PMID- 34052232
OWN - NLM
STAT- MEDLINE
DCOM- 20211129
LR  - 20220726
IS  - 1097-6833 (Electronic)
IS  - 0022-3476 (Linking)
VI  - 237
DP  - 2021 Oct
TI  - 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.
PG  - 154-161.e3
LID - S0022-3476(21)00502-3 [pii]
LID - 10.1016/j.jpeds.2021.05.051 [doi]
AB  - 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% FiO(2)) 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.
CI  - Copyright (c) 2021 Elsevier Inc. All rights reserved.
FAU - Pierce, Christine M
AU  - Pierce CM
AD  - Pediatric and Neonatal Intensive Care, Great Ormond Street Hospital for Children, 
      London, United Kingdom. Electronic address: Christine.Pierce@gosh.nhs.uk.
FAU - Zhang, Min H
AU  - Zhang MH
AD  - Global Biometrics and Data Management, Pfizer Inc, La Jolla, CA.
FAU - Jonsson, Baldvin
AU  - Jonsson B
AD  - Department of Neonatology, Karolinska Institute and University Hospital, 
      Stockholm, Sweden.
FAU - Iorga, Dinu
AU  - Iorga D
AD  - Pfizer Inc, Collegeville, PA.
FAU - Cheruvu, Narayan
AU  - Cheruvu N
AD  - Pfizer Inc, Collegeville, PA.
FAU - Balagtas, Cecile C
AU  - Balagtas CC
AD  - Pfizer Inc, New York, NY.
FAU - Steinhorn, Robin H
AU  - Steinhorn RH
AD  - Rady Children's Hospital and University of California San Diego, San Diego, CA.
LA  - eng
SI  - ClinicalTrials.gov/NCT01720524
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
DEP - 20210527
PL  - United States
TA  - J Pediatr
JT  - The Journal of pediatrics
JID - 0375410
RN  - 0 (Endothelium-Dependent Relaxing Factors)
RN  - 0 (Vasodilator Agents)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - BW9B0ZE037 (Sildenafil Citrate)
SB  - IM
CIN - J Pediatr. 2022 Jul;246:285-286. PMID: 35447122
CIN - J Pediatr. 2022 Jul;246:284-285. PMID: 35447124
MH  - Administration, Inhalation
MH  - Double-Blind Method
MH  - Endothelium-Dependent Relaxing Factors/administration & dosage
MH  - Female
MH  - Humans
MH  - Infant, Newborn
MH  - Infusions, Intravenous
MH  - Male
MH  - Nitric Oxide/administration & dosage
MH  - Persistent Fetal Circulation Syndrome/*drug therapy
MH  - Sildenafil Citrate/*therapeutic use
MH  - Vasodilator Agents/*therapeutic use
OTO - NOTNLM
OT  - PPHN
OT  - infant
OT  - inhaled nitric oxide
OT  - placebo
OT  - sildenafil citrate
OT  - treatment failure
EDAT- 2021/05/31 06:00
MHDA- 2021/11/30 06:00
CRDT- 2021/05/30 20:42
PHST- 2020/10/22 00:00 [received]
PHST- 2021/05/20 00:00 [revised]
PHST- 2021/05/21 00:00 [accepted]
PHST- 2021/05/31 06:00 [pubmed]
PHST- 2021/11/30 06:00 [medline]
PHST- 2021/05/30 20:42 [entrez]
AID - S0022-3476(21)00502-3 [pii]
AID - 10.1016/j.jpeds.2021.05.051 [doi]
PST - ppublish
SO  - J Pediatr. 2021 Oct;237:154-161.e3. doi: 10.1016/j.jpeds.2021.05.051. Epub 2021 
      May 27.