CompletedPhase 2

Milrinone in Congenital Diaphragmatic Hernia

United States66 participantsStarted 2017-10-24

Plain-language summary

Infants with congenital diaphragmatic hernia (CDH) usually have pulmonary hypoplasia and persistent pulmonary hypertension of the newborn (PPHN) leading to hypoxemic respiratory failure (HRF). Pulmonary hypertension associated with CDH is frequently resistant to conventional pulmonary vasodilator therapy including inhaled nitric oxide (iNO). Increased pulmonary vascular resistance (PVR) can lead to right ventricular overload and dysfunction. In patients with CDH, left ventricular dysfunction, either caused by right ventricular overload or a relative underdevelopment of the left ventricle, is associated with poor prognosis. Milrinone is an intravenous inotrope and lusitrope (enhances cardiac systolic contraction and diastolic relaxation respectively) with pulmonary vasodilator properties and has been shown anecdotally to improve oxygenation in PPHN. Milrinone is commonly used during the management of CDH although no randomized trials have been performed to test its efficacy. Thirty percent of infants with CDH in the Children's Hospital Neonatal Database (CHND) and 22% of late-preterm and term infants with CDH in the Pediatrix database received milrinone. In the recently published VICI trial, 84% of patients with CDH received a vasoactive medication. In the current pilot trial, neonates with an antenatal or postnatal diagnosis of CDH will be randomized to receive milrinone or placebo to establish safety of this medication in CDH and test its efficacy in improving oxygenation.

Who can participate

Age range0 Hours – 168 Hours

SexALL

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Eligibility criteria: Infants are eligible if they meet all of the following criteria: * ≥ 36 0/7 weeks PMA by best obstetric estimate AND birth weight of ≥ 2000g * postnatal age ≤7 days (168 hours of age) * invasive mechanical ventilation (defined as ventilation with an endotracheal tube) and * one arterial blood gas with an OI ≥ 10 (after tracheal tube obstruction and other easily resolvable mechanical causes for increased OI are ruled out) on the most recent arterial blood gas within 12 hours prior to the time of randomization. * if an arterial blood gas is not available at the time of randomization, a preductal OSI of ≥ 5 can be used as an inclusion criterion instead of OI ≥ 10; (the OSI should be based on the most recent preductal pulse oximetry recording and must be within 12 hours of randomization) * postnatal blood gas with PCO2 ≤ 80 mmHg (arterial, capillary or venous blood gas) on the most recent blood gas sample obtained within 12 hours prior to randomization Note: Criteria (iv) to (vi) must be met at the most recent analysis within 12 hours prior to randomization. Exclusion Criteria: Infants are ineligible if they meet any of the following criteria: * known hypertrophic cardiomyopathy * Note 1: infants of diabetic mothers with asymmetric septal hypertrophy can be included as long as there is no evidence of obstruction to left ventricular outflow tract on echocardiogram, * Note 2: infants with other acyanotic congenital heart disease (CHD) and CDH may be …

What they're measuring

Oxygenation Response

Timeframe: 24 h after initiation of study drug

Trial details

NCT IDNCT02951130

SponsorNICHD Neonatal Research Network

Sponsor typeNETWORK

Study typeINTERVENTIONAL

Primary completion2024-09-30

Results submitted2025-09-30