Safety of sildenafil in premature infants with severe bronchopulmonary dysplasia (SILDI-SAFE): a multicenter, randomized, placebo-controlled, sequential dose-escalating, double-masked, safety study.
Safety of sildenafil in premature infants with severe bronchopulmonary dysplasia (SILDI-SAFE): a multicenter, randomized, placebo-controlled, sequential dose-escalating, double-masked, safety study.
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DOI：
10.1186/s12887-020-02453-7
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发表时间：
2020-12-14
期刊：
影响因子：
2.4
通讯作者：
Jackson W
中科院分区：
文献类型：
--
作者：
Schneider S;Bailey M;Spears T;Esther CR Jr;Laughon MM;Hornik CP;Jackson W
肺动脉高压是支气管肺发育不良的致命并发症，是早产儿最常见的肺部疾病。尽管存在这些灾难性后果，但尚无基于证据的疗法可用于预防该人群的肺动脉高压。西地那非是美国食品和药物管理局批准的一种强效肺血管扩张剂，用于治疗成人肺动脉高压。临床前模型表明西地那非通过改善肺泡化和保留血管发育对早产肺产生有益影响。因此，西地那非可以通过减少肺血管重塑和降低肺血管阻力来预防与早产儿肺部疾病相关的肺动脉高压的发生。然而，需要临床试验证据。本研究由美国国立卫生研究院国家心肺和血液研究所支持，将产生西地那非在患有严重支气管肺发育不良且有肺动脉高压风险的早产儿群体中的安全性、药代动力学和初步有效性数据。我们设计了一项多中心、随机、安慰剂对照、序贯剂量递增、双盲的西地那非安全性试验，用于治疗患有严重支气管肺发育不良的早产儿。我们将 120 名胎龄 <29 周且月经后 32-40 周患有严重支气管肺发育不良的早产儿按照 3:1（西地那非：安慰剂）的剂量递增方法随机分为约 30 个临床中心的 3 个队列。参与者将接受长达 34 天的研究药物，随后进行 28 天的安全监测。主要结局是根据低血压发生率确定的安全性。次要结果包括西地那非的药代动力学和初步有效性，基于治疗期结束时超声心动图诊断是否存在肺动脉高压。西地那非是一种有前景的干预措施，可预防患有支气管肺发育不良的早产儿发生肺动脉高压。迫切需要专门针对早产儿设计的西地那非的临床试验。目前的研究将为有关西地那非对有肺动脉高压风险的早产儿的安全性的科学认识做出重大贡献。研究人员将使用该研究的结果来设计关键疗效试验。临床试验.govNCT04447989。注册日期为 2020 年 6 月 25 日。在线版本包含可在 10.1186/s12887-020-02453-7 获取的补充材料。
Pulmonary hypertension is a deadly complication of bronchopulmonary dysplasia, the most common pulmonary morbidity of prematurity. Despite these catastrophic consequences, no evidence-based therapies are available for the prevention of pulmonary hypertension in this population. Sildenafil is a potent pulmonary vasodilator approved by the US Food and Drug Administration for the treatment of pulmonary hypertension in adults. Preclinical models suggest a beneficial effect of sildenafil on premature lungs through improved alveolarization and preserved vascular development. Sildenafil may therefore prevent the development of pulmonary hypertension associated with lung disease of prematurity by reducing pulmonary vascular remodeling and lowering pulmonary vascular resistance; however, clinical trial evidence is needed. The present study, supported by the National Institutes of Health’s National Heart Lung and Blood Institute, will generate safety, pharmacokinetics, and preliminary effectiveness data on sildenafil in a population of premature infants with severe bronchopulmonary dysplasia at risk for pulmonary hypertension. We have designed a multicenter, randomized, placebo-controlled, sequential dose-escalating, double-masked, safety trial of sildenafil in premature infants with severe bronchopulmonary dysplasia. We will randomize 120 premature infants < 29 weeks gestational age with severe bronchopulmonary dysplasia at 32–40 weeks postmenstrual age in a dose-escalating approach 3:1 (sildenafil: placebo) sequentially into each of 3 cohorts at ~ 30 clinical sites. Participants will receive up to 34 days of study drug, followed by 28 days of safety monitoring. The primary outcome will be safety as determined by incidence of hypotension. Secondary outcomes will include pharmacokinetics and preliminary effectiveness of sildenafil based on presence or absence of pulmonary hypertension diagnosed by echocardiography at the end of treatment period. Sildenafil is a promising intervention to prevent the development of pulmonary hypertension in premature infants with bronchopulmonary dysplasia. Clinical trials of sildenafil specifically designed for premature infants are urgently needed. The current study will make substantial contributions to scientific knowledge of the safety of sildenafil in premature infants at risk for pulmonary hypertension. Results from the study will be used by investigators to inform the design of a pivotal efficacy trial. ClinicalTrials.govNCT04447989. Registered 25 June 2020. The online version contains supplementary material available at 10.1186/s12887-020-02453-7.
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影响因子：
2.5
作者：
Kim, Do-Hyun;Kim, Han-Suk;Choi, Jung-Hwan
通讯作者：
Choi, Jung-Hwan
DOI：
10.1038/jp.2017.49
发表时间：
2017-07
期刊：
Journal of perinatology : official journal of the California Perinatal Association
影响因子：
--
作者：
Jackson W;Hornik CP;Messina JA;Guglielmo K;Watwe A;Delancy G;Valdez A;MacArthur T;Peter-Wohl S;Smith PB;Tolia VN;Laughon MM
通讯作者：
Laughon MM
影响因子：
3.7
作者：
Collaco JM;Dadlani GH;Nies MK;Leshko J;Everett AD;McGrath-Morrow SA
通讯作者：
McGrath-Morrow SA
影响因子：
8
作者：
Khemani, Ekta;McElhinney, Doff B.;Mullen, Mary P.
通讯作者：
Mullen, Mary P.
影响因子：
2.9
作者：
Slaughter, J. L.;Pakrashi, T.;Shah, T. A.
通讯作者：
Shah, T. A.