Trial Outcomes & Findings for Poractant Alfa (Curosurf®)) -- Effect in Adult Patients Diagnosed With 2019 Novel Coronavirus (SARS-COV-19; (Covid-19)) Acute Respiratory Distress Syndrome (ARDS) (NCT NCT04502433)

Last Updated: 2023-06-23

Results Overview

The number of days alive and ventilator-free days, defined as the number of days the patient is not receiving mechanical ventilation over the 21 days following randomisation. Mechanical ventilation was defined as invasive and non-invasive. The patient was defined as free of mechanical ventilation after 12 hours from the suspension of either invasive and non-invasive ventilation. Patients who died or were mechanically ventilated longer than this period were assessed as zero ventilator-free days.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

22 participants

Primary outcome timeframe

up to 21 days

Results posted on

2023-06-23

Participant Flow

The planned 70 randomised patients in a 3:2 ratio, according to the inclusion and exclusion criteria. This was not achieved; owing to a global improvement in the pandemic situation in the countries where the study was performed (Italy, UK, US), patient recruitment was lower than expected (i.e. 22 patients were randomised, 14 patients and 8 patients in the poractant alfa and control groups, respectively); the study was terminated early before reaching the target sample size.

Participant milestones

Participant milestones
Measure	Control Cohort Patients receiving standard-of-care (SoC)	Poractant Alfa Treated Cohort Patients treated with CUROSURF® (poractant alfa), as an add-on to standard-of-care (SoC)
Overall Study STARTED	8	14
Overall Study COMPLETED	5	9
Overall Study NOT COMPLETED	3	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Control Cohort Patients receiving standard-of-care (SoC)	Poractant Alfa Treated Cohort Patients treated with CUROSURF® (poractant alfa), as an add-on to standard-of-care (SoC)
Overall Study Death	2	4
Overall Study Lost to Follow-up	1	0
Overall Study Physician Decision	0	1

Baseline Characteristics

Poractant Alfa (Curosurf®)) -- Effect in Adult Patients Diagnosed With 2019 Novel Coronavirus (SARS-COV-19; (Covid-19)) Acute Respiratory Distress Syndrome (ARDS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Control Cohort n=8 Participants Patients receiving SoC	Poractant Alfa Treated Cohort n=13 Participants Patients treated with CUROSURF® (poractant alfa), as an add-on to standard-of-care (SoC)	Total n=21 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants
Age, Continuous	51.0 years STANDARD_DEVIATION 18.2 • n=5 Participants	63.6 years STANDARD_DEVIATION 9.2 • n=7 Participants	58.8 years STANDARD_DEVIATION 14.4 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	10 Participants n=7 Participants	16 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	12 Participants n=7 Participants	18 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Body mass index (BMI)	36.44 kg/m^2 STANDARD_DEVIATION 9.90 • n=5 Participants	29.78 kg/m^2 STANDARD_DEVIATION 5.05 • n=7 Participants	32.32 kg/m^2 STANDARD_DEVIATION 7.78 • n=5 Participants
Arterial Partial Pressure of Oxygen/Fraction of inspired oxygen (PaO2/FiO2) ratio	109.70 Ratio STANDARD_DEVIATION 51.15 • n=5 Participants	111.85 Ratio STANDARD_DEVIATION 38.72 • n=7 Participants	111.03 Ratio STANDARD_DEVIATION 42.62 • n=5 Participants
Fraction of inspired oxygen (FiO2)	70.5 percentage of inspired oxygen STANDARD_DEVIATION 18.1 • n=5 Participants	65.0 percentage of inspired oxygen STANDARD_DEVIATION 23.2 • n=7 Participants	67.1 percentage of inspired oxygen STANDARD_DEVIATION 21.1 • n=5 Participants
Sequential Organ Failure Assessment (SOFA) score	7.0 score STANDARD_DEVIATION 3.5 • n=5 Participants	7.8 score STANDARD_DEVIATION 4.6 • n=7 Participants	7.5 score STANDARD_DEVIATION 4.2 • n=5 Participants

PRIMARY outcome

Timeframe: up to 21 days

Population: Intention-to-Treat (ITT) population: all randomised patients who had at least one available evaluation of efficacy after baseline. Data was summarised by treatment group using, descriptive statistics. Due to low recruitment rate the study was terminated early for non-safety reasons.

Outcome measures

Outcome measures
Measure	Control Cohort n=8 Participants Patients receiving standard-of-care (SoC)	Poractant Alfa Treated Cohort n=13 Participants Patients treated with CUROSURF® (poractant alfa), as an add-on to standard-of-care (SoC)
Number of Days Alive and Ventilator-free Days	4.8 days Standard Deviation 6.6	1.2 days Standard Deviation 4.2

SECONDARY outcome

Timeframe: at Day 28

The percentage of patients alive and free of respiratory failure (i.e. without need for mechanical ventilation, extracorporeal membrane oxygenation (ECMO), non-invasive ventilation, or high-flow nasal cannula oxygen delivery) at Day 28.

Outcome measures

Outcome measures
Measure	Control Cohort n=8 Participants Patients receiving standard-of-care (SoC)	Poractant Alfa Treated Cohort n=13 Participants Patients treated with CUROSURF® (poractant alfa), as an add-on to standard-of-care (SoC)
Percentage of Patients Alive and Free of Respiratory Failure at Day 28	25.0 percentage of participants	15.4 percentage of participants

SECONDARY outcome

Timeframe: at Day 28

The number of days alive and ventilator-free (i.e. free of any mechanical ventilation for at least 12 hours) at Day 28.

Outcome measures

Outcome measures
Measure	Control Cohort n=8 Participants Patients receiving standard-of-care (SoC)	Poractant Alfa Treated Cohort n=13 Participants Patients treated with CUROSURF® (poractant alfa), as an add-on to standard-of-care (SoC)
Number of Days Alive and Ventilator-Free at Day 28	7.4 days Standard Deviation 10.2	1.7 days Standard Deviation 6.1

SECONDARY outcome

Timeframe: at Day 21 and at Day 28

Mortality at Day 21 and Day 28 of the study by treatment group.

Outcome measures

Outcome measures
Measure	Control Cohort n=8 Participants Patients receiving standard-of-care (SoC)	Poractant Alfa Treated Cohort n=13 Participants Patients treated with CUROSURF® (poractant alfa), as an add-on to standard-of-care (SoC)
Mortality at Day 21 and Day 28 Dead at Day 21	2 Participants	4 Participants
Mortality at Day 21 and Day 28 Dead at Day 28	2 Participants	4 Participants

SECONDARY outcome

Timeframe: Day 21 and Day 28

The number of days alive and free from invasive ventilation at Day 21 and Day 28 is presented by treatment group.

Outcome measures

Outcome measures
Measure	Control Cohort n=8 Participants Patients receiving standard-of-care (SoC)	Poractant Alfa Treated Cohort n=13 Participants Patients treated with CUROSURF® (poractant alfa), as an add-on to standard-of-care (SoC)
Number of Days Alive and Free From Invasive Ventilation at Day 21 and Day 28 Days alive and free from invasive ventilation at Day 21	0 days Interval 0.0 to 15.0	0 days Interval 0.0 to 15.0
Number of Days Alive and Free From Invasive Ventilation at Day 21 and Day 28 Days alive and free from invasive ventilation at Day 28	0 days Interval 0.0 to 22.0	0 days Interval 0.0 to 22.0

SECONDARY outcome

Timeframe: Day 21 and Day 28

The number of days alive and free from non-invasive ventilation at Day 21 and Day 28 is presented by treatment group.

Outcome measures

Outcome measures
Measure	Control Cohort n=8 Participants Patients receiving standard-of-care (SoC)	Poractant Alfa Treated Cohort n=13 Participants Patients treated with CUROSURF® (poractant alfa), as an add-on to standard-of-care (SoC)
Number of Days Alive and Free From Non-Invasive Ventilation at Day 21 and Day 28 Days alive and free from non-invasive ventilation at Day 21	12.5 days Interval 0.0 to 21.0	21.0 days Interval 0.0 to 21.0
Number of Days Alive and Free From Non-Invasive Ventilation at Day 21 and Day 28 Days alive and free from non-invasive ventilation at Day 28	19.5 days Interval 0.0 to 28.0	28.0 days Interval 0.0 to 28.0

SECONDARY outcome

Timeframe: Day 28 or Discharge, whichever comes first

The severity status of patients at baseline and at Day 28/Discharge and the percentage of patients with improvement in severity status (i.e. a decrease of at least 1 point in severity status) at Day 28/Discharge relative to baseline is presented. Severity was assessed using a point score system: Severity score was defined as mild, moderate, severe (see below\*), or death and was based on PaO2/FiO2 ratio and patient status at Day 28/Discharge and numerically rated from 1-4, respectively. An improvement in severity was defined as a decrease of at least 1 point between baseline and Day 28/Discharge. At Day 28 the last follow up evaluation took place on the ICU if, still requiring critical care, or by phone call if the patient has been discharged from ICU by that time. \*Mild: 200 mmHg \< PaO2/FiO2 ratio ≤300 mmHg; Moderate: 100 mmHg \< PaO2/FiO2 ratio ≤200 mmHg; Severe: PaO2/FiO2 ratio ≤100 mmHg

Outcome measures

Outcome measures
Measure	Control Cohort n=6 Participants Patients receiving standard-of-care (SoC)	Poractant Alfa Treated Cohort n=12 Participants Patients treated with CUROSURF® (poractant alfa), as an add-on to standard-of-care (SoC)
Percentage of Patients With Improvement in Severity Status at Day 28 or Discharge (Severity Score: Mild, Moderate, Severe, or Death)	50.0 percentage of participants	25.0 percentage of participants

SECONDARY outcome

Timeframe: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28

Change from baseline in PaO2/FiO2 ratio measured at each timepoint following administration of each dose in the treatment and control group. The change was calculated from two time points as the value at the later time point minus the value at baseline. Partial pressure of oxygen (PaO2) is the oxygen pressure in arterial blood. The fraction of inspired oxygen (FiO2) is the concentration of oxygen in the gas mixture. The fraction of inspired oxygen (PaO2/FiO2) ratio is widely used in ICUs as an indicator of oxygenation status.

Outcome measures

Outcome measures
Measure	Control Cohort n=8 Participants Patients receiving standard-of-care (SoC)	Poractant Alfa Treated Cohort n=13 Participants Patients treated with CUROSURF® (poractant alfa), as an add-on to standard-of-care (SoC)
Change From Baseline in Arterial Partial Pressure of Oxygen / Fraction of Inspired Oxygen (PaO2/FiO2) Ratio at Each Timepoint 6 hours	7.00 mmHg Interval -53.5 to 197.08	13.00 mmHg Interval -67.5 to 67.51
Change From Baseline in Arterial Partial Pressure of Oxygen / Fraction of Inspired Oxygen (PaO2/FiO2) Ratio at Each Timepoint 12 hours	23.00 mmHg Interval -60.58 to 220.0	10.01 mmHg Interval -60.0 to 82.51
Change From Baseline in Arterial Partial Pressure of Oxygen / Fraction of Inspired Oxygen (PaO2/FiO2) Ratio at Each Timepoint 24 hours	31.00 mmHg Interval -69.42 to 235.0	2.36 mmHg Interval -57.01 to 67.0
Change From Baseline in Arterial Partial Pressure of Oxygen / Fraction of Inspired Oxygen (PaO2/FiO2) Ratio at Each Timepoint 30 hours	70.00 mmHg Interval -104.92 to 182.0	10.00 mmHg Interval -41.02 to 143.0
Change From Baseline in Arterial Partial Pressure of Oxygen / Fraction of Inspired Oxygen (PaO2/FiO2) Ratio at Each Timepoint 36 hours	11.00 mmHg Interval -103.8 to 203.0	31.00 mmHg Interval -35.4 to 165.02
Change From Baseline in Arterial Partial Pressure of Oxygen / Fraction of Inspired Oxygen (PaO2/FiO2) Ratio at Each Timepoint 48 hours	24.00 mmHg Interval -83.11 to 183.0	15.65 mmHg Interval -38.0 to 89.0
Change From Baseline in Arterial Partial Pressure of Oxygen / Fraction of Inspired Oxygen (PaO2/FiO2) Ratio at Each Timepoint 54 hours	78.00 mmHg Interval -132.19 to 304.0	25.07 mmHg Interval -54.61 to 98.0
Change From Baseline in Arterial Partial Pressure of Oxygen / Fraction of Inspired Oxygen (PaO2/FiO2) Ratio at Each Timepoint 60 hours	0.00 mmHg Interval -103.06 to 308.0	7.00 mmHg Interval -56.0 to 120.01
Change From Baseline in Arterial Partial Pressure of Oxygen / Fraction of Inspired Oxygen (PaO2/FiO2) Ratio at Each Timepoint 72 hours	-1.40 mmHg Interval -39.41 to 278.0	-1.00 mmHg Interval -41.85 to 67.0
Change From Baseline in Arterial Partial Pressure of Oxygen / Fraction of Inspired Oxygen (PaO2/FiO2) Ratio at Each Timepoint 28 day	53.50 mmHg Interval -21.0 to 128.0	20.00 mmHg Interval -93.45 to 135.02

SECONDARY outcome

Timeframe: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28

The percentages of patients in categories of PaO2/FiO2 ratio improvement compared to baseline (\>20%) at all timepoints post-baseline are summarised by treatment group.

Outcome measures

Outcome measures
Measure	Control Cohort n=8 Participants Patients receiving standard-of-care (SoC)	Poractant Alfa Treated Cohort n=13 Participants Patients treated with CUROSURF® (poractant alfa), as an add-on to standard-of-care (SoC)
Percentage of Patients Alive and With PaO2/FiO2 Ratio Improvement >20% Compared to Baseline at Each Timepoint 6 hours	37.5 percentage of participants	46.2 percentage of participants
Percentage of Patients Alive and With PaO2/FiO2 Ratio Improvement >20% Compared to Baseline at Each Timepoint 12 hours	62.5 percentage of participants	41.7 percentage of participants
Percentage of Patients Alive and With PaO2/FiO2 Ratio Improvement >20% Compared to Baseline at Each Timepoint 24 hours	50.0 percentage of participants	38.5 percentage of participants
Percentage of Patients Alive and With PaO2/FiO2 Ratio Improvement >20% Compared to Baseline at Each Timepoint 30 hours	57.1 percentage of participants	38.5 percentage of participants
Percentage of Patients Alive and With PaO2/FiO2 Ratio Improvement >20% Compared to Baseline at Each Timepoint 36 hours	50.0 percentage of participants	53.8 percentage of participants
Percentage of Patients Alive and With PaO2/FiO2 Ratio Improvement >20% Compared to Baseline at Each Timepoint 48 hours	50.0 percentage of participants	46.2 percentage of participants
Percentage of Patients Alive and With PaO2/FiO2 Ratio Improvement >20% Compared to Baseline at Each Timepoint 54 hours	71.4 percentage of participants	58.3 percentage of participants
Percentage of Patients Alive and With PaO2/FiO2 Ratio Improvement >20% Compared to Baseline at Each Timepoint 60 hours	28.6 percentage of participants	38.5 percentage of participants
Percentage of Patients Alive and With PaO2/FiO2 Ratio Improvement >20% Compared to Baseline at Each Timepoint 72 hours	14.3 percentage of participants	33.3 percentage of participants
Percentage of Patients Alive and With PaO2/FiO2 Ratio Improvement >20% Compared to Baseline at Each Timepoint 28 day	25.0 percentage of participants	27.3 percentage of participants

SECONDARY outcome

Timeframe: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28

The FiO2 at baseline and at selected timepoints post-baseline was measured. Results are shown as changes from baseline, summarised by treatment group. The change was calculated from two time points as the value at the later time point minus the value at baseline. The unit for the variable is percent (%) and what is reported is an absolute change.

Outcome measures

Outcome measures
Measure	Control Cohort n=8 Participants Patients receiving standard-of-care (SoC)	Poractant Alfa Treated Cohort n=13 Participants Patients treated with CUROSURF® (poractant alfa), as an add-on to standard-of-care (SoC)
Change From Baseline in Fraction of Inspired Oxygen (FiO2) at Each Timepoint 6 hours	-7.2 percent (absolute change) Interval -30.0 to 20.0	0.0 percent (absolute change) Interval -35.0 to 20.0
Change From Baseline in Fraction of Inspired Oxygen (FiO2) at Each Timepoint 12 hours	-2.5 percent (absolute change) Interval -25.0 to 20.0	-5.0 percent (absolute change) Interval -50.0 to 15.0
Change From Baseline in Fraction of Inspired Oxygen (FiO2) at Each Timepoint 24 hours	0.0 percent (absolute change) Interval -30.0 to 15.0	0.0 percent (absolute change) Interval -45.0 to 55.0
Change From Baseline in Fraction of Inspired Oxygen (FiO2) at Each Timepoint 30 hours	-15.0 percent (absolute change) Interval -30.0 to 5.7	-5.0 percent (absolute change) Interval -50.0 to 25.0
Change From Baseline in Fraction of Inspired Oxygen (FiO2) at Each Timepoint 36 hours	-10.0 percent (absolute change) Interval -30.0 to 15.0	-10.0 percent (absolute change) Interval -50.0 to 10.0
Change From Baseline in Fraction of Inspired Oxygen (FiO2) at Each Timepoint 48 hours	-12.5 percent (absolute change) Interval -35.0 to 45.7	0.0 percent (absolute change) Interval -55.0 to 55.0
Change From Baseline in Fraction of Inspired Oxygen (FiO2) at Each Timepoint 54 hours	-12.5 percent (absolute change) Interval -50.0 to 15.7	-5.0 percent (absolute change) Interval -55.0 to 50.0
Change From Baseline in Fraction of Inspired Oxygen (FiO2) at Each Timepoint 60 hours	2.5 percent (absolute change) Interval -40.0 to 20.0	-5.0 percent (absolute change) Interval -60.0 to 20.0
Change From Baseline in Fraction of Inspired Oxygen (FiO2) at Each Timepoint 72 hours	-4.9 percent (absolute change) Interval -50.0 to 10.0	0.0 percent (absolute change) Interval -55.0 to 50.0
Change From Baseline in Fraction of Inspired Oxygen (FiO2) at Each Timepoint 28 day	-14.3 percent (absolute change) Interval -60.0 to 10.0	-7.5 percent (absolute change) Interval -60.0 to 50.0

SECONDARY outcome

Timeframe: up to 28 days

The length of ICU stay (days) at Day 28 is presented by treatment by treatment group. Patients who died or were mechanically ventilated longer than this period were assigned with 28 days.

Outcome measures

Outcome measures
Measure	Control Cohort n=8 Participants Patients receiving standard-of-care (SoC)	Poractant Alfa Treated Cohort n=13 Participants Patients treated with CUROSURF® (poractant alfa), as an add-on to standard-of-care (SoC)
Length of ICU Stay (Days) at Day 28	28.0 days Interval 9.0 to 28.0	28.0 days Interval 12.0 to 28.0

SECONDARY outcome

Timeframe: Day 28

The percentage of patients alive and out of ICU at Day 28 is presented by treatment group.

Outcome measures

Outcome measures
Measure	Control Cohort n=8 Participants Patients receiving standard-of-care (SoC)	Poractant Alfa Treated Cohort n=13 Participants Patients treated with CUROSURF® (poractant alfa), as an add-on to standard-of-care (SoC)
Percentage of Patients Alive and Out of Intensive Care Unit (ICU) at Day 28	37.5 percentage of participants	7.7 percentage of participants

SECONDARY outcome

Timeframe: Day 3 and Day 28 or discharge -- whichever comes first

The Sequential Organ Failure Assessment (SOFA) score is a scoring system that assesses the performance of several organ systems in the body. The SOFA score was used to determine the extent of organ failure at Day 3 and Day 28/Discharge with respect to a pre-randomisation assessment. The total score was derived from six sub-scores system categories: respiratory, neurological, cardiovascular, hepatic, coagulation, and renal systems; respective sub-scores were calculated primarily considering PaO2/FiO2 ratio, Glasgow Coma Scale, mean arterial pressure (MAP) or requirement for vasopressor administration, bilirubin levels, platelet levels and creatinine levels or daily urine output. A score of 0, 1, 2, 3, or 4) was assigned to each of the six system category. The total score ranged from 0 (min) to 24 (max) points. To be considered organ failure free, a patient had to have a score of 0.

Outcome measures

Outcome measures
Measure	Control Cohort n=8 Participants Patients receiving standard-of-care (SoC)	Poractant Alfa Treated Cohort n=13 Participants Patients treated with CUROSURF® (poractant alfa), as an add-on to standard-of-care (SoC)
Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 SOFA score -- Day 3	0.5 score on a scale Interval -5.0 to 5.0	0.0 score on a scale Interval -5.0 to 5.0
Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 SOFA score -- Day 28 / Discharge	-1.0 score on a scale Interval -6.0 to 11.0	0.0 score on a scale Interval -4.0 to 2.0
Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 Respiratory system score -- Day 3	0.0 score on a scale Interval -1.0 to 1.0	0.0 score on a scale Interval -1.0 to 1.0
Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 Respiratory system score -- Day 28 / Discharge	-1.0 score on a scale Interval -1.0 to 0.0	-0.5 score on a scale Interval -1.0 to 1.0
Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 Neurological system score -- Day 3	0.0 score on a scale Interval -4.0 to 2.0	0.0 score on a scale Interval 0.0 to 1.0
Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 Neurological system score -- Day 28 / Discharge	-2.0 score on a scale Interval -4.0 to 2.0	0.0 score on a scale Interval -3.0 to 0.0
Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 Cardiovascular system score -- Day 3	0.0 score on a scale Interval -1.0 to 1.0	0.0 score on a scale Interval -3.0 to 3.0
Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 Cardiovascular system score -- Day 28 / Discharge	0.0 score on a scale Interval -1.0 to 3.0	0.0 score on a scale Interval -2.0 to 1.0
Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 Hepatic system score -- Day 3	0.0 score on a scale Interval -1.0 to 0.0	0.0 score on a scale Interval -2.0 to 2.0
Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 Hepatic system score -- Day 28 / Discharge	0.0 score on a scale Interval 0.0 to 1.0	0.0 score on a scale Interval 0.0 to 0.0
Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 Coagulatory system score -- Day 3	0.0 score on a scale Interval -1.0 to 1.0	0.0 score on a scale Interval -1.0 to 1.0
Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 Coagulatory system score -- Day 28 / Discharge	0.0 score on a scale Interval -1.0 to 3.0	0.0 score on a scale Interval -1.0 to 1.0
Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 Renal system score -- Day 3	0.0 score on a scale Interval 0.0 to 4.0	0.0 score on a scale Interval 0.0 to 2.0
Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 Renal system score -- Day 28 / Discharge	0.0 score on a scale Interval 0.0 to 2.0	0.0 score on a scale Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: at day 28 or discharge -- whichever comes first

The percentage of patients alive and organ failure free (defined as SOFA score=0) at Day 28/Discharge is presented by treatment group. The total score was derived from six sub-scores system categories: respiratory, neurological, cardiovascular, hepatic, coagulation, and renal systems; respective sub-scores were calculated primarily considering PaO2/FiO2 ratio, Glasgow Coma Scale, mean arterial pressure (MAP) or requirement for vasopressor administration, bilirubin levels, platelet levels and creatinine levels or daily urine output. A score of 0, 1, 2, 3, or 4) was assigned to each of the six system category. The total score ranged from 0 (min) to 24 (max) points. To be considered organ failure free, a patient had to have a score of 0.

Outcome measures

Outcome measures
Measure	Control Cohort n=8 Participants Patients receiving standard-of-care (SoC)	Poractant Alfa Treated Cohort n=13 Participants Patients treated with CUROSURF® (poractant alfa), as an add-on to standard-of-care (SoC)
Percentage of Patients Alive and Free of Organ Failure (SOFA Score=0)	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28

Ventilatory parameter: Change from baseline in tidal volume (mL/kg BW) at all timepoints up to Day 3 (72 hours) and at Day 28. The change was calculated from two time points as the value at the later time point minus the value at baseline. Tidal volume is the amount of air that moves in or out of the lungs with each respiratory cycle.

Outcome measures

Outcome measures
Measure	Control Cohort n=8 Participants Patients receiving standard-of-care (SoC)	Poractant Alfa Treated Cohort n=13 Participants Patients treated with CUROSURF® (poractant alfa), as an add-on to standard-of-care (SoC)
Ventilatory Parameter: Tidal Volume -- Change From Baseline in Tidal Volume (mL/kg BW) at All Timepoints up to Day 3 (72 Hours) and at Day 28 6 hours	1.50 mL/kg BW Interval -101.0 to 152.0	-1.00 mL/kg BW Interval -90.0 to 93.0
Ventilatory Parameter: Tidal Volume -- Change From Baseline in Tidal Volume (mL/kg BW) at All Timepoints up to Day 3 (72 Hours) and at Day 28 12 hours	4.50 mL/kg BW Interval -67.0 to 194.0	13.00 mL/kg BW Interval -170.0 to 129.0
Ventilatory Parameter: Tidal Volume -- Change From Baseline in Tidal Volume (mL/kg BW) at All Timepoints up to Day 3 (72 Hours) and at Day 28 24 hours	15.00 mL/kg BW Interval -252.0 to 166.0	0.00 mL/kg BW Interval -170.0 to 147.0
Ventilatory Parameter: Tidal Volume -- Change From Baseline in Tidal Volume (mL/kg BW) at All Timepoints up to Day 3 (72 Hours) and at Day 28 30 hours	61.00 mL/kg BW Interval -53.0 to 514.8	-18.00 mL/kg BW Interval -119.0 to 79.0
Ventilatory Parameter: Tidal Volume -- Change From Baseline in Tidal Volume (mL/kg BW) at All Timepoints up to Day 3 (72 Hours) and at Day 28 36 hours	54.50 mL/kg BW Interval -219.0 to 532.4	13.40 mL/kg BW Interval -67.0 to 146.0
Ventilatory Parameter: Tidal Volume -- Change From Baseline in Tidal Volume (mL/kg BW) at All Timepoints up to Day 3 (72 Hours) and at Day 28 48 hours	-34.00 mL/kg BW Interval -125.0 to 512.0	-17.00 mL/kg BW Interval -160.0 to 230.0
Ventilatory Parameter: Tidal Volume -- Change From Baseline in Tidal Volume (mL/kg BW) at All Timepoints up to Day 3 (72 Hours) and at Day 28 54 hours	7.00 mL/kg BW Interval -250.0 to 521.0	30.00 mL/kg BW Interval -116.0 to 320.0
Ventilatory Parameter: Tidal Volume -- Change From Baseline in Tidal Volume (mL/kg BW) at All Timepoints up to Day 3 (72 Hours) and at Day 28 60 hours	-8.00 mL/kg BW Interval -129.0 to 233.0	17.00 mL/kg BW Interval -141.0 to 256.0
Ventilatory Parameter: Tidal Volume -- Change From Baseline in Tidal Volume (mL/kg BW) at All Timepoints up to Day 3 (72 Hours) and at Day 28 72 hours	73.50 mL/kg BW Interval -272.0 to 271.6	11.50 mL/kg BW Interval -136.0 to 234.0
Ventilatory Parameter: Tidal Volume -- Change From Baseline in Tidal Volume (mL/kg BW) at All Timepoints up to Day 3 (72 Hours) and at Day 28 28 day	5.00 mL/kg BW Interval -257.0 to 35.8	-90.50 mL/kg BW Interval -325.0 to -26.0

SECONDARY outcome

Timeframe: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28

Ventilatory parameter: Change from baseline in respiratory rate (breaths/minute) at all timepoints up to Day 3 (72 hours) and at Day 28. The change was calculated from two time points as the value at the later time point minus the value at baseline. Respiratory rate is the number of breaths taken per minute.

Outcome measures

Outcome measures
Measure	Control Cohort n=8 Participants Patients receiving standard-of-care (SoC)	Poractant Alfa Treated Cohort n=13 Participants Patients treated with CUROSURF® (poractant alfa), as an add-on to standard-of-care (SoC)
Ventilatory Parameter: Respiratory Rate -- Change From Baseline in Respiratory Rate (Breaths/Minute) at All Timepoints up to Day 3 (72 Hours) and at Day 28 6 hours	0.0 breaths/minute Interval -4.0 to 5.0	0.0 breaths/minute Interval -2.0 to 1.0
Ventilatory Parameter: Respiratory Rate -- Change From Baseline in Respiratory Rate (Breaths/Minute) at All Timepoints up to Day 3 (72 Hours) and at Day 28 12 hours	0.0 breaths/minute Interval -1.0 to 5.0	0.0 breaths/minute Interval -2.0 to 8.0
Ventilatory Parameter: Respiratory Rate -- Change From Baseline in Respiratory Rate (Breaths/Minute) at All Timepoints up to Day 3 (72 Hours) and at Day 28 24 hours	2.50 breaths/minute Interval -1.0 to 8.0	0.0 breaths/minute Interval -2.0 to 6.0
Ventilatory Parameter: Respiratory Rate -- Change From Baseline in Respiratory Rate (Breaths/Minute) at All Timepoints up to Day 3 (72 Hours) and at Day 28 30 hours	4.0 breaths/minute Interval -9.0 to 17.0	0.0 breaths/minute Interval -3.0 to 4.0
Ventilatory Parameter: Respiratory Rate -- Change From Baseline in Respiratory Rate (Breaths/Minute) at All Timepoints up to Day 3 (72 Hours) and at Day 28 36 hours	1.0 breaths/minute Interval -11.0 to 11.0	0.0 breaths/minute Interval -4.0 to 4.0
Ventilatory Parameter: Respiratory Rate -- Change From Baseline in Respiratory Rate (Breaths/Minute) at All Timepoints up to Day 3 (72 Hours) and at Day 28 48 hours	1.50 breaths/minute Interval -11.0 to 11.0	0.0 breaths/minute Interval -6.0 to 4.0
Ventilatory Parameter: Respiratory Rate -- Change From Baseline in Respiratory Rate (Breaths/Minute) at All Timepoints up to Day 3 (72 Hours) and at Day 28 54 hours	0.00 breaths/minute Interval -8.0 to 14.0	0.0 breaths/minute Interval -15.0 to 8.0
Ventilatory Parameter: Respiratory Rate -- Change From Baseline in Respiratory Rate (Breaths/Minute) at All Timepoints up to Day 3 (72 Hours) and at Day 28 60 hours	0.0 breaths/minute Interval -10.0 to 13.0	0.0 breaths/minute Interval -15.0 to 15.0
Ventilatory Parameter: Respiratory Rate -- Change From Baseline in Respiratory Rate (Breaths/Minute) at All Timepoints up to Day 3 (72 Hours) and at Day 28 72 hours	1.0 breaths/minute Interval -6.0 to 13.0	0.00 breaths/minute Interval -14.0 to 13.0
Ventilatory Parameter: Respiratory Rate -- Change From Baseline in Respiratory Rate (Breaths/Minute) at All Timepoints up to Day 3 (72 Hours) and at Day 28 28 day	10.0 breaths/minute Interval -6.0 to 12.0	14.0 breaths/minute Interval 2.0 to 26.0

SECONDARY outcome

Timeframe: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28

Ventilatory parameter: Change from baseline in dynamic compliance (mL/cmH2O) at all timepoints up to Day 3 (72 hours) and at Day 28. The change was calculated from two time points as the value at the later time point minus the value at baseline. Dynamic compliance: is the continuous measurement of pulmonary compliance calculated at each point representing schematic changes during rhythmic breathing. Dynamic compliance monitors both elastic and airway resistance.

Outcome measures

Outcome measures
Measure	Control Cohort n=8 Participants Patients receiving standard-of-care (SoC)	Poractant Alfa Treated Cohort n=13 Participants Patients treated with CUROSURF® (poractant alfa), as an add-on to standard-of-care (SoC)
Ventilatory Parameter: Dynamic Compliance -- Change From Baseline in Dynamic Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 60 hours	0.85 mL/cmH2O Interval -5.5 to 7.0	-0.05 mL/cmH2O Interval -3.9 to 5.2
Ventilatory Parameter: Dynamic Compliance -- Change From Baseline in Dynamic Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 6 hours	-1.0 mL/cmH2O Interval -4.0 to 9.2	0.70 mL/cmH2O Interval -6.3 to 13.3
Ventilatory Parameter: Dynamic Compliance -- Change From Baseline in Dynamic Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 12 hours	0.50 mL/cmH2O Interval -4.0 to 15.5	-0.70 mL/cmH2O Interval -4.0 to 3.5
Ventilatory Parameter: Dynamic Compliance -- Change From Baseline in Dynamic Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 24 hours	1.20 mL/cmH2O Interval -11.7 to 6.3	-0.55 mL/cmH2O Interval -5.3 to 2.9
Ventilatory Parameter: Dynamic Compliance -- Change From Baseline in Dynamic Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 30 hours	7.50 mL/cmH2O Interval -1.0 to 46.0	1.30 mL/cmH2O Interval -0.6 to 188.8
Ventilatory Parameter: Dynamic Compliance -- Change From Baseline in Dynamic Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 36 hours	3.00 mL/cmH2O Interval -1.9 to 63.0	2.25 mL/cmH2O Interval -0.4 to 6.2
Ventilatory Parameter: Dynamic Compliance -- Change From Baseline in Dynamic Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 48 hours	2.00 mL/cmH2O Interval -10.5 to 103.0	0.52 mL/cmH2O Interval -12.8 to 14.2
Ventilatory Parameter: Dynamic Compliance -- Change From Baseline in Dynamic Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 54 hours	1.80 mL/cmH2O Interval -23.9 to 105.0	0.98 mL/cmH2O Interval -4.1 to 11.3
Ventilatory Parameter: Dynamic Compliance -- Change From Baseline in Dynamic Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 72 hours	-1.25 mL/cmH2O Interval -25.7 to 7.0	0.0 mL/cmH2O Interval -10.5 to 14.5
Ventilatory Parameter: Dynamic Compliance -- Change From Baseline in Dynamic Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 28 day	-5.25 mL/cmH2O Interval -24.5 to 14.0	-3.10 mL/cmH2O Interval -13.0 to 0.7

SECONDARY outcome

Timeframe: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28

Ventilatory parameter: static compliance -- change from baseline in static compliance (mL/cmH2O) at all timepoints up to Day 3 (72 hours) and at Day 28. The change was calculated from two time points as the value at the later time point minus the value at baseline. At each time point the number of patients that contributed with a result value is indicated for both study arms. Static Compliance: represents pulmonary compliance at a given fixed volume when there is no airflow, and muscles are relaxed.

Outcome measures

Outcome measures
Measure	Control Cohort n=8 Participants Patients receiving standard-of-care (SoC)	Poractant Alfa Treated Cohort n=13 Participants Patients treated with CUROSURF® (poractant alfa), as an add-on to standard-of-care (SoC)
Ventilatory Parameter: Static Compliance -- Change From Baseline in Static Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 30 hours	7.00 mL/cmH2O Interval -1.0 to 8.0	1.30 mL/cmH2O Interval 0.2 to 12.8
Ventilatory Parameter: Static Compliance -- Change From Baseline in Static Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 36 hours	2.50 mL/cmH2O Interval -1.9 to 7.5	2.10 mL/cmH2O Interval -0.4 to 6.2
Ventilatory Parameter: Static Compliance -- Change From Baseline in Static Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 6 hours	-2.00 mL/cmH2O Interval -4.0 to 9.2	0.40 mL/cmH2O Interval -4.0 to 12.2
Ventilatory Parameter: Static Compliance -- Change From Baseline in Static Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 12 hours	0.15 mL/cmH2O Interval -4.0 to 8.5	-0.81 mL/cmH2O Interval -3.5 to 4.3
Ventilatory Parameter: Static Compliance -- Change From Baseline in Static Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 24 hours	1.54 mL/cmH2O Interval 0.0 to 6.3	-0.40 mL/cmH2O Interval -3.6 to 5.1
Ventilatory Parameter: Static Compliance -- Change From Baseline in Static Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 48 hours	-3.50 mL/cmH2O Interval -10.5 to 7.4	-0.40 mL/cmH2O Interval -5.7 to 9.2
Ventilatory Parameter: Static Compliance -- Change From Baseline in Static Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 54 hours	1.80 mL/cmH2O Interval -23.9 to 7.1	-0.26 mL/cmH2O Interval -3.7 to 6.4
Ventilatory Parameter: Static Compliance -- Change From Baseline in Static Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 60 hours	0.85 mL/cmH2O Interval -5.5 to 7.0	-0.40 mL/cmH2O Interval -3.2 to 5.6
Ventilatory Parameter: Static Compliance -- Change From Baseline in Static Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 72 hours	3.00 mL/cmH2O Interval -25.7 to 7.0	0.30 mL/cmH2O Interval -1.3 to 13.2
Ventilatory Parameter: Static Compliance -- Change From Baseline in Static Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 28 day	-24.50 mL/cmH2O Interval -24.5 to -24.5	-2.70 mL/cmH2O Interval -13.0 to 0.7

SECONDARY outcome

Timeframe: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28

Ventilatory parameter: Positive End-Expiratory Pressure -- Change from baseline in PEEP (cmH2O) at all timepoints up to Day 3 (72 hours) and at Day 28. The change was calculated from two time points as the value at the later time point minus the value at baseline. At each time point the number of patients that contributed with a result value is indicated for both study arms. Positive end-expiratory pressure (PEEP) is the positive pressure that will remain in the airways at the end of the respiratory cycle (end of exhalation) that is greater than the atmospheric pressure in mechanically ventilated patients.

Outcome measures

Outcome measures
Measure	Control Cohort n=8 Participants Patients receiving standard-of-care (SoC)	Poractant Alfa Treated Cohort n=13 Participants Patients treated with CUROSURF® (poractant alfa), as an add-on to standard-of-care (SoC)
Ventilatory Parameter: Positive End-Expiratory Pressure (PEEP) -- Change From Baseline in PEEP (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 72 hours	-1.00 cmH2O Interval -10.0 to 3.0	0.00 cmH2O Interval -2.0 to 1.0
Ventilatory Parameter: Positive End-Expiratory Pressure (PEEP) -- Change From Baseline in PEEP (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 6 hours	0.00 cmH2O Interval -0.3 to 2.0	0.00 cmH2O Interval -4.0 to 0.1
Ventilatory Parameter: Positive End-Expiratory Pressure (PEEP) -- Change From Baseline in PEEP (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 12 hours	0.50 cmH2O Interval 0.0 to 2.0	0.00 cmH2O Interval -2.0 to 0.3
Ventilatory Parameter: Positive End-Expiratory Pressure (PEEP) -- Change From Baseline in PEEP (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 24 hours	2.00 cmH2O Interval -3.0 to 2.0	0.00 cmH2O Interval -4.0 to 7.0
Ventilatory Parameter: Positive End-Expiratory Pressure (PEEP) -- Change From Baseline in PEEP (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 30 hours	0.00 cmH2O Interval -4.0 to 2.0	0.00 cmH2O Interval -4.0 to 1.0
Ventilatory Parameter: Positive End-Expiratory Pressure (PEEP) -- Change From Baseline in PEEP (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 36 hours	0.00 cmH2O Interval -5.0 to 5.0	0.00 cmH2O Interval -4.0 to 1.0
Ventilatory Parameter: Positive End-Expiratory Pressure (PEEP) -- Change From Baseline in PEEP (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 48 hours	0.00 cmH2O Interval -8.0 to 3.0	0.00 cmH2O Interval -4.0 to 1.0
Ventilatory Parameter: Positive End-Expiratory Pressure (PEEP) -- Change From Baseline in PEEP (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 54 hours	-0.50 cmH2O Interval -10.0 to 3.0	-0.50 cmH2O Interval -7.6 to 1.0
Ventilatory Parameter: Positive End-Expiratory Pressure (PEEP) -- Change From Baseline in PEEP (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 60 hours	-0.45 cmH2O Interval -10.0 to 3.0	-0.50 cmH2O Interval -6.0 to 1.0
Ventilatory Parameter: Positive End-Expiratory Pressure (PEEP) -- Change From Baseline in PEEP (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 28 day	-3.20 cmH2O Interval -11.8 to -1.0	-2.00 cmH2O Interval -4.0 to 0.2

SECONDARY outcome

Timeframe: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28

Ventilatory parameter: Peak Inspiratory Pressure -- Change from baseline in peak inspiratory pressure (cmH2O) at all timepoints up to Day 3 (72 hours) and at Day 28. The change was calculated from two time points as the value at the later time point minus the value at baseline. At each time point the number of patients that contributed with a result value is indicated for both study arms. Peak inspiratory pressure (PIP) is the highest level of pressure applied to the lungs during inhalation. In mechanical ventilation the number reflects a positive pressure in centimetres of water pressure (cmH2O).

Outcome measures

Outcome measures
Measure	Control Cohort n=8 Participants Patients receiving standard-of-care (SoC)	Poractant Alfa Treated Cohort n=13 Participants Patients treated with CUROSURF® (poractant alfa), as an add-on to standard-of-care (SoC)
Ventilatory Parameter: Peak Inspiratory Pressure -- Change From Baseline in Peak Inspiratory Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 6 hours	0.00 cmH2O Interval -18.0 to 5.0	0.00 cmH2O Interval -8.0 to 4.0
Ventilatory Parameter: Peak Inspiratory Pressure -- Change From Baseline in Peak Inspiratory Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 12 hours	2.00 cmH2O Interval -0.1 to 5.0	0.00 cmH2O Interval -8.0 to 3.4
Ventilatory Parameter: Peak Inspiratory Pressure -- Change From Baseline in Peak Inspiratory Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 24 hours	3.00 cmH2O Interval -4.1 to 6.0	-0.50 cmH2O Interval -8.0 to 2.2
Ventilatory Parameter: Peak Inspiratory Pressure -- Change From Baseline in Peak Inspiratory Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 30 hours	1.00 cmH2O Interval -4.7 to 6.0	-2.00 cmH2O Interval -6.0 to 5.0
Ventilatory Parameter: Peak Inspiratory Pressure -- Change From Baseline in Peak Inspiratory Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 36 hours	3.00 cmH2O Interval -4.7 to 6.0	-1.00 cmH2O Interval -8.0 to 2.1
Ventilatory Parameter: Peak Inspiratory Pressure -- Change From Baseline in Peak Inspiratory Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 48 hours	0.00 cmH2O Interval -5.4 to 10.0	-2.00 cmH2O Interval -8.0 to 8.0
Ventilatory Parameter: Peak Inspiratory Pressure -- Change From Baseline in Peak Inspiratory Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 54 hours	2.00 cmH2O Interval -5.5 to 8.0	-3.00 cmH2O Interval -8.0 to 1.0
Ventilatory Parameter: Peak Inspiratory Pressure -- Change From Baseline in Peak Inspiratory Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 60 hours	0.00 cmH2O Interval -6.1 to 7.0	-3.00 cmH2O Interval -7.0 to 2.0
Ventilatory Parameter: Peak Inspiratory Pressure -- Change From Baseline in Peak Inspiratory Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 72 hours	4.50 cmH2O Interval -7.0 to 12.0	-3.00 cmH2O Interval -13.0 to 4.0
Ventilatory Parameter: Peak Inspiratory Pressure -- Change From Baseline in Peak Inspiratory Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 28 day	4.00 cmH2O Interval -3.5 to 5.0	-4.00 cmH2O Interval -16.0 to 8.0

SECONDARY outcome

Timeframe: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28

Ventilatory parameter: Plateau Pressure -- Change from baseline in plateau pressure (cmH2O) at all timepoints up to Day 3 (72 hours) and at Day 28. The change was calculated from two time points as the value at the later time point minus the value at baseline. At each time point the number of patients that contributed with a result value is indicated for both study arms. Plateau pressure is the pressure that is applied by the mechanical ventilator to the small airways and alveoli.

Outcome measures

Outcome measures
Measure	Control Cohort n=8 Participants Patients receiving standard-of-care (SoC)	Poractant Alfa Treated Cohort n=13 Participants Patients treated with CUROSURF® (poractant alfa), as an add-on to standard-of-care (SoC)
Ventilatory Parameter: Plateau Pressure -- Change From Baseline in Plateau Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 6 hours	1.25 cmH2O Interval 0.0 to 3.0	-1.00 cmH2O Interval -8.0 to 2.0
Ventilatory Parameter: Plateau Pressure -- Change From Baseline in Plateau Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 12 hours	2.00 cmH2O Interval 0.0 to 3.0	-1.50 cmH2O Interval -8.0 to 2.0
Ventilatory Parameter: Plateau Pressure -- Change From Baseline in Plateau Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 24 hours	0.50 cmH2O Interval -5.0 to 6.0	-1.50 cmH2O Interval -8.0 to 2.0
Ventilatory Parameter: Plateau Pressure -- Change From Baseline in Plateau Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 30 hours	0.00 cmH2O Interval -1.0 to 6.0	-3.00 cmH2O Interval -7.0 to 1.0
Ventilatory Parameter: Plateau Pressure -- Change From Baseline in Plateau Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 36 hours	1.00 cmH2O Interval -2.0 to 4.0	-2.00 cmH2O Interval -8.0 to 1.0
Ventilatory Parameter: Plateau Pressure -- Change From Baseline in Plateau Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 48 hours	3.00 cmH2O Interval -4.0 to 10.0	-3.00 cmH2O Interval -8.0 to 1.0
Ventilatory Parameter: Plateau Pressure -- Change From Baseline in Plateau Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 54 hours	1.50 cmH2O Interval -4.0 to 10.0	-3.50 cmH2O Interval -8.0 to 1.0
Ventilatory Parameter: Plateau Pressure -- Change From Baseline in Plateau Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 60 hours	0.50 cmH2O Interval -5.0 to 7.0	-2.50 cmH2O Interval -7.0 to 2.0
Ventilatory Parameter: Plateau Pressure -- Change From Baseline in Plateau Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 72 hours	1.50 cmH2O Interval -8.0 to 11.0	-3.00 cmH2O Interval -8.0 to 3.0
Ventilatory Parameter: Plateau Pressure -- Change From Baseline in Plateau Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 28 day	2.00 cmH2O Interval -2.0 to 6.0	-4.00 cmH2O Interval -16.0 to 15.7

SECONDARY outcome

Timeframe: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28

Change from baseline in blood gas analysis acid-base balance parameters -- pH. The change was calculated from two time points as the value at the later time point minus the value at baseline. Arterial blood gas was measured at 6, 12, 24, 30, 36, 48, 54, 60 and 72 hours after randomisation and up to Day 28 or till the patient was discharged from the ICU - whichever occurred earlier.

Outcome measures

Outcome measures
Measure	Control Cohort n=8 Participants Patients receiving standard-of-care (SoC)	Poractant Alfa Treated Cohort n=13 Participants Patients treated with CUROSURF® (poractant alfa), as an add-on to standard-of-care (SoC)
Blood Gas Analysis Acid-base Balance Parameters: Change From Baseline in Blood Gas Analysis Acid-base Balance Parameters -- pH 6 hours	0.0000 pH Interval -0.02 to 0.1	0.0080 pH Interval -0.24 to 0.127
Blood Gas Analysis Acid-base Balance Parameters: Change From Baseline in Blood Gas Analysis Acid-base Balance Parameters -- pH 12 hours	0.0050 pH Interval -0.08 to 0.08	0.0100 pH Interval -0.15 to 0.149
Blood Gas Analysis Acid-base Balance Parameters: Change From Baseline in Blood Gas Analysis Acid-base Balance Parameters -- pH 24 hours	0.0315 pH Interval -0.11 to 0.15	0.0160 pH Interval -0.15 to 0.11
Blood Gas Analysis Acid-base Balance Parameters: Change From Baseline in Blood Gas Analysis Acid-base Balance Parameters -- pH 30 hours	0.0300 pH Interval -0.09 to 0.15	0.0100 pH Interval -0.12 to 0.21
Blood Gas Analysis Acid-base Balance Parameters: Change From Baseline in Blood Gas Analysis Acid-base Balance Parameters -- pH 36 hours	0.0050 pH Interval -0.11 to 0.18	0.0260 pH Interval -0.08 to 0.17
Blood Gas Analysis Acid-base Balance Parameters: Change From Baseline in Blood Gas Analysis Acid-base Balance Parameters -- pH 48 hours	0.0050 pH Interval -0.1 to 0.16	0.0300 pH Interval -0.32 to 0.17
Blood Gas Analysis Acid-base Balance Parameters: Change From Baseline in Blood Gas Analysis Acid-base Balance Parameters -- pH 54 hours	0.0500 pH Interval -0.15 to 0.457	0.0185 pH Interval -0.23 to 0.17
Blood Gas Analysis Acid-base Balance Parameters: Change From Baseline in Blood Gas Analysis Acid-base Balance Parameters -- pH 60 hours	-0.0500 pH Interval -0.14 to 0.348	0.0000 pH Interval -0.369 to 0.14
Blood Gas Analysis Acid-base Balance Parameters: Change From Baseline in Blood Gas Analysis Acid-base Balance Parameters -- pH 72 hours	0.0400 pH Interval -0.17 to 0.27	0.0120 pH Interval -0.369 to 0.18
Blood Gas Analysis Acid-base Balance Parameters: Change From Baseline in Blood Gas Analysis Acid-base Balance Parameters -- pH 28 day	-0.0400 pH Interval -0.05 to -0.021	0.0500 pH Interval -0.01 to 0.23
Blood Gas Analysis Acid-base Balance Parameters: Change From Baseline in Blood Gas Analysis Acid-base Balance Parameters -- pH ICU Discharge	—	0.0450 pH Interval 0.045 to 0.045

SECONDARY outcome

Timeframe: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28

Change from baseline in blood gas analysis acid-base balance parameter -- pCO2. The change was calculated from two time points as the value at the later time point minus the value at baseline. Arterial blood gas was measured at 6, 12, 24, 30, 36, 48, 54, 60 and 72 hours after randomisation and up to Day 28 or till the patient was discharged from the ICU - whichever occurred earlier.

Outcome measures

Outcome measures
Measure	Control Cohort n=8 Participants Patients receiving standard-of-care (SoC)	Poractant Alfa Treated Cohort n=13 Participants Patients treated with CUROSURF® (poractant alfa), as an add-on to standard-of-care (SoC)
Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Carbon Dioxide (pCO2) 6 hours	-2.210 mmHg Interval -10.4 to 5.0	1.535 mmHg Interval -14.25 to 49.0
Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Carbon Dioxide (pCO2) 12 hours	-0.150 mmHg Interval -11.0 to 11.0	1.730 mmHg Interval -21.76 to 22.1
Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Carbon Dioxide (pCO2) 24 hours	-2.610 mmHg Interval -19.0 to 18.0	-2.000 mmHg Interval -29.26 to 18.1
Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Carbon Dioxide (pCO2) 30 hours	-5.700 mmHg Interval -11.4 to 10.6	1.880 mmHg Interval -21.5 to 20.25
Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Carbon Dioxide (pCO2) 36 hours	-3.350 mmHg Interval -15.0 to 23.0	1.720 mmHg Interval -13.5 to 12.0
Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Carbon Dioxide (pCO2) 48 hours	2.500 mmHg Interval -11.0 to 10.2	0.300 mmHg Interval -14.5 to 16.0
Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Carbon Dioxide (pCO2) 54 hours	-0.600 mmHg Interval -38.5 to 13.6	-1.500 mmHg Interval -13.0 to 30.0
Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Carbon Dioxide (pCO2) 60 hours	3.400 mmHg Interval -5.4 to 28.0	-0.230 mmHg Interval -10.0 to 19.0
Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Carbon Dioxide (pCO2) 72 hours	0.000 mmHg Interval -10.87 to 33.0	0.750 mmHg Interval -18.0 to 33.1
Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Carbon Dioxide (pCO2) 28 day	6.150 mmHg Interval -8.0 to 52.0	12.000 mmHg Interval -13.4 to 30.01
Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Carbon Dioxide (pCO2) ICU Discharge	—	-9.600 mmHg Interval -9.6 to -9.6

SECONDARY outcome

Timeframe: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28

Change from baseline in blood gas analysis acid-base balance parameter -- pO2. The change was calculated from two time points as the value at the later time point minus the value at baseline. Arterial blood gas was measured at 6, 12, 24, 30, 36, 48, 54, 60 and 72 hours after randomisation and up to Day 28 or till the patient was discharged from the ICU - whichever occurred earlier.

Outcome measures

Outcome measures
Measure	Control Cohort n=8 Participants Patients receiving standard-of-care (SoC)	Poractant Alfa Treated Cohort n=13 Participants Patients treated with CUROSURF® (poractant alfa), as an add-on to standard-of-care (SoC)
Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Oxygen (pO2) 6 hours	0.500 mmHg Interval -9.0 to 210.01	6.550 mmHg Interval -14.6 to 165.61
Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Oxygen (pO2) 12 hours	12.500 mmHg Interval -8.85 to 158.7	1.000 mmHg Interval -20.78 to 50.85
Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Oxygen (pO2) 24 hours	7.000 mmHg Interval -6.3 to 82.7	1.100 mmHg Interval -19.28 to 98.26
Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Oxygen (pO2) 30 hours	3.000 mmHg Interval -11.4 to 181.1	2.000 mmHg Interval -25.28 to 29.1
Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Oxygen (pO2) 36 hours	7.000 mmHg Interval -13.3 to 171.1	2.600 mmHg Interval -16.35 to 28.35
Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Oxygen (pO2) 48 hours	6.250 mmHg Interval -10.3 to 63.1	0.000 mmHg Interval -19.2 to 52.0
Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Oxygen (pO2) 54 hours	4.300 mmHg Interval -23.33 to 116.1	2.250 mmHg Interval -29.56 to 43.0
Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Oxygen (pO2) 60 hours	15.000 mmHg Interval -13.05 to 156.1	0.000 mmHg Interval -32.26 to 21.0
Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Oxygen (pO2) 72 hours	6.000 mmHg Interval -6.3 to 103.1	5.100 mmHg Interval -7.0 to 50.25
Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Oxygen (pO2) 28 day	8.100 mmHg Interval -7.0 to 33.0	-7.700 mmHg Interval -26.78 to 34.5
Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Oxygen (pO2) ICU Discharge	—	-10.730 mmHg Interval -10.73 to -10.73

SECONDARY outcome

Timeframe: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28

Change from baseline in blood gas analysis acid-base balance parameter -- Bicarbonate (HCO3). The change was calculated from two time points as the value at the later time point minus the value at baseline. Measured at 6-12-24h after each poractant alfa administration up to 72 hours and at similar timepoints in the control group (6, 12, 24, 30, 36, 48, 54, 60 and 72 hours after randomisation) and then every 24 hours till the patient is discharged from the ICU

Outcome measures

Outcome measures
Measure	Control Cohort n=8 Participants Patients receiving standard-of-care (SoC)	Poractant Alfa Treated Cohort n=13 Participants Patients treated with CUROSURF® (poractant alfa), as an add-on to standard-of-care (SoC)
Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Bicarbonate (HCO3) 6 hours	1.05 mmol/L Interval -1.1 to 19.3	0.70 mmol/L Interval -3.8 to 4.4
Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Bicarbonate (HCO3) 12 hours	1.10 mmol/L Interval -0.6 to 5.0	1.30 mmol/L Interval -2.4 to 5.6
Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Bicarbonate (HCO3) 24 hours	1.65 mmol/L Interval -3.5 to 6.7	1.80 mmol/L Interval -2.4 to 5.5
Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Bicarbonate (HCO3) 30 hours	2.30 mmol/L Interval -3.0 to 5.7	2.30 mmol/L Interval -2.4 to 6.3
Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Bicarbonate (HCO3) 36 hours	1.75 mmol/L Interval -2.8 to 7.5	2.70 mmol/L Interval -2.7 to 6.9
Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Bicarbonate (HCO3) 48 hours	1.60 mmol/L Interval -4.1 to 7.8	3.50 mmol/L Interval -13.4 to 7.7
Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Bicarbonate (HCO3) 54 hours	0.80 mmol/L Interval -19.1 to 8.9	2.10 mmol/L Interval -11.4 to 5.8
Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Bicarbonate (HCO3) 60 hours	3.30 mmol/L Interval -3.9 to 10.7	2.80 mmol/L Interval -2.9 to 9.1
Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Bicarbonate (HCO3) 72 hours	3.00 mmol/L Interval -4.5 to 10.4	4.00 mmol/L Interval 0.6 to 11.6
Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Bicarbonate (HCO3) 28 day	1.90 mmol/L Interval -6.4 to 33.0	13.20 mmol/L Interval 5.3 to 17.5
Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Bicarbonate (HCO3) ICU Discharge	—	-3.90 mmol/L Interval -3.9 to -3.9

SECONDARY outcome

Timeframe: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28

Change from baseline in blood parameter -- Lactate The change was calculated from two time points as the value at the later time point minus the value at baseline. At each time point the number of patients that contributed with a result value is indicated for both study arms. Arterial blood lactate was measured at 6, 12, 24, 30, 36, 48, 54, 60, and 72 hours after randomisation and up to Day 28 or till the patient was discharged from the ICU - whichever occurred earlier.

Outcome measures

Outcome measures
Measure	Control Cohort n=8 Participants Patients receiving standard-of-care (SoC)	Poractant Alfa Treated Cohort n=13 Participants Patients treated with CUROSURF® (poractant alfa), as an add-on to standard-of-care (SoC)
Change From Baseline in Blood Parameter -- Lactate 6 hours	0.05 mmol/L Interval -0.5 to 1.1	-0.05 mmol/L Interval -1.0 to 0.5
Change From Baseline in Blood Parameter -- Lactate 12 hours	0.55 mmol/L Interval -0.8 to 1.8	0.20 mmol/L Interval -1.1 to 0.6
Change From Baseline in Blood Parameter -- Lactate 24 hours	-0.10 mmol/L Interval -0.4 to 1.3	-0.10 mmol/L Interval -0.9 to 0.5
Change From Baseline in Blood Parameter -- Lactate 30 hours	0.30 mmol/L Interval -0.4 to 1.2	0.00 mmol/L Interval -0.8 to 1.0
Change From Baseline in Blood Parameter -- Lactate 36 hours	0.55 mmol/L Interval -0.8 to 1.5	-0.10 mmol/L Interval -0.9 to 9.8
Change From Baseline in Blood Parameter -- Lactate 48 hours	-0.10 mmol/L Interval -0.7 to 1.5	-0.10 mmol/L Interval -1.2 to 17.6
Change From Baseline in Blood Parameter -- Lactate 54 hours	0.25 mmol/L Interval -0.3 to 1.3	0.00 mmol/L Interval -1.5 to 21.6
Change From Baseline in Blood Parameter -- Lactate 60 hours	0.10 mmol/L Interval -1.0 to 1.4	-0.10 mmol/L Interval -1.8 to 19.6
Change From Baseline in Blood Parameter -- Lactate 72 hours	-0.20 mmol/L Interval -1.3 to 0.9	-0.10 mmol/L Interval -1.1 to 1.0
Change From Baseline in Blood Parameter -- Lactate 28 day	-0.60 mmol/L Interval -1.0 to 1.4	-0.10 mmol/L Interval -1.2 to 0.4
Change From Baseline in Blood Parameter -- Lactate ICU Discharge	—	-2.30 mmol/L Interval -2.3 to -2.3

SECONDARY outcome

Timeframe: up to day 28

Population: Safety Population: all randomised patients (who received at least one dose of the study treatment if poractant alfa-treated).

The incidence of treatment-emergent adverse event (TEAEs) leading to death is presented by treatment group.

Outcome measures

Outcome measures
Measure	Control Cohort n=8 Participants Patients receiving standard-of-care (SoC)	Poractant Alfa Treated Cohort n=13 Participants Patients treated with CUROSURF® (poractant alfa), as an add-on to standard-of-care (SoC)
Mortality -- TEAEs Leading to Death	2 Participants	3 Participants

Adverse Events

Control Cohort

Serious events: 3 serious events

Other events: 5 other events

Deaths: 2 deaths

Poractant Alfa Treated Cohort

Serious events: 5 serious events

Other events: 11 other events

Deaths: 4 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical Trial Transparency

Chiesi Farmaceutici S.p.A.

Phone: + 39 0521 2791

Email: [email protected]

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

Measure	Control Cohort n=8 participants at risk Patients receiving standard-of-care (SoC)	Poractant Alfa Treated Cohort n=13 participants at risk Patients treated with CUROSURF® (poractant alfa), as an add-on to standard-of-care (SoC)
Cardiac disorders Atrioventricular block	0.00% 0/8 • From screening procedures (Day 0) to the end of the study (Day 28). Analysis of adverse events (AEs) was performed on TEAEs, defined as AEs that started at or after treatment start (for the poractant alfa group) or at or after randomisation (for the control group). Safety set (SAF) was used to evaluate AEs and serious AEs (SAEs). The SAF included all enrolled patients, except for one, who was randomised to receive poractant alfa was not treated. All patients included in the SAF were also included in the ITT.	7.7% 1/13 • Number of events 1 • From screening procedures (Day 0) to the end of the study (Day 28). Analysis of adverse events (AEs) was performed on TEAEs, defined as AEs that started at or after treatment start (for the poractant alfa group) or at or after randomisation (for the control group). Safety set (SAF) was used to evaluate AEs and serious AEs (SAEs). The SAF included all enrolled patients, except for one, who was randomised to receive poractant alfa was not treated. All patients included in the SAF were also included in the ITT.
Cardiac disorders Cardiogenic shock	0.00% 0/8 • From screening procedures (Day 0) to the end of the study (Day 28). Analysis of adverse events (AEs) was performed on TEAEs, defined as AEs that started at or after treatment start (for the poractant alfa group) or at or after randomisation (for the control group). Safety set (SAF) was used to evaluate AEs and serious AEs (SAEs). The SAF included all enrolled patients, except for one, who was randomised to receive poractant alfa was not treated. All patients included in the SAF were also included in the ITT.	7.7% 1/13 • Number of events 1 • From screening procedures (Day 0) to the end of the study (Day 28). Analysis of adverse events (AEs) was performed on TEAEs, defined as AEs that started at or after treatment start (for the poractant alfa group) or at or after randomisation (for the control group). Safety set (SAF) was used to evaluate AEs and serious AEs (SAEs). The SAF included all enrolled patients, except for one, who was randomised to receive poractant alfa was not treated. All patients included in the SAF were also included in the ITT.
Cardiac disorders Myocardial infarction	0.00% 0/8 • From screening procedures (Day 0) to the end of the study (Day 28). Analysis of adverse events (AEs) was performed on TEAEs, defined as AEs that started at or after treatment start (for the poractant alfa group) or at or after randomisation (for the control group). Safety set (SAF) was used to evaluate AEs and serious AEs (SAEs). The SAF included all enrolled patients, except for one, who was randomised to receive poractant alfa was not treated. All patients included in the SAF were also included in the ITT.	7.7% 1/13 • Number of events 1 • From screening procedures (Day 0) to the end of the study (Day 28). Analysis of adverse events (AEs) was performed on TEAEs, defined as AEs that started at or after treatment start (for the poractant alfa group) or at or after randomisation (for the control group). Safety set (SAF) was used to evaluate AEs and serious AEs (SAEs). The SAF included all enrolled patients, except for one, who was randomised to receive poractant alfa was not treated. All patients included in the SAF were also included in the ITT.
Cardiac disorders Right ventricular failure	12.5% 1/8 • Number of events 1 • From screening procedures (Day 0) to the end of the study (Day 28). Analysis of adverse events (AEs) was performed on TEAEs, defined as AEs that started at or after treatment start (for the poractant alfa group) or at or after randomisation (for the control group). Safety set (SAF) was used to evaluate AEs and serious AEs (SAEs). The SAF included all enrolled patients, except for one, who was randomised to receive poractant alfa was not treated. All patients included in the SAF were also included in the ITT.	7.7% 1/13 • Number of events 1 • From screening procedures (Day 0) to the end of the study (Day 28). Analysis of adverse events (AEs) was performed on TEAEs, defined as AEs that started at or after treatment start (for the poractant alfa group) or at or after randomisation (for the control group). Safety set (SAF) was used to evaluate AEs and serious AEs (SAEs). The SAF included all enrolled patients, except for one, who was randomised to receive poractant alfa was not treated. All patients included in the SAF were also included in the ITT.
Blood and lymphatic system disorders Bicytopenia	12.5% 1/8 • Number of events 1 • From screening procedures (Day 0) to the end of the study (Day 28). Analysis of adverse events (AEs) was performed on TEAEs, defined as AEs that started at or after treatment start (for the poractant alfa group) or at or after randomisation (for the control group). Safety set (SAF) was used to evaluate AEs and serious AEs (SAEs). The SAF included all enrolled patients, except for one, who was randomised to receive poractant alfa was not treated. All patients included in the SAF were also included in the ITT.	0.00% 0/13 • From screening procedures (Day 0) to the end of the study (Day 28). Analysis of adverse events (AEs) was performed on TEAEs, defined as AEs that started at or after treatment start (for the poractant alfa group) or at or after randomisation (for the control group). Safety set (SAF) was used to evaluate AEs and serious AEs (SAEs). The SAF included all enrolled patients, except for one, who was randomised to receive poractant alfa was not treated. All patients included in the SAF were also included in the ITT.
Gastrointestinal disorders Haematochezia	12.5% 1/8 • Number of events 1 • From screening procedures (Day 0) to the end of the study (Day 28). Analysis of adverse events (AEs) was performed on TEAEs, defined as AEs that started at or after treatment start (for the poractant alfa group) or at or after randomisation (for the control group). Safety set (SAF) was used to evaluate AEs and serious AEs (SAEs). The SAF included all enrolled patients, except for one, who was randomised to receive poractant alfa was not treated. All patients included in the SAF were also included in the ITT.	0.00% 0/13 • From screening procedures (Day 0) to the end of the study (Day 28). Analysis of adverse events (AEs) was performed on TEAEs, defined as AEs that started at or after treatment start (for the poractant alfa group) or at or after randomisation (for the control group). Safety set (SAF) was used to evaluate AEs and serious AEs (SAEs). The SAF included all enrolled patients, except for one, who was randomised to receive poractant alfa was not treated. All patients included in the SAF were also included in the ITT.
Gastrointestinal disorders Pneumatosis intestinalis	12.5% 1/8 • Number of events 1 • From screening procedures (Day 0) to the end of the study (Day 28). Analysis of adverse events (AEs) was performed on TEAEs, defined as AEs that started at or after treatment start (for the poractant alfa group) or at or after randomisation (for the control group). Safety set (SAF) was used to evaluate AEs and serious AEs (SAEs). The SAF included all enrolled patients, except for one, who was randomised to receive poractant alfa was not treated. All patients included in the SAF were also included in the ITT.	0.00% 0/13 • From screening procedures (Day 0) to the end of the study (Day 28). Analysis of adverse events (AEs) was performed on TEAEs, defined as AEs that started at or after treatment start (for the poractant alfa group) or at or after randomisation (for the control group). Safety set (SAF) was used to evaluate AEs and serious AEs (SAEs). The SAF included all enrolled patients, except for one, who was randomised to receive poractant alfa was not treated. All patients included in the SAF were also included in the ITT.
General disorders Multiple organ dysfunction syndrome	12.5% 1/8 • Number of events 1 • From screening procedures (Day 0) to the end of the study (Day 28). Analysis of adverse events (AEs) was performed on TEAEs, defined as AEs that started at or after treatment start (for the poractant alfa group) or at or after randomisation (for the control group). Safety set (SAF) was used to evaluate AEs and serious AEs (SAEs). The SAF included all enrolled patients, except for one, who was randomised to receive poractant alfa was not treated. All patients included in the SAF were also included in the ITT.	0.00% 0/13 • From screening procedures (Day 0) to the end of the study (Day 28). Analysis of adverse events (AEs) was performed on TEAEs, defined as AEs that started at or after treatment start (for the poractant alfa group) or at or after randomisation (for the control group). Safety set (SAF) was used to evaluate AEs and serious AEs (SAEs). The SAF included all enrolled patients, except for one, who was randomised to receive poractant alfa was not treated. All patients included in the SAF were also included in the ITT.
Infections and infestations Nosocomial infection	12.5% 1/8 • Number of events 1 • From screening procedures (Day 0) to the end of the study (Day 28). Analysis of adverse events (AEs) was performed on TEAEs, defined as AEs that started at or after treatment start (for the poractant alfa group) or at or after randomisation (for the control group). Safety set (SAF) was used to evaluate AEs and serious AEs (SAEs). The SAF included all enrolled patients, except for one, who was randomised to receive poractant alfa was not treated. All patients included in the SAF were also included in the ITT.	0.00% 0/13 • From screening procedures (Day 0) to the end of the study (Day 28). Analysis of adverse events (AEs) was performed on TEAEs, defined as AEs that started at or after treatment start (for the poractant alfa group) or at or after randomisation (for the control group). Safety set (SAF) was used to evaluate AEs and serious AEs (SAEs). The SAF included all enrolled patients, except for one, who was randomised to receive poractant alfa was not treated. All patients included in the SAF were also included in the ITT.
Infections and infestations Sepsis	12.5% 1/8 • Number of events 1 • From screening procedures (Day 0) to the end of the study (Day 28). Analysis of adverse events (AEs) was performed on TEAEs, defined as AEs that started at or after treatment start (for the poractant alfa group) or at or after randomisation (for the control group). Safety set (SAF) was used to evaluate AEs and serious AEs (SAEs). The SAF included all enrolled patients, except for one, who was randomised to receive poractant alfa was not treated. All patients included in the SAF were also included in the ITT.	0.00% 0/13 • From screening procedures (Day 0) to the end of the study (Day 28). Analysis of adverse events (AEs) was performed on TEAEs, defined as AEs that started at or after treatment start (for the poractant alfa group) or at or after randomisation (for the control group). Safety set (SAF) was used to evaluate AEs and serious AEs (SAEs). The SAF included all enrolled patients, except for one, who was randomised to receive poractant alfa was not treated. All patients included in the SAF were also included in the ITT.
Injury, poisoning and procedural complications Post procedural haemorrhage	0.00% 0/8 • From screening procedures (Day 0) to the end of the study (Day 28). Analysis of adverse events (AEs) was performed on TEAEs, defined as AEs that started at or after treatment start (for the poractant alfa group) or at or after randomisation (for the control group). Safety set (SAF) was used to evaluate AEs and serious AEs (SAEs). The SAF included all enrolled patients, except for one, who was randomised to receive poractant alfa was not treated. All patients included in the SAF were also included in the ITT.	7.7% 1/13 • Number of events 1 • From screening procedures (Day 0) to the end of the study (Day 28). Analysis of adverse events (AEs) was performed on TEAEs, defined as AEs that started at or after treatment start (for the poractant alfa group) or at or after randomisation (for the control group). Safety set (SAF) was used to evaluate AEs and serious AEs (SAEs). The SAF included all enrolled patients, except for one, who was randomised to receive poractant alfa was not treated. All patients included in the SAF were also included in the ITT.
Injury, poisoning and procedural complications Soft tissue injury	0.00% 0/8 • From screening procedures (Day 0) to the end of the study (Day 28). Analysis of adverse events (AEs) was performed on TEAEs, defined as AEs that started at or after treatment start (for the poractant alfa group) or at or after randomisation (for the control group). Safety set (SAF) was used to evaluate AEs and serious AEs (SAEs). The SAF included all enrolled patients, except for one, who was randomised to receive poractant alfa was not treated. All patients included in the SAF were also included in the ITT.	7.7% 1/13 • Number of events 1 • From screening procedures (Day 0) to the end of the study (Day 28). Analysis of adverse events (AEs) was performed on TEAEs, defined as AEs that started at or after treatment start (for the poractant alfa group) or at or after randomisation (for the control group). Safety set (SAF) was used to evaluate AEs and serious AEs (SAEs). The SAF included all enrolled patients, except for one, who was randomised to receive poractant alfa was not treated. All patients included in the SAF were also included in the ITT.
Nervous system disorders Cerebral artery embolism	12.5% 1/8 • Number of events 1 • From screening procedures (Day 0) to the end of the study (Day 28). Analysis of adverse events (AEs) was performed on TEAEs, defined as AEs that started at or after treatment start (for the poractant alfa group) or at or after randomisation (for the control group). Safety set (SAF) was used to evaluate AEs and serious AEs (SAEs). The SAF included all enrolled patients, except for one, who was randomised to receive poractant alfa was not treated. All patients included in the SAF were also included in the ITT.	0.00% 0/13 • From screening procedures (Day 0) to the end of the study (Day 28). Analysis of adverse events (AEs) was performed on TEAEs, defined as AEs that started at or after treatment start (for the poractant alfa group) or at or after randomisation (for the control group). Safety set (SAF) was used to evaluate AEs and serious AEs (SAEs). The SAF included all enrolled patients, except for one, who was randomised to receive poractant alfa was not treated. All patients included in the SAF were also included in the ITT.
Nervous system disorders Cerebral disorder	12.5% 1/8 • Number of events 1 • From screening procedures (Day 0) to the end of the study (Day 28). Analysis of adverse events (AEs) was performed on TEAEs, defined as AEs that started at or after treatment start (for the poractant alfa group) or at or after randomisation (for the control group). Safety set (SAF) was used to evaluate AEs and serious AEs (SAEs). The SAF included all enrolled patients, except for one, who was randomised to receive poractant alfa was not treated. All patients included in the SAF were also included in the ITT.	0.00% 0/13 • From screening procedures (Day 0) to the end of the study (Day 28). Analysis of adverse events (AEs) was performed on TEAEs, defined as AEs that started at or after treatment start (for the poractant alfa group) or at or after randomisation (for the control group). Safety set (SAF) was used to evaluate AEs and serious AEs (SAEs). The SAF included all enrolled patients, except for one, who was randomised to receive poractant alfa was not treated. All patients included in the SAF were also included in the ITT.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/8 • From screening procedures (Day 0) to the end of the study (Day 28). Analysis of adverse events (AEs) was performed on TEAEs, defined as AEs that started at or after treatment start (for the poractant alfa group) or at or after randomisation (for the control group). Safety set (SAF) was used to evaluate AEs and serious AEs (SAEs). The SAF included all enrolled patients, except for one, who was randomised to receive poractant alfa was not treated. All patients included in the SAF were also included in the ITT.	15.4% 2/13 • Number of events 2 • From screening procedures (Day 0) to the end of the study (Day 28). Analysis of adverse events (AEs) was performed on TEAEs, defined as AEs that started at or after treatment start (for the poractant alfa group) or at or after randomisation (for the control group). Safety set (SAF) was used to evaluate AEs and serious AEs (SAEs). The SAF included all enrolled patients, except for one, who was randomised to receive poractant alfa was not treated. All patients included in the SAF were also included in the ITT.
Vascular disorders Deep vein thrombosis	12.5% 1/8 • Number of events 1 • From screening procedures (Day 0) to the end of the study (Day 28). Analysis of adverse events (AEs) was performed on TEAEs, defined as AEs that started at or after treatment start (for the poractant alfa group) or at or after randomisation (for the control group). Safety set (SAF) was used to evaluate AEs and serious AEs (SAEs). The SAF included all enrolled patients, except for one, who was randomised to receive poractant alfa was not treated. All patients included in the SAF were also included in the ITT.	0.00% 0/13 • From screening procedures (Day 0) to the end of the study (Day 28). Analysis of adverse events (AEs) was performed on TEAEs, defined as AEs that started at or after treatment start (for the poractant alfa group) or at or after randomisation (for the control group). Safety set (SAF) was used to evaluate AEs and serious AEs (SAEs). The SAF included all enrolled patients, except for one, who was randomised to receive poractant alfa was not treated. All patients included in the SAF were also included in the ITT.
Vascular disorders Hypotension	0.00% 0/8 • From screening procedures (Day 0) to the end of the study (Day 28). Analysis of adverse events (AEs) was performed on TEAEs, defined as AEs that started at or after treatment start (for the poractant alfa group) or at or after randomisation (for the control group). Safety set (SAF) was used to evaluate AEs and serious AEs (SAEs). The SAF included all enrolled patients, except for one, who was randomised to receive poractant alfa was not treated. All patients included in the SAF were also included in the ITT.	7.7% 1/13 • Number of events 1 • From screening procedures (Day 0) to the end of the study (Day 28). Analysis of adverse events (AEs) was performed on TEAEs, defined as AEs that started at or after treatment start (for the poractant alfa group) or at or after randomisation (for the control group). Safety set (SAF) was used to evaluate AEs and serious AEs (SAEs). The SAF included all enrolled patients, except for one, who was randomised to receive poractant alfa was not treated. All patients included in the SAF were also included in the ITT.