Pilot Study to Assess Effectiveness of Milrinone in 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.

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].”

Reference

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.