Trial Outcomes & Findings for Milrinone in Congenital Diaphragmatic Hernia (NCT NCT02951130)

Results Overview

The primary outcome of this study is change in oxygenation from baseline (prior to study drug infusion) to 24 hours after initiation of study drug infusion. Oxygenation is assessed by oxygenation index (OI = mean airway pressure x oxygen concentration in % / PaO2 in mmHg). Oxygen saturation index (OSI = mean airway pressure x oxygen concentration in % / oxygen saturation in %) values were converted to OI values for this measure. Data are presented as OI at 24 hours minus OI at baseline. A negative value indicates improvement in oxygenation. A positive value indicates deterioration in oxygenation.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

66 participants

Primary outcome timeframe

24 h after initiation of study drug

Results posted on

2025-11-06

Participant Flow

Participant milestones

Participant milestones
Measure	Milrinone Milrinone infusion at 0.33µg/kg/min. The dose of the study drug will be increased to 0.66 µg/kg/min if oxygenation index (OI) remains ≥ 10 without any evidence of hypotension (as defined by the protocol) two hours after initiation of study drug. Infusion will be continued until the OI decreases to \< 7. The maximum duration of study drug infusion is 72 hours.	5% dextrose (D5W) An equivalent volume of 5% dextrose (D5W) will be used for infants randomized to the placebo arm.
Overall Study COMPLETED	32	32
Overall Study NOT COMPLETED	1	1
Overall Study STARTED	33	33

Reasons for withdrawal

Reasons for withdrawal
Measure	Milrinone Milrinone infusion at 0.33µg/kg/min. The dose of the study drug will be increased to 0.66 µg/kg/min if oxygenation index (OI) remains ≥ 10 without any evidence of hypotension (as defined by the protocol) two hours after initiation of study drug. Infusion will be continued until the OI decreases to \< 7. The maximum duration of study drug infusion is 72 hours.	5% dextrose (D5W) An equivalent volume of 5% dextrose (D5W) will be used for infants randomized to the placebo arm.
Overall Study Protocol Violation	1	1

Baseline Characteristics

Two participants did not receive any study drug.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Milrinone n=33 Participants Milrinone infusion at 0.33µg/kg/min. The dose of the study drug will be increased to 0.66 µg/kg/min if oxygenation index (OI) remains ≥ 10 without any evidence of hypotension (as defined by the protocol) two hours after initiation of study drug. Infusion will be continued until the OI decreases to \< 7. The maximum duration of study drug infusion is 72 hours.	5% dextrose (D5W) n=33 Participants An equivalent volume of 5% dextrose (D5W) will be used for infants randomized to the placebo arm.	Total n=66 Participants Total of all reporting groups
Age, Customized	14.4 hours n=32 Participants • Two participants did not receive any study drug.	19.6 hours n=32 Participants • Two participants did not receive any study drug.	16.9 hours n=64 Participants • Two participants did not receive any study drug.
Sex: Female, Male Female	17 Participants n=33 Participants	13 Participants n=33 Participants	30 Participants n=66 Participants
Sex: Female, Male Male	16 Participants n=33 Participants	20 Participants n=33 Participants	36 Participants n=66 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=33 Participants	9 Participants n=33 Participants	12 Participants n=66 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	29 Participants n=33 Participants	23 Participants n=33 Participants	52 Participants n=66 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=33 Participants	1 Participants n=33 Participants	2 Participants n=66 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=33 Participants	0 Participants n=33 Participants	0 Participants n=66 Participants
Race (NIH/OMB) Asian	0 Participants n=33 Participants	2 Participants n=33 Participants	2 Participants n=66 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=33 Participants	1 Participants n=33 Participants	1 Participants n=66 Participants
Race (NIH/OMB) Black or African American	1 Participants n=33 Participants	1 Participants n=33 Participants	2 Participants n=66 Participants
Race (NIH/OMB) White	30 Participants n=33 Participants	25 Participants n=33 Participants	55 Participants n=66 Participants
Race (NIH/OMB) More than one race	1 Participants n=33 Participants	0 Participants n=33 Participants	1 Participants n=66 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=33 Participants	4 Participants n=33 Participants	5 Participants n=66 Participants

PRIMARY outcome

Timeframe: 24 h after initiation of study drug

The primary outcome of this study is change in oxygenation from baseline (prior to study drug infusion) to 24 hours after initiation of study drug infusion. Oxygenation is assessed by oxygenation index (OI = mean airway pressure x oxygen concentration in % / PaO2 in mmHg). Oxygen saturation index (OSI = mean airway pressure x oxygen concentration in % / oxygen saturation in %) values were converted to OI values for this measure. Data are presented as OI at 24 hours minus OI at baseline. A negative value indicates improvement in oxygenation. A positive value indicates deterioration in oxygenation.

Outcome measures

Outcome measures
Measure	Milrinone n=32 Participants Milrinone infusion at 0.33µg/kg/min. The dose of the study drug will be increased to 0.66 µg/kg/min if oxygenation index (OI) remains ≥ 10 without any evidence of hypotension (as defined by the protocol) two hours after initiation of study drug. Infusion will be continued until the OI decreases to \< 7. The maximum duration of study drug infusion is 72 hours.	5% dextrose (D5W) n=32 Participants An equivalent volume of 5% dextrose (D5W) will be used for infants randomized to the placebo arm.
Oxygenation Response	4.2 Change in Oxygenation Index Interval -1.5 to 9.0	2.6 Change in Oxygenation Index Interval 0.0 to 9.6

SECONDARY outcome

Timeframe: 48 and 72 h after initiation of study drug

Oxygenation index at 48 and 72 h (or OI at the time of initiation of ECMO or immediately prior to death, for infants placed on ECMO or died before these time points)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Prior to initiation of study drug to between 24 and 72 hours after initiation of study drug

Changes in echocardiogram to assess pulmonary arterial pressure (as defined by protocol) between pre-study drug echocardiogram and echocardiogram obtained between 24 and 72 h after starting the study drug. The outcome will be available only for those infants who have a pre-study drug echocardiogram and a second echocardiogram between 24 and 72 hours after initiation of study drug performed for clinical reasons.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 72 hours after initiation of study drug

Vasoactive Inotrope Score is a quantitative assessment of the degree of therapeutic support required by the patient to maintain adequate perfusion and/or blood pressure.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: After initiation of the study drug at 4 time points per day - every 6 hours x 72 hours or discontinuation of study drug (whichever comes first)

Area under the curve for inspired oxygen after initiation of the study drug (inspired oxygen and ventilator data from 4 time points per day - every 6 hours will be recorded to calculate area under the curve)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Through 24 h post study drug initiation

If subsequent to the study drug, any additional inotrope or pulmonary vasodilator is used (such as iNO), we will evaluate the oxygenation response to these agents. If inotropes or vasodilators were used prior to the initiation of study drug, similar values will be recorded. The OI and PaO2/ FiO2 ratio prior to at least 30 min after initiation of the inotrope / vasodilator are recorded. The change in OI and PaO2/ FiO2 ratio in response to these agents is evaluated as a continuous variable and arbitrarily classified into responders, partial responders and non-responders

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 28 days and 56 days postnatal age (or discharge whichever comes first)

The use of supplemental oxygen at 28 d will be used to calculate the incidence of chronic lung disease. Chronic lung disease severity will be classified similar to the BPD classification in preterm infants at \> 32 week gestation.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Measured by no ECMO at time of hospital discharge or at the time the infant reaches 120 days of life and remains in the hospital, whichever comes earlier

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: All clinical status measures (as defined by protocol) will be obtained just prior to the infants discharge from the hospital and again at 12 months of age.

Clinical status - pulmonary (use of supplemental oxygen or respiratory medications - diuretics, methylxanthines, steroids, inhaled or nebulized steroids or bronchodilators) and nutritional (weight, length, head circumference, use of anti-reflux medications)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From initial recruitment: 16 patients enrolled per month to complete the trial in 4 years

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From initial recruitment: 16 patients enrolled per month to complete the trial in 4 years

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From initial recruitment: 16 patients enrolled per month to complete the trial in 4 years

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From initial recruitment: 16 patients enrolled per month to complete the trial in 4 years

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 24 h after initiation of study drug

Outcome measures

Outcome data not reported

Adverse Events

Milrinone

Serious events: 5 serious events

Other events: 5 other events

Deaths: 7 deaths

5% dextrose (D5W)

Serious events: 3 serious events

Other events: 2 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	Milrinone n=33 participants at risk Milrinone infusion at 0.33µg/kg/min. The dose of the study drug will be increased to 0.66 µg/kg/min if oxygenation index (OI) remains ≥ 10 without any evidence of hypotension (as defined by the protocol) two hours after initiation of study drug. Infusion will be continued until the OI decreases to \< 7. The maximum duration of study drug infusion is 72 hours.	5% dextrose (D5W) n=33 participants at risk An equivalent volume of 5% dextrose (D5W) will be used for infants randomized to the placebo arm.
Vascular disorders Shock	3.0% 1/33 • Number of events 1 • Study specified adverse events (AE) are monitored during the study (e.g. from treatment initiation through 24 hours after discontinuation of study drug infusion).	6.1% 2/33 • Number of events 2 • Study specified adverse events (AE) are monitored during the study (e.g. from treatment initiation through 24 hours after discontinuation of study drug infusion).
Respiratory, thoracic and mediastinal disorders Neonatal respiratory failure	12.1% 4/33 • Number of events 4 • Study specified adverse events (AE) are monitored during the study (e.g. from treatment initiation through 24 hours after discontinuation of study drug infusion).	6.1% 2/33 • Number of events 2 • Study specified adverse events (AE) are monitored during the study (e.g. from treatment initiation through 24 hours after discontinuation of study drug infusion).
Cardiac disorders Cardio-respiratory arrest neonatal	3.0% 1/33 • Number of events 1 • Study specified adverse events (AE) are monitored during the study (e.g. from treatment initiation through 24 hours after discontinuation of study drug infusion).	0.00% 0/33 • Study specified adverse events (AE) are monitored during the study (e.g. from treatment initiation through 24 hours after discontinuation of study drug infusion).
Nervous system disorders Haemorrhage intracranial	0.00% 0/33 • Study specified adverse events (AE) are monitored during the study (e.g. from treatment initiation through 24 hours after discontinuation of study drug infusion).	3.0% 1/33 • Number of events 1 • Study specified adverse events (AE) are monitored during the study (e.g. from treatment initiation through 24 hours after discontinuation of study drug infusion).

Other adverse events

Other adverse events
Measure	Milrinone n=33 participants at risk Milrinone infusion at 0.33µg/kg/min. The dose of the study drug will be increased to 0.66 µg/kg/min if oxygenation index (OI) remains ≥ 10 without any evidence of hypotension (as defined by the protocol) two hours after initiation of study drug. Infusion will be continued until the OI decreases to \< 7. The maximum duration of study drug infusion is 72 hours.	5% dextrose (D5W) n=33 participants at risk An equivalent volume of 5% dextrose (D5W) will be used for infants randomized to the placebo arm.
Nervous system disorders Haemorrhage intracranial	3.0% 1/33 • Number of events 1 • Study specified adverse events (AE) are monitored during the study (e.g. from treatment initiation through 24 hours after discontinuation of study drug infusion).	3.0% 1/33 • Number of events 1 • Study specified adverse events (AE) are monitored during the study (e.g. from treatment initiation through 24 hours after discontinuation of study drug infusion).
Vascular disorders Shock	12.1% 4/33 • Number of events 4 • Study specified adverse events (AE) are monitored during the study (e.g. from treatment initiation through 24 hours after discontinuation of study drug infusion).	3.0% 1/33 • Number of events 1 • Study specified adverse events (AE) are monitored during the study (e.g. from treatment initiation through 24 hours after discontinuation of study drug infusion).
Respiratory, thoracic and mediastinal disorders Neonatal respiratory failure	3.0% 1/33 • Number of events 1 • Study specified adverse events (AE) are monitored during the study (e.g. from treatment initiation through 24 hours after discontinuation of study drug infusion).	0.00% 0/33 • Study specified adverse events (AE) are monitored during the study (e.g. from treatment initiation through 24 hours after discontinuation of study drug infusion).

Additional Information

Satyan Lakshminrusimha

UC Davis School of Medicine

Phone: 916 734 5178

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place