Trial Outcomes & Findings for Inhaled Prostaglandin E1 (IPGE1) for Hypoxemic Respiratory Failure (NHRF) (NCT NCT01467076)

Results Overview

The primary outcome is the ability to recruit adequate number of infants (n=50) in a 9 month period without excessive (\>20%) protocol violations.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

7 participants

Primary outcome timeframe

From study start through 9 months after 75% of the participating sites are enrolling

Results posted on

2019-04-24

Participant Flow

Opened for recruitment on 10/20/2011. There was a lag of 33 to 90 days between IRB approval and site readiness to enroll patients. 46 infants were screened at 8 sites, 14 met eligibility criteria, and 7 were randomized. Enrollment was halted for lack of feasibility in mid-May 2012; at that time, only 7 patients had been enrolled.

Seven eligible infants were not enrolled because parents were unavailable or refused consent for 3 of the infants, 3 infants met ECMO criteria, and 1 had cardio-respiratory arrest.

Participant milestones

Participant milestones
Measure	Control Aerosolized saline	Low Dose IPGE1 150 ng/kg/min	High Dose IPGE1 300 ng/kg/min
Overall Study STARTED	3	2	2
Overall Study COMPLETED	2	2	2
Overall Study NOT COMPLETED	1	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Control Aerosolized saline	Low Dose IPGE1 150 ng/kg/min	High Dose IPGE1 300 ng/kg/min
Overall Study Lost to Follow-up	1	0	0

Baseline Characteristics

Inhaled Prostaglandin E1 (IPGE1) for Hypoxemic Respiratory Failure (NHRF)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Control n=3 Participants Aerosolized saline	Low Dose IPGE1 n=2 Participants 150 ng/kg/min	High Dose IPGE1 n=2 Participants 300 ng/kg/min	Total n=7 Participants Total of all reporting groups
Age, Customized Age at Randomization	41.75 hours n=5 Participants	11.30 hours n=7 Participants	26.65 hours n=5 Participants	28.73 hours n=4 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Birthweight	3591 grams n=5 Participants	3530 grams n=7 Participants	3320 grams n=5 Participants	3496 grams n=4 Participants
Delivery by Cesarean Section	2 participants n=5 Participants	2 participants n=7 Participants	1 participants n=5 Participants	5 participants n=4 Participants
Intubation in Delivery Room	0 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants	4 participants n=4 Participants

PRIMARY outcome

Timeframe: From study start through 9 months after 75% of the participating sites are enrolling

Population: Late preterm \& term infants ≤ 7 days postnatal age undergoing conventional ventilation (CNV) or high frequency oscillatory ventilation (HFOV) for NHRF (including perinatal aspiration syndrome, suspected/proven pneumonia/sepsis, respiratory distress syndrome, idiopathic PPHN or suspected pulmonary hypoplasia) with suboptimal response to INO

The primary outcome is the ability to recruit adequate number of infants (n=50) in a 9 month period without excessive (\>20%) protocol violations.

Outcome measures

Outcome measures
Measure	Control n=3 Participants Aerosolized saline	Low Dose IPGE1 n=2 Participants 150 ng/kg/min	High Dose IPGE1 n=2 Participants 300 ng/kg/min
Feasibility Assessed as the Number of Participants Who Were Enrolled in the Study	3 participants	2 participants	2 participants

SECONDARY outcome

Timeframe: Measurement of ABG at 60±15 minutes and 4±2 hours after start of study aerosol.

Population: To gauge the improvement in PaO2 for each group, the average of the difference between the two PaO2 ABG measurements (measurement at 4±2 hours-measurement at 60±15 minutes after start of study aerosol) and the range(minimum, maximum) of the differences between OI ABG measurements at the two time points within each group are presented here.

Changes in PaO2 based on the arterial blood gases (ABG) measurements obtained after 60 minutes and ABG obtained 4 hours after start of study aerosol.

Outcome measures

Outcome measures
Measure	Control n=3 Participants Aerosolized saline	Low Dose IPGE1 n=2 Participants 150 ng/kg/min	High Dose IPGE1 n=2 Participants 300 ng/kg/min
Change in Partial Pressure of Oxygen in the Blood (PaO2)	30 mmHg Interval -1.0 to 59.0	85 mmHg Interval 22.0 to 148.0	48 mmHg Interval -9.0 to 95.0

SECONDARY outcome

Timeframe: Measurement of ABG at 60±15 minutes and 4±2 hours after start of study aerosol.

Population: To gauge change in OI for each group we present both the average and the range of the difference between the two OI ABG measurements (measurement at 4±2 hours - measurement at 60±15 minutes after start of study aerosol). A positive difference indicates an increase in OI measurement; a negative difference indicates a decrease in OI measurement.

Change in OI based on the arterial blood gases (ABG) measurements obtained at 60±15 minutes and ABG obtained 4±2 hours after start of study aerosol.

Outcome measures

Outcome measures
Measure	Control n=3 Participants Aerosolized saline	Low Dose IPGE1 n=2 Participants 150 ng/kg/min	High Dose IPGE1 n=2 Participants 300 ng/kg/min
Change in Oxygenation Index (OI)	4 oxygenation index Interval -1.0 to 9.0	14 oxygenation index Interval 6.0 to 21.0	10 oxygenation index Interval -5.0 to 25.0

SECONDARY outcome

Timeframe: Date of first administration of INO to date of final discontinuation of INO

Population: Date of final discontinuation of INO was not available for 1 infant in the Control group and 1 infant in the LOW DOSE IPGE1 group

Administration of INO continued after the Infant was on INO for 72 hours

Outcome measures

Outcome measures
Measure	Control n=2 Participants Aerosolized saline	Low Dose IPGE1 n=1 Participants 150 ng/kg/min	High Dose IPGE1 n=2 Participants 300 ng/kg/min
Need for Inhaled Nitric Oxide (INO) 72 Hours After INO	1 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From date of first administration of INO to date of final discontinuation of INO.

Population: The date of final discontinuation of INO was recorded for 2 infants in the control group, 1 infant in the low dose and all 2 infants in the high dose group.

Duration the infant is on INO from initial administration of INO to final discontinuation of INO.

Outcome measures

Outcome measures
Measure	Control n=2 Participants Aerosolized saline	Low Dose IPGE1 n=1 Participants 150 ng/kg/min	High Dose IPGE1 n=2 Participants 300 ng/kg/min
Duration of iNO Therapy	59.02 hours Interval 44.95 to 73.08	18.57 hours Interval 18.57 to 18.57	56.22 hours Interval 50.35 to 62.08

SECONDARY outcome

Timeframe: From birth through status (death, transfer, or discharge).

Population: All 3 infants in the control group, 2 infant in the Low dose and 2 infants in the High dose IPGE1 groups have status data (death, transfer or discharge).

Deaths prior to discharge home.

Outcome measures

Outcome measures
Measure	Control n=3 Participants Aerosolized saline	Low Dose IPGE1 n=2 Participants 150 ng/kg/min	High Dose IPGE1 n=2 Participants 300 ng/kg/min
Death	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From after discontinuation of study aerosol through status (death, transfer, or discharge).

Population: All 3 infants in the control group, 2 infant in the Low dose and 2 infants in the High dose IPGE1 groups have data on ECMO use at the institution after discontinuation of study aerosol.

ECMO provided at the institution for the infant after discontinuation of study aerosol.

Outcome measures

Outcome measures
Measure	Control n=3 Participants Aerosolized saline	Low Dose IPGE1 n=2 Participants 150 ng/kg/min	High Dose IPGE1 n=2 Participants 300 ng/kg/min
Need for Extracorporeal Membrane Oxygenation (ECMO)	2 Participants	1 Participants	2 Participants

SECONDARY outcome

Timeframe: From birth through status (death, transfer or discharge)

Population: All 3 infants in the aerosolized saline group, and the 2 infants in the lower dose IPGE1 group and high dose IPGE1 Group have the number of days on mechanical ventilation from birth to death, transfer or discharge.

Duration the infant is on Mechanical Ventilation from birth through status (death, transfer or discharge)

Outcome measures

Outcome measures
Measure	Control n=3 Participants Aerosolized saline	Low Dose IPGE1 n=2 Participants 150 ng/kg/min	High Dose IPGE1 n=2 Participants 300 ng/kg/min
Duration of Mechanical Ventilation	22 Days Interval 17.0 to 30.0	8 Days Interval 4.0 to 11.0	16 Days Interval 13.0 to 19.0

SECONDARY outcome

Timeframe: From birth through status (death, transfer or discharge)

Population: All 3 infants in the aerosolized saline group, and the 2 infants in the lower dose IPGE1 group and high dose IPGE1 Group have the number of days on supplemental oxygen from birth to death, transfer or discharge.

Number of days from birth during which the FiO2 at some point was \> 0.21.

Outcome measures

Outcome measures
Measure	Control n=3 Participants Aerosolized saline	Low Dose IPGE1 n=2 Participants 150 ng/kg/min	High Dose IPGE1 n=2 Participants 300 ng/kg/min
Number of Days of Supplemental Oxygen (O2) Used	43 Days Interval 24.0 to 79.0	8 Days Interval 4.0 to 12.0	11 Days Interval 9.0 to 13.0

SECONDARY outcome

Timeframe: From birth to discharge home

Population: Two infants in the aerosolized saline group, and 2 infants in the lowd ose IPGE1 group and high dose IPGE1 Group were discharged home/chronic care.

Length of stay in hospital from birth to discharge home.

Outcome measures

Outcome measures
Measure	Control n=3 Participants Aerosolized saline	Low Dose IPGE1 n=2 Participants 150 ng/kg/min	High Dose IPGE1 n=2 Participants 300 ng/kg/min
Length of Hospital Stay	64 Days Interval 27.0 to 81.0	31 Days Interval 21.0 to 40.0	39 Days Interval 29.0 to 49.0

Adverse Events

Control

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

Low Dose IPGE1

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

High Dose IPGE1

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Control n=3 participants at risk Aerosolized saline	Low Dose IPGE1 n=2 participants at risk 150 ng/kg/min	High Dose IPGE1 n=2 participants at risk 300 ng/kg/min
Blood and lymphatic system disorders Hypotension	33.3% 1/3 • Number of events 1 • Enrolled infants were monitored continuously throughout study aerosol administration and through 48 hours post study aerosol discontinuation for possible adverse effects of PGE1. Monitored adverse events (AEs) include arrhythmia, hypotension, seizures, bleeding tendency, diarrhea, and seizures.	0.00% 0/2 • Enrolled infants were monitored continuously throughout study aerosol administration and through 48 hours post study aerosol discontinuation for possible adverse effects of PGE1. Monitored adverse events (AEs) include arrhythmia, hypotension, seizures, bleeding tendency, diarrhea, and seizures.	0.00% 0/2 • Enrolled infants were monitored continuously throughout study aerosol administration and through 48 hours post study aerosol discontinuation for possible adverse effects of PGE1. Monitored adverse events (AEs) include arrhythmia, hypotension, seizures, bleeding tendency, diarrhea, and seizures.
Cardiac disorders Arrhythmia	0.00% 0/3 • Enrolled infants were monitored continuously throughout study aerosol administration and through 48 hours post study aerosol discontinuation for possible adverse effects of PGE1. Monitored adverse events (AEs) include arrhythmia, hypotension, seizures, bleeding tendency, diarrhea, and seizures.	0.00% 0/2 • Enrolled infants were monitored continuously throughout study aerosol administration and through 48 hours post study aerosol discontinuation for possible adverse effects of PGE1. Monitored adverse events (AEs) include arrhythmia, hypotension, seizures, bleeding tendency, diarrhea, and seizures.	0.00% 0/2 • Enrolled infants were monitored continuously throughout study aerosol administration and through 48 hours post study aerosol discontinuation for possible adverse effects of PGE1. Monitored adverse events (AEs) include arrhythmia, hypotension, seizures, bleeding tendency, diarrhea, and seizures.
Nervous system disorders New onset seizures	0.00% 0/3 • Enrolled infants were monitored continuously throughout study aerosol administration and through 48 hours post study aerosol discontinuation for possible adverse effects of PGE1. Monitored adverse events (AEs) include arrhythmia, hypotension, seizures, bleeding tendency, diarrhea, and seizures.	0.00% 0/2 • Enrolled infants were monitored continuously throughout study aerosol administration and through 48 hours post study aerosol discontinuation for possible adverse effects of PGE1. Monitored adverse events (AEs) include arrhythmia, hypotension, seizures, bleeding tendency, diarrhea, and seizures.	0.00% 0/2 • Enrolled infants were monitored continuously throughout study aerosol administration and through 48 hours post study aerosol discontinuation for possible adverse effects of PGE1. Monitored adverse events (AEs) include arrhythmia, hypotension, seizures, bleeding tendency, diarrhea, and seizures.
Blood and lymphatic system disorders New onset bleeding	0.00% 0/3 • Enrolled infants were monitored continuously throughout study aerosol administration and through 48 hours post study aerosol discontinuation for possible adverse effects of PGE1. Monitored adverse events (AEs) include arrhythmia, hypotension, seizures, bleeding tendency, diarrhea, and seizures.	0.00% 0/2 • Enrolled infants were monitored continuously throughout study aerosol administration and through 48 hours post study aerosol discontinuation for possible adverse effects of PGE1. Monitored adverse events (AEs) include arrhythmia, hypotension, seizures, bleeding tendency, diarrhea, and seizures.	0.00% 0/2 • Enrolled infants were monitored continuously throughout study aerosol administration and through 48 hours post study aerosol discontinuation for possible adverse effects of PGE1. Monitored adverse events (AEs) include arrhythmia, hypotension, seizures, bleeding tendency, diarrhea, and seizures.
Gastrointestinal disorders Diarrhea	0.00% 0/3 • Enrolled infants were monitored continuously throughout study aerosol administration and through 48 hours post study aerosol discontinuation for possible adverse effects of PGE1. Monitored adverse events (AEs) include arrhythmia, hypotension, seizures, bleeding tendency, diarrhea, and seizures.	0.00% 0/2 • Enrolled infants were monitored continuously throughout study aerosol administration and through 48 hours post study aerosol discontinuation for possible adverse effects of PGE1. Monitored adverse events (AEs) include arrhythmia, hypotension, seizures, bleeding tendency, diarrhea, and seizures.	0.00% 0/2 • Enrolled infants were monitored continuously throughout study aerosol administration and through 48 hours post study aerosol discontinuation for possible adverse effects of PGE1. Monitored adverse events (AEs) include arrhythmia, hypotension, seizures, bleeding tendency, diarrhea, and seizures.
Immune system disorders Fever	33.3% 1/3 • Number of events 1 • Enrolled infants were monitored continuously throughout study aerosol administration and through 48 hours post study aerosol discontinuation for possible adverse effects of PGE1. Monitored adverse events (AEs) include arrhythmia, hypotension, seizures, bleeding tendency, diarrhea, and seizures.	0.00% 0/2 • Enrolled infants were monitored continuously throughout study aerosol administration and through 48 hours post study aerosol discontinuation for possible adverse effects of PGE1. Monitored adverse events (AEs) include arrhythmia, hypotension, seizures, bleeding tendency, diarrhea, and seizures.	0.00% 0/2 • Enrolled infants were monitored continuously throughout study aerosol administration and through 48 hours post study aerosol discontinuation for possible adverse effects of PGE1. Monitored adverse events (AEs) include arrhythmia, hypotension, seizures, bleeding tendency, diarrhea, and seizures.

Other adverse events

Adverse event data not reported

Additional Information

Beena Sood, M.D.

Wayne State University

Phone: 313-745-5638

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Investigators must adhere to the Neonatal Research Network Publication policies.
Publication restrictions are in place

Restriction type: OTHER