oxygen Saturation (SpO2) 48 hours	95.2 percentage of oxygen saturation Standard Deviation 2.9	93.6 percentage of oxygen saturation Standard Deviation 2.9
Efficacy: Preductal Oxygen Saturation (SpO2) 120 hours	96.4 percentage of oxygen saturation Standard Deviation 2.7	95.6 percentage of oxygen saturation Standard Deviation 2.2

SECONDARY outcome

Timeframe: First 72 hours of life, up to 28 days post-natal age (PNA), Up to 36 weeks Post-menstrual age (PMA)

Population: Intention-to-treat population (ITT): All randomized neonates who received at least one dose of study treatment.

The percentage of neonates needing any intubation procedure, outside the initial surfactant administration period (i.e., excluding endotracheal intubation[s] that were required for surfactant administration in the Conventional administration arm), in the first 72 hours of life, in the first 28 days post-natal age (PNA), and within 36 weeks Post-menstrual age (PMA), and respective statistical analyses, are presented.

Outcome measures

Measure	Curosurf LISA n=19 Participants Single dose of poractant alfa 200 mg/kg via brief insertion of a thin catheter (CHF 6440) into the trachea in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. LISA combination product (Curosurf+catheter CHF6440): Curosurf administration through brief insertion of a thin catheter into the trachea	Curosurf Endotracheal Tube n=12 Participants Single dose of poractant alfa 200 mg/kg via the conventional intubation with endotracheal tube in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. Curosurf through conventional administration (endotracheal tube): Curosurf through conventional administration (endotracheal tube), followed by rapid extubation
Efficacy: Percentage of Neonates Needing Any Intubation Procedure, Outside the Initial Surfactant Administration Period Any intubation procedure in first 72 hours of life.	10.5 percentage of participants	25.0 percentage of participants
Efficacy: Percentage of Neonates Needing Any Intubation Procedure, Outside the Initial Surfactant Administration Period Any intubation procedure in first 28 days PNA	31.6 percentage of participants	25.0 percentage of participants
Efficacy: Percentage of Neonates Needing Any Intubation Procedure, Outside the Initial Surfactant Administration Period Any intubation procedure within 36 weeks PMA	31.6 percentage of participants	25.0 percentage of participants

SECONDARY outcome

Timeframe: Up to 28 days PNA, Up to 36 weeks PMA

Population: Intention-to-treat population (ITT): All randomized neonates who received at least one dose of study treatment.

The duration of invasive ventilation (MV) in the first 28 days PNA, and within 36 weeks PMA, are presented by treatment group.

Participants who actually received invasive ventilation are reported in the table below.

Outcome measures

Measure	Curosurf LISA n=19 Participants Single dose of poractant alfa 200 mg/kg via brief insertion of a thin catheter (CHF 6440) into the trachea in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. LISA combination product (Curosurf+catheter CHF6440): Curosurf administration through brief insertion of a thin catheter into the trachea	Curosurf Endotracheal Tube n=12 Participants Single dose of poractant alfa 200 mg/kg via the conventional intubation with endotracheal tube in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. Curosurf through conventional administration (endotracheal tube): Curosurf through conventional administration (endotracheal tube), followed by rapid extubation
Efficacy: Median Duration of Invasive Mechanical Ventilation During the Study Duration of invasive MV in first 28 days PNA	6.0 days Interval 4.0 to 18.0	20.5 days Interval 2.0 to 27.0
Efficacy: Median Duration of Invasive Mechanical Ventilation During the Study Duration of invasive MV within 36 weeks PMA	6 days Interval 4.0 to 18.0	24 days Interval 2.0 to 45.0

SECONDARY outcome

Timeframe: First 72 hours of life

Population: Intention-to-treat population (ITT): All randomized neonates who received at least one dose of study treatment.

The duration of invasive ventilation (MV) in the first 72 hours of life and respective statistical analyses, are presented by treatment group.

Outcome measures

Measure	Curosurf LISA n=3 Participants Single dose of poractant alfa 200 mg/kg via brief insertion of a thin catheter (CHF 6440) into the trachea in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. LISA combination product (Curosurf+catheter CHF6440): Curosurf administration through brief insertion of a thin catheter into the trachea	Curosurf Endotracheal Tube n=4 Participants Single dose of poractant alfa 200 mg/kg via the conventional intubation with endotracheal tube in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. Curosurf through conventional administration (endotracheal tube): Curosurf through conventional administration (endotracheal tube), followed by rapid extubation
Efficacy: Duration of Invasive Mechanical Ventilation During the Study	29.8 hours Interval 6.0 to 67.0	61.4 hours Interval 19.0 to 68.0

SECONDARY outcome

Timeframe: First 72 hours of life, Up to 28 days Post-Natal Age (PNA), Up to 36 weeks PMA

Population: Intention-to-treat population (ITT): All randomized neonates who received at least one dose of study treatment.

The percentage of neonates needing invasive mechanical ventilation (MV) in the first 72 hours of life, in the first 28 days post-natal age (PNA), and within 36 weeks Post-Menstrual Age (PMA), and respective statistical analyses, are presented by treatment group.

Outcome measures

Measure	Curosurf LISA n=19 Participants Single dose of poractant alfa 200 mg/kg via brief insertion of a thin catheter (CHF 6440) into the trachea in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. LISA combination product (Curosurf+catheter CHF6440): Curosurf administration through brief insertion of a thin catheter into the trachea	Curosurf Endotracheal Tube n=12 Participants Single dose of poractant alfa 200 mg/kg via the conventional intubation with endotracheal tube in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. Curosurf through conventional administration (endotracheal tube): Curosurf through conventional administration (endotracheal tube), followed by rapid extubation
Efficacy: Percentage of Neonates Needing Invasive Mechanical Ventilation (MV) During the Study Invasive MV in first 28 days PNA.	6 Participants	4 Participants
Efficacy: Percentage of Neonates Needing Invasive Mechanical Ventilation (MV) During the Study Invasive MV in first 72 hours of life.	3 Participants	4 Participants
Efficacy: Percentage of Neonates Needing Invasive Mechanical Ventilation (MV) During the Study Invasive MV within 36 weeks PMA.	6 Participants	4 Participants

SECONDARY outcome

Timeframe: First 72 hours of life (1h, 6h, 24h, 48h, 72h)

Population: Intention-to-treat population (ITT): All randomized neonates who received at least one dose of study treatment.

The blood gas analysis for blood pH at all timepoints and the changes from pre-procedure to each timepoint are presented.

Results for pH values are based on a scale of 0 to 14. A pH value of 7 is neutral, pH less than 7 is acidic, and pH greater than 7 is basic.

Outcome measures

Measure	Curosurf LISA n=19 Participants Single dose of poractant alfa 200 mg/kg via brief insertion of a thin catheter (CHF 6440) into the trachea in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. LISA combination product (Curosurf+catheter CHF6440): Curosurf administration through brief insertion of a thin catheter into the trachea	Curosurf Endotracheal Tube n=12 Participants Single dose of poractant alfa 200 mg/kg via the conventional intubation with endotracheal tube in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. Curosurf through conventional administration (endotracheal tube): Curosurf through conventional administration (endotracheal tube), followed by rapid extubation
Efficacy: Blood Gas Analysis Parameters -- pH Pre-procedure (actual value)	7.289 units on a pH scale Interval 7.21 to 7.37	7.240 units on a pH scale Interval 7.05 to 7.34
Efficacy: Blood Gas Analysis Parameters -- pH 1 h - post procedure (Change from pre-procedure to 1 hour post-procedure)	0.016 units on a pH scale Interval -0.07 to 0.07	0.038 units on a pH scale Interval -0.04 to 0.15
Efficacy: Blood Gas Analysis Parameters -- pH 6 h - post procedure (Change from pre-procedure to 6 hour post-procedure)	0.044 units on a pH scale Interval -0.04 to 0.13	0.047 units on a pH scale Interval -0.05 to 0.19
Efficacy: Blood Gas Analysis Parameters -- pH 24 h - post procedure (Change from pre-procedure to 24 hour post-procedure)	0.038 units on a pH scale Interval -0.05 to 0.22	0.082 units on a pH scale Interval -0.06 to 0.25
Efficacy: Blood Gas Analysis Parameters -- pH 48 h - post procedure (Change from pre-procedure to 48 hour post-procedure)	0.008 units on a pH scale Interval -0.11 to 0.12	0.072 units on a pH scale Interval -0.08 to 0.19
Efficacy: Blood Gas Analysis Parameters -- pH 72 h - post procedure (Change from pre-procedure to 72 hour post-procedure)	0.001 units on a pH scale Interval -0.16 to 0.14	0.068 units on a pH scale Interval -0.04 to 0.14

SECONDARY outcome

Timeframe: First 72 hours of life (1h, 6h, 24h, 48h, 72h)

Population: Intention-to-treat population (ITT): All randomized neonates who received at least one dose of study treatment.

The blood gas analysis partial pressure of carbon dioxide (pCO2) at all timepoints and the changes from pre-procedure to each timepoint are presented.

Outcome measures

Measure	Curosurf LISA n=19 Participants Single dose of poractant alfa 200 mg/kg via brief insertion of a thin catheter (CHF 6440) into the trachea in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. LISA combination product (Curosurf+catheter CHF6440): Curosurf administration through brief insertion of a thin catheter into the trachea	Curosurf Endotracheal Tube n=12 Participants Single dose of poractant alfa 200 mg/kg via the conventional intubation with endotracheal tube in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. Curosurf through conventional administration (endotracheal tube): Curosurf through conventional administration (endotracheal tube), followed by rapid extubation
Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Carbon Dioxide (pCO2) 1 h - post procedure (Change from pre-procedure to 1 hour post-procedure)	-4.00 mmHg Interval -16.0 to 6.0	-0.85 mmHg Interval -18.0 to 8.0
Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Carbon Dioxide (pCO2) 6 h - post procedure (Change from pre-procedure to 6 hour post-procedure)	-7.55 mmHg Interval -27.0 to 3.0	-2.26 mmHg Interval -35.0 to 11.0
Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Carbon Dioxide (pCO2) Pre-procedure (actual value)	50.30 mmHg Interval 39.2 to 67.0	52.34 mmHg Interval 24.0 to 93.0
Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Carbon Dioxide (pCO2) 24 h - post procedure (Change from pre-procedure to 24 hour post-procedure)	-6.12 mmHg Interval -35.0 to 5.0	-7.93 mmHg Interval -45.0 to 18.0
Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Carbon Dioxide (pCO2) 48 h - post procedure (Change from pre-procedure to 48 hour post-procedure)	-2.70 mmHg Interval -22.0 to 25.0	-5.64 mmHg Interval -31.0 to 18.0
Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Carbon Dioxide (pCO2) 72 h - post procedure (Change from pre-procedure to 72 hour post-procedure)	-2.92 mmHg Interval -24.0 to 19.0	-5.24 mmHg Interval -26.2 to 15.0

SECONDARY outcome

Timeframe: First 72 hours of life (1h, 6h, 24h, 48h, 72h)

Population: Intention-to-treat population (ITT): All randomized neonates who received at least one dose of study treatment.

The blood gas analysis partial pressure of oxygen (pO2) at all timepoints and the changes from pre-procedure to each timepoint are presented.

Outcome measures

Measure	Curosurf LISA n=19 Participants Single dose of poractant alfa 200 mg/kg via brief insertion of a thin catheter (CHF 6440) into the trachea in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. LISA combination product (Curosurf+catheter CHF6440): Curosurf administration through brief insertion of a thin catheter into the trachea	Curosurf Endotracheal Tube n=12 Participants Single dose of poractant alfa 200 mg/kg via the conventional intubation with endotracheal tube in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. Curosurf through conventional administration (endotracheal tube): Curosurf through conventional administration (endotracheal tube), followed by rapid extubation
Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Oxygen (pO2) Pre-procedure (actual value)	54.78 mmHg Interval 20.0 to 88.0	58.51 mmHg Interval 10.0 to 91.0
Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Oxygen (pO2) 1 h - post procedure (Change from pre-procedure to 1 hour post-procedure)	4.22 mmHg Interval -32.0 to 69.0	2.34 mmHg Interval -31.0 to 68.0
Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Oxygen (pO2) 6 h - post procedure (Change from pre-procedure to 6 hour post-procedure)	2.69 mmHg Interval -31.0 to 27.0	-0.06 mmHg Interval -67.0 to 63.0
Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Oxygen (pO2) 24 h - post procedure (Change from pre-procedure to 24 hour post-procedure)	-5.74 mmHg Interval -52.0 to 27.0	0.84 mmHg Interval -34.0 to 54.0
Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Oxygen (pO2) 48 h - post procedure (Change from pre-procedure to 48 hour post-procedure)	-7.51 mmHg Interval -37.0 to 33.0	-8.07 mmHg Interval -54.0 to 29.0
Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Oxygen (pO2) 72 h - post procedure (Change from pre-procedure to 72 hour post-procedure)	-5.01 mmHg Interval -34.1 to 52.0	-2.25 mmHg Interval -40.0 to 51.0

SECONDARY outcome

Timeframe: First 72 hours of life (1h, 6h, 24h, 48h, 72h)

Population: Intention-to-treat population (ITT): All randomized neonates who received at least one dose of study treatment.

The blood concentration of bicarbonate (HCO3^-) at all timepoints and the changes from pre-procedure to each timepoint are presented.

Outcome measures

Measure	Curosurf LISA n=19 Participants Single dose of poractant alfa 200 mg/kg via brief insertion of a thin catheter (CHF 6440) into the trachea in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. LISA combination product (Curosurf+catheter CHF6440): Curosurf administration through brief insertion of a thin catheter into the trachea	Curosurf Endotracheal Tube n=12 Participants Single dose of poractant alfa 200 mg/kg via the conventional intubation with endotracheal tube in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. Curosurf through conventional administration (endotracheal tube): Curosurf through conventional administration (endotracheal tube), followed by rapid extubation
Efficacy: Blood Analysis Parameter -- Bicarbonate (HCO3^-) 72 h - post procedure (Change from pre-procedure to 72 hour post-procedure)	-1.1 mmol/L Interval -5.0 to 5.0	0.8 mmol/L Interval -5.0 to 8.0
Efficacy: Blood Analysis Parameter -- Bicarbonate (HCO3^-) Pre-procedure (actual value)	23.4 mmol/L Interval 21.0 to 27.0	22.1 mmol/L Interval 12.0 to 27.0
Efficacy: Blood Analysis Parameter -- Bicarbonate (HCO3^-) 1 h - post procedure (Change from pre-procedure to 1 hour post-procedure)	-0.7 mmol/L Interval -2.0 to 2.0	1.1 mmol/L Interval -2.0 to 10.0
Efficacy: Blood Analysis Parameter -- Bicarbonate (HCO3^-) 6 h - post procedure (Change from pre-procedure to 6 hour post-procedure)	-1.1 mmol/L Interval -3.0 to 1.0	1.5 mmol/L Interval -7.0 to 10.0
Efficacy: Blood Analysis Parameter -- Bicarbonate (HCO3^-) 24 h - post procedure (Change from pre-procedure to 24 hour post-procedure)	-0.5 mmol/L Interval -4.0 to 4.0	0.6 mmol/L Interval -3.0 to 10.0
Efficacy: Blood Analysis Parameter -- Bicarbonate (HCO3^-) 48 h - post procedure (Change from pre-procedure to 48 hour post-procedure)	-0.9 mmol/L Interval -4.0 to 5.0	1.2 mmol/L Interval -3.0 to 10.0

SECONDARY outcome

Timeframe: First 72 hours of life (1h, 6h, 24h, 48h, 72h)

Population: Intention-to-treat population (ITT): All randomized neonates who received at least one dose of study treatment.

The blood base excess at all timepoints and the changes from pre-procedure to each timepoint are presented.

Base excess is defined as the amount of acid that must be added to each litre of fully oxygenated blood to return the pH to 7.40 at a temperature of 37°C and a pCO2 of 40 mmHg (5.3 kPa). The value is reported as a concentration in units of milliequivalent per liter (mEq/L), with positive numbers indicating an excess of base and negative a deficit.

Outcome measures

Measure	Curosurf LISA n=19 Participants Single dose of poractant alfa 200 mg/kg via brief insertion of a thin catheter (CHF 6440) into the trachea in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. LISA combination product (Curosurf+catheter CHF6440): Curosurf administration through brief insertion of a thin catheter into the trachea	Curosurf Endotracheal Tube n=12 Participants Single dose of poractant alfa 200 mg/kg via the conventional intubation with endotracheal tube in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. Curosurf through conventional administration (endotracheal tube): Curosurf through conventional administration (endotracheal tube), followed by rapid extubation
Efficacy: Blood Analysis Parameter -- Base Excess Pre-procedure (actual value)	-3.20 mEq/L Interval -6.5 to 1.3	-5.22 mEq/L Interval -15.6 to 3.0
Efficacy: Blood Analysis Parameter -- Base Excess 1 h - post procedure (Change from pre-procedure to 1 hour post-procedure)	-0.49 mEq/L Interval -2.5 to 1.7	1.07 mEq/L Interval -3.0 to 11.1
Efficacy: Blood Analysis Parameter -- Base Excess 6 h - post procedure (Change from pre-procedure to 6 hour post-procedure)	-0.10 mEq/L Interval -2.4 to 2.1	1.61 mEq/L Interval -5.0 to 10.9
Efficacy: Blood Analysis Parameter -- Base Excess 24 h - post procedure (Change from pre-procedure to 24 hour post-procedure)	0.16 mEq/L Interval -2.7 to 3.1	2.17 mEq/L Interval -5.0 to 15.9
Efficacy: Blood Analysis Parameter -- Base Excess 48 h - post procedure (Change from pre-procedure to 48 hour post-procedure)	-0.29 mEq/L Interval -3.8 to 2.6	3.21 mEq/L Interval -2.0 to 13.2
Efficacy: Blood Analysis Parameter -- Base Excess 72 h - post procedure (Change from pre-procedure to 72 hour post-procedure)	-0.97 mEq/L Interval -5.1 to 4.0	2.37 mEq/L Interval -4.0 to 10.7

SECONDARY outcome

Timeframe: First 72 hours of life (1h, 6h, 24h, 48h, 72h)

Population: Intention-to-treat population (ITT): All randomized neonates who received at least one dose of study treatment.

The blood concentration of lactate at all timepoints and the changes from pre-procedure to each timepoint are presented.

Outcome measures

Measure	Curosurf LISA n=19 Participants Single dose of poractant alfa 200 mg/kg via brief insertion of a thin catheter (CHF 6440) into the trachea in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. LISA combination product (Curosurf+catheter CHF6440): Curosurf administration through brief insertion of a thin catheter into the trachea	Curosurf Endotracheal Tube n=12 Participants Single dose of poractant alfa 200 mg/kg via the conventional intubation with endotracheal tube in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. Curosurf through conventional administration (endotracheal tube): Curosurf through conventional administration (endotracheal tube), followed by rapid extubation
Efficacy: Blood Analysis Parameter -- Lactate 48 h - post procedure (Change from pre-procedure to 48 hour post-procedure)	-0.284 mmol/L Interval -1.4 to 1.2	-2.168 mmol/L Interval -8.3 to 0.5
Efficacy: Blood Analysis Parameter -- Lactate Pre-procedure (actual value)	2.047 mmol/L Interval 1.16 to 3.38	2.825 mmol/L Interval 0.6 to 10.5
Efficacy: Blood Analysis Parameter -- Lactate 1 h - post procedure (Change from pre-procedure to 1 hour post-procedure)	0.311 mmol/L Interval -0.2 to 1.28	-0.188 mmol/L Interval -1.4 to 0.6
Efficacy: Blood Analysis Parameter -- Lactate 6 h - post procedure (Change from pre-procedure to 6 hour post-procedure)	0.425 mmol/L Interval -0.5 to 1.03	-0.802 mmol/L Interval -7.6 to 1.09
Efficacy: Blood Analysis Parameter -- Lactate 24 h - post procedure (Change from pre-procedure to 24 hour post-procedure)	0.009 mmol/L Interval -0.3 to 0.56	-1.100 mmol/L Interval -8.5 to 0.7
Efficacy: Blood Analysis Parameter -- Lactate 72 h - post procedure (Change from pre-procedure to 72 hour post-procedure)	-0.418 mmol/L Interval -1.77 to 0.7	-1.656 mmol/L Interval -8.1 to 0.5

Adverse Events

Curosurf LISA

Serious events: 1 serious events

Other events: 19 other events

Deaths: 1 deaths

Curosurf Endotracheal Tube

Serious events: 2 serious events

Other events: 12 other events

Deaths: 1 deaths

Serious adverse events

Measure	Curosurf LISA n=19 participants at risk Single dose of poractant alfa 200 mg/kg via brief insertion of a thin catheter (CHF 6440) into the trachea in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. LISA combination product (Curosurf+catheter CHF6440): Curosurf administration through brief insertion of a thin catheter into the trachea	Curosurf Endotracheal Tube n=12 participants at risk Single dose of poractant alfa 200 mg/kg via the conventional intubation with endotracheal tube in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. Curosurf through conventional administration (endotracheal tube): Curosurf through conventional administration (endotracheal tube), followed by rapid extubation
Cardiac disorders Cardio-respiratory arrest	0.00% 0/19 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	8.3% 1/12 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Cardiac disorders Cardiopulmonary failure	0.00% 0/19 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	8.3% 1/12 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Infections and infestations Fungal sepsis	5.3% 1/19 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	0.00% 0/12 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Injury, poisoning and procedural complications Subdural haematoma	5.3% 1/19 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	0.00% 0/12 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Nervous system disorders Intraventricular haemorrhage neonatal	0.00% 0/19 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	8.3% 1/12 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage neonatal	0.00% 0/19 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	8.3% 1/12 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.

Other adverse events

Measure	Curosurf LISA n=19 participants at risk Single dose of poractant alfa 200 mg/kg via brief insertion of a thin catheter (CHF 6440) into the trachea in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. LISA combination product (Curosurf+catheter CHF6440): Curosurf administration through brief insertion of a thin catheter into the trachea	Curosurf Endotracheal Tube n=12 participants at risk Single dose of poractant alfa 200 mg/kg via the conventional intubation with endotracheal tube in neonates with RDS. A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed. After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed. Curosurf through conventional administration (endotracheal tube): Curosurf through conventional administration (endotracheal tube), followed by rapid extubation
Blood and lymphatic system disorders Anaemia neonatal	52.6% 10/19 • Number of events 10 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	33.3% 4/12 • Number of events 4 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Blood and lymphatic system disorders Thrombocytopenia neonatal	10.5% 2/19 • Number of events 2 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	8.3% 1/12 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Cardiac disorders Bradycardia neonatal	36.8% 7/19 • Number of events 8 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	8.3% 1/12 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Cardiac disorders Neonatal tachycardia	10.5% 2/19 • Number of events 2 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	16.7% 2/12 • Number of events 2 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Cardiac disorders Supraventricular extrasystoles	5.3% 1/19 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	0.00% 0/12 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Congenital, familial and genetic disorders Hydrocele	5.3% 1/19 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	0.00% 0/12 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Cardiac disorders Patent ductus arteriosus	31.6% 6/19 • Number of events 6 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	41.7% 5/12 • Number of events 5 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Eye disorders Retinopathy of prematurity	36.8% 7/19 • Number of events 7 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	33.3% 4/12 • Number of events 5 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Gastrointestinal disorders Abdominal distension	5.3% 1/19 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	8.3% 1/12 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Gastrointestinal disorders Constipation	5.3% 1/19 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	0.00% 0/12 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Gastrointestinal disorders Gastrooesophageal reflux disease	5.3% 1/19 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	8.3% 1/12 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Gastrointestinal disorders Ileus	5.3% 1/19 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	0.00% 0/12 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Gastrointestinal disorders Inguinal hernia	5.3% 1/19 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	0.00% 0/12 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Gastrointestinal disorders Umbilical hernia	0.00% 0/19 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	8.3% 1/12 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Gastrointestinal disorders Vomiting	5.3% 1/19 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	0.00% 0/12 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
General disorders Oedema neonatal	5.3% 1/19 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	0.00% 0/12 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Hepatobiliary disorders Hyperbilirubinaemia neonatal	57.9% 11/19 • Number of events 11 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	41.7% 5/12 • Number of events 5 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Hepatobiliary disorders Neonatal cholestasis	10.5% 2/19 • Number of events 2 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	0.00% 0/12 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Infections and infestations Bacteraemia	5.3% 1/19 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	0.00% 0/12 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Infections and infestations Cellulitis	5.3% 1/19 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	0.00% 0/12 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Infections and infestations Conjunctivitis	0.00% 0/19 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	8.3% 1/12 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Infections and infestations Periumbilical abscess	0.00% 0/19 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	8.3% 1/12 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Infections and infestations Sepsis neonatal	0.00% 0/19 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	16.7% 2/12 • Number of events 3 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Infections and infestations Staphylococcal bacteraemia	5.3% 1/19 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	8.3% 1/12 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Infections and infestations Staphylococcal infection	5.3% 1/19 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	16.7% 2/12 • Number of events 2 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Infections and infestations Urinary tract infection bacterial	0.00% 0/19 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	8.3% 1/12 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Infections and infestations Urinary tract infection neonatal	15.8% 3/19 • Number of events 4 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	8.3% 1/12 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Investigations Blood creatinine increased	0.00% 0/19 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	16.7% 2/12 • Number of events 2 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Investigations C-reactive protein increased	10.5% 2/19 • Number of events 2 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	0.00% 0/12 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Investigations Cardiac murmur	0.00% 0/19 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	8.3% 1/12 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Investigations Heart rate decreased	5.3% 1/19 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	0.00% 0/12 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Metabolism and nutrition disorders Alkalosis	0.00% 0/19 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	8.3% 1/12 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Metabolism and nutrition disorders Feeding intolerance	5.3% 1/19 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	0.00% 0/12 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Metabolism and nutrition disorders Hyperglycaemia	5.3% 1/19 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	0.00% 0/12 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/19 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	8.3% 1/12 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Metabolism and nutrition disorders Hypermagnesaemia	5.3% 1/19 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	16.7% 2/12 • Number of events 2 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Metabolism and nutrition disorders Hypokalaemia	10.5% 2/19 • Number of events 2 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	0.00% 0/12 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Metabolism and nutrition disorders Metabolic acidosis	5.3% 1/19 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	0.00% 0/12 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Metabolism and nutrition disorders Neonatal hypocalcaemia	5.3% 1/19 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	8.3% 1/12 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Metabolism and nutrition disorders Neonatal hyponatraemia	21.1% 4/19 • Number of events 5 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	8.3% 1/12 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Metabolism and nutrition disorders Poor feeding infant	10.5% 2/19 • Number of events 2 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	0.00% 0/12 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Acquired plagiocephaly	5.3% 1/19 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	0.00% 0/12 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Haemangioma	5.3% 1/19 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	0.00% 0/12 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Nervous system disorders Cerebral ventricle dilatation	5.3% 1/19 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	0.00% 0/12 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Nervous system disorders Intraventricular haemorrhage neonatal	21.1% 4/19 • Number of events 5 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	8.3% 1/12 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Nervous system disorders Periventricular leukomalacia	0.00% 0/19 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	8.3% 1/12 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Pregnancy, puerperium and perinatal conditions Jaundice neonatal	10.5% 2/19 • Number of events 2 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	0.00% 0/12 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Product Issues Device occlusion	5.3% 1/19 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	0.00% 0/12 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Renal and urinary disorders Acute kidney injury	5.3% 1/19 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	0.00% 0/12 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Bronchopulmonary dysplasia	47.4% 9/19 • Number of events 9 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	41.7% 5/12 • Number of events 5 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Chronic respiratory disease	5.3% 1/19 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	0.00% 0/12 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Infantile apnoea	68.4% 13/19 • Number of events 13 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	41.7% 5/12 • Number of events 5 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Laryngeal haemorrhage	5.3% 1/19 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	0.00% 0/12 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Lung disorder	5.3% 1/19 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	0.00% 0/12 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/19 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	8.3% 1/12 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Neonatal hypoxia	36.8% 7/19 • Number of events 8 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	33.3% 4/12 • Number of events 4 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Neonatal respiratory failure	5.3% 1/19 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	8.3% 1/12 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Neonatal tachypnoea	5.3% 1/19 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	0.00% 0/12 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	5.3% 1/19 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	0.00% 0/12 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage neonatal	10.5% 2/19 • Number of events 2 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	0.00% 0/12 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary interstitial emphysema syndrome	5.3% 1/19 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	0.00% 0/12 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Respiration abnormal	5.3% 1/19 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	0.00% 0/12 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Skin disorder	10.5% 2/19 • Number of events 3 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	0.00% 0/12 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.
Vascular disorders Hypertension neonatal	0.00% 0/19 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.	8.3% 1/12 • Number of events 1 • Adverse events (AEs) and serious AEs (SAEs) that started on or after the date of first randomized treatment administration up to the end of the main phase of the study. The main phase of the study included all time points from the pre-randomization period up to and including the follow-up visit at discharge home or 40 weeks PMA, whichever came first. An AE: defined as "any untoward medical occurrence in a neonate or clinical trial neonate who received the study drug and which did not necessarily have a causal relationship with this treatment", whether or not considered related to the investigational product. Safety population (SAF) was used for the analysis of safety. SAF: all randomized neonates who received at least one dose of study treatment.

Additional Information

Clinical Trial Transparency

Chiesi Farmaceutici S.p.A.

Phone: + 39 0521 2791

Email: clinicaltrials_info@chiesi.com

Results disclosure agreements

• Principal investigator is a sponsor employee Chiesi can publish and/or present any results of this study at scientific meetings, and to submit the clinical trial data to national and international Regulatory Authorities. Chiesi reserves the right to use such data for industrial purposes. Investigators will inform Chiesi before using the results of the study for publication or presentation, and agree to provide the Sponsor with a copy of the proposed presentation. Data from individual study sites must not be published separately.
• Publication restrictions are in place

Restriction type: OTHER