Pilot Study to Assess Effectiveness of Milrinone in Congenital Diaphragmatic Hernia

syringe, medicine, glass bottle
syringe, medicine, glass bottle
A pilot study will assess the effectiveness of milrinone in a small group of infants born with congenital diaphragmatic hernia.

A nationwide team of researchers is currently recruiting for a pilot study (ClinicalTrials.gov Identifier: NCT02951130) that will assess the effectiveness of milrinone infusion therapy for oxygenation improvement among newborns ≥36 weeks postmenstrual age (PMA) with congenital diaphragmatic hernia (CDH), according to a paper published in Maternal Health, Neonatology and Perinatology.

Anecdotal evidence suggests milrinone, an intravenous inotrope and lusitrope, improves oxygenation in pulmonary hypertension (PH) associated with CDH. Considering CDH-PH may be resistant to pulmonary vasodilator therapy, the researchers of this proposed pilot seek to assess the oxygenation response to milrinone therapy vs placebo in 66 infants with CDH in a multicenter, masked, and randomized trial. Infants included in this study are projected to have an oxygenation index ≥10 or oxygen saturation index ≥5.

In addition, the researchers of this trial will include a follow-up phone questionnaire at 4, 8, and 12 months of age to determine pulmonary and nutritional status of infants with CDH. Either milrinone or placebo infusions will be initiated at a rate of 0.33 μg/kg/min, with an increase to 0.66 μg/kg/min if no evidence of hypotension is found 2 to 4 hours following the first infusion dose.

Prior to the design of this pilot study, researchers collected data on pulmonary vasodilator management and outcome of patients with CDH (n=337) from 18 neonatal intensive care units associated with the Neonatal Research Network. Of these patients, a total of 275 were aged ≥36 weeks PMA and had been exposed to intravenous prostaglandin E1 (1%), intravenous epoprostenol (3%), inhaled epoprostenol (6%), milrinone (17%), sildenafil (17%), and inhaled nitric oxide (39%). The mean survival to hospital discharge in these patients was 71%, demonstrating the possible associated benefit of these hypertension therapies.

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According to the investigators, this pilot study will not be adequately powered to compare mortality rates between groups receiving milrinone or placebo.

The findings from this trial may result in a larger multicenter, international trial of 750 to 800 patients with CDH-PH, “where randomization is based on oxygenation status and echocardiographic criteria with a clinically meaningful outcome such as survival without [extracorporeal membrane oxygenation].”


Lakshminrusimha S, Keszler M, Kirpalani H, et al. Milrinone in congenital diaphragmatic hernia – a randomized pilot trial: study protocol, review of literature and survey of current practices. Matern Health Neonatol Perinatol. 2017;3:27.