A randomized, double-blind, placebo-controlled, prospective study of bosentan for the treatment of persistent pulmonary hypertension of the newborn

Abstract

Objective: To assess the efficacy and safety of bosentan as an adjuvant therapy of persistent pulmonary hypertension of the newborn (PPHN).Study Design: Forty-seven neonates with PPHN were randomly assigned to receive either bosentan (n ¼ 24) or placebo (n ¼ 23). Efficacy was evaluated with a favorable outcome defined as fulfilling all the following criteria (for example, oxygenation index <15, normal pulmonary artery pressure (<20 mm Hg) and no premature discontinuation of the drug because of drug-related toxicity or lack of efficacy). Evaluation of safety was done by monitoring drug-related adverse events.Result: Bosentan treatment was superior to placebo with a favorable response in 87.5% of patients treated with bosentan as compared with 20% of those who received placebo (P<0.0001). None of patients in the bosentan group had drug-related clinical or laboratory adverse events. Conclusion:Bosentan may be a useful adjuvant therapy of PPHN.

Standardized Postnatal Management of Infants with Congenital Diaphragmatic Hernia in Europe: The CDH EURO Consortium Consensus - 2015 Update

“…These agents have been used successfully in treating PPHN in neonates with and without CDH [44,45]. The effects of treatment may be best addressed by repeated cardiac evaluation [46].…”

Advances in Neonatal Pulmonary Hypertension

“…Two recent trials have shown that bosentan is well tolerated in neonates with PPHN. One single-center trial reported that bosentan led to substantial improvements in oxygenation in an iNO-naïve population of PPHN infants [67], but a subsequent multicenter trial (FUTURE-4) found that bosentan as adjunctive therapy for iNO did not improve PPHN outcomes, time on iNO or time to extubation, due possibly in part to inconsistent intestinal absorption [68]. …”

Prenatal Programming of Pulmonary Hypertension Induced by Chronic Hypoxia or Ductal Ligation in Sheep

“…75 Still, clinical studies with the nonselective ET-1 receptor blocker bosentan have showed promising results and demonstrate their therapeutic potential in adults 76,77 and possibly newborns. 78 Ductal ligation and chronic hypoxia both enhance ET-1-mediated pulmonary vascular contraction in sheep. Ivy et al 79 showed that in the ovine fetus, ductal ligation increased ET-1 content 3-fold, while ET-1 receptor activity was altered to promote vasoconstriction.…”