Pierce Christine M, Zhang Min H, Jonsson Baldvin, Iorga Dinu, Cheruvu Narayan, Balagtas Cecile C, Steinhorn Robin H
Pediatric and Neonatal Intensive Care, Great Ormond Street Hospital for Children, London, United Kingdom.
Global Biometrics and Data Management, Pfizer Inc, La Jolla, CA.
J Pediatr. 2021 Oct;237:154-161.e3. doi: 10.1016/j.jpeds.2021.05.051. Epub 2021 May 27.
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.
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) 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.
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.
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.
探讨在吸入一氧化氮（iNO）基础上加用西地那非对患有新生儿持续性肺动脉高压（PPHN）或有PPHN风险的低氧性呼吸衰竭（HRF）的新生儿的疗效和安全性。
一项多国、随机、双盲、安慰剂对照试验的A部分。年龄≤96小时、胎龄>34周、因PPHN或有PPHN风险的HRF而接受iNO治疗（在≥50%的吸入氧浓度下为10 - 20 ppm）且氧合指数>15至<60的婴儿，被随机（1:1）分为静脉注射（IV）西地那非组（负荷剂量：0.1 mg/kg，30分钟以上；维持剂量：0.03 mg/kg/h）或安慰剂组，治疗长达14天。共同主要终点为治疗失败率（第14天/出院时）和未出现治疗失败的情况下使用iNO的时间。次要终点包括机械通气时间和氧合指标。
在87名筛查的婴儿中，29名被随机分配至IV西地那非组，30名被分配至安慰剂组；13名中断治疗（西地那非组，n = 6；安慰剂组：n = 7），包括3例死亡（西地那非组：n = 2；安慰剂组：n = 1）。西地那非组的治疗失败率（27.6%）与安慰剂组（20.0%；P = 0.4935）无差异。使用iNO的平均时间在西地那非组（4.1天）与安慰剂组（4.1天；P = 0.9850）之间无差异。次要终点未观察到差异。西地那非组最常见的不良事件（≥10%的婴儿）为低血压（n = 8/29）、低钾血症（n = 7/29）、贫血、药物戒断综合征（各n = 4/29）和心动过缓（n = 3/29）。1例严重不良事件（低血压）被认为与治疗相关。
对于患有PPHN或有PPHN风险的HRF的婴儿，在iNO基础上加用IV西地那非并不优于安慰剂。对不良事件的审查未发现任何表明IV西地那非存在安全问题的事件模式。婴儿将进行发育随访（B部分）。试验注册：CLINICALTRIALS.GOV：NCT01720524。
