Efficacy and Safety of IV Sildenafil in the Treatment of Newborn Infants with, or at Risk of, Persistent Pulmonary Hypertension of the Newborn (PPHN): A Multicenter, Randomized, Placebo-Controlled Trial - 22/09/21
, Min H. Zhang, PhD 2, Baldvin Jonsson, MD, PhD 3, Dinu Iorga, MD 4, Narayan Cheruvu, PhD 4, Cecile C. Balagtas, PhD 5, Robin H. Steinhorn, MD 6Abstract |
Objective |
To investigate the efficacy and safety of sildenafil added to inhaled nitric oxide (iNO) for newborn infants with persistent pulmonary hypertension of newborn (PPHN) or hypoxic respiratory failure (HRF) at risk of PPHN.
Study design |
Part A of a multinational, randomized, double-blind, placebo-controlled trial. Infants ≤96 hours’ old, >34 weeks of gestation, receiving iNO (10-20 ppm on ≥50% FiO2) for PPHN or HRF at risk of PPHN, and oxygen index >15 to <60, were randomized (1:1) to intravenous (IV) sildenafil (loading: 0.1 mg/kg, over 30 minutes; maintenance: 0.03 mg/kg/h) or placebo, for up to 14 days. Coprimary end points were treatment failure rate (day 14/discharge) and time on iNO without treatment failure. Secondary end points included time on ventilation and oxygenation measures.
Results |
Of 87 infants screened, 29 were randomized to IV sildenafil and 30 to placebo; 13 discontinued treatment (sildenafil, n = 6; placebo: n = 7), including 3 deaths (sildenafil: n = 2; placebo: n = 1). Treatment failure rates did not differ with sildenafil (27.6%) vs placebo (20.0%; P = .4935). Mean time on iNO was not different with sildenafil (4.1 days) vs placebo (4.1 days; P = .9850). No differences were noted in secondary end points. Most common adverse events (AEs) with sildenafil (≥10% infants) were hypotension (n = 8/29), hypokalemia (n = 7/29), anemia, drug withdrawal syndrome (n = 4/29, each), and bradycardia (n = 3/29). One serious AE (hypotension) was considered treatment-related.
Conclusions |
IV sildenafil added to iNO was not superior to placebo in infants with PPHN or HRF at risk of PPHN. A review of AEs did not identify any pattern of events indicative of a safety concern with IV sildenafil. Infants will have developmental follow-up (Part B).
Trial registration Clinicaltrials.gov |
NCT01720524.
Le texte complet de cet article est disponible en PDF.Keywords : sildenafil citrate, PPHN, placebo, infant, inhaled nitric oxide, treatment failure
Abbreviations : AE, ECMO, HRF, iNO, ITT, IV, OI, PAH, PDE5, PPHN, SAE
Plan
| Study A1481316 was sponsored by Pfizer. The study sponsor (Pfizer) provided the intravenous sildenafil, financial support for the clinical research nurse and other costs of conducting the study at each site, as well as ongoing site monitoring. No honoraria or other payments were provided to the authors in relation to the manuscript. M.Z., D.I., N.C., and C.B. are full-time employees of Pfizer. R.S. serves an Associate Editor for The Journal of Pediatrics. The other authors declare no conflicts of interest. |
Vol 237
P. 154 - octobre 2021 Retour au numéro
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