Dataset Information

Safety of sildenafil in extremely premature infants: a phase I trial.

ABSTRACT:

Objective

To characterize the safety of sildenafil in premature infants.

Study design

A phase I, open-label trial of sildenafil in premature infants receiving sildenafil per usual clinical care (cohort 1) or receiving a single IV dose of sildenafil (cohort 2). Safety was evaluated based on adverse events (AEs), transaminase levels, and mean arterial pressure monitoring.

Results

Twenty-four infants in cohort 1 (n = 25) received enteral sildenafil. In cohort 2, infants received a single IV sildenafil dose of 0.25 mg/kg (n = 7) or 0.125 mg/kg (n = 2). In cohort 2, there was one serious AE related to study drug involving hypotension associated with a faster infusion rate than specified by the protocol. There were no AEs related to elevated transaminases.

Conclusion

Sildenafil was well tolerated by the study population. Drug administration times and flush rates require careful attention to prevent infusion-related hypotension associated with faster infusions of IV sildenafil in premature infants.

Clinical trial

ClinicalTrials.gov Identifier: NCT01670136.

SUBMITTER: Jackson W

PROVIDER: S-EPMC8569839 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Safety of sildenafil in extremely premature infants: a phase I trial.

Jackson Wesley W Gonzalez Daniel D Smith P Brian PB Ambalavanan Namasivayam N Atz Andrew M AM Sokol Gregory M GM Hornik Chi D CD Stewart Dan D Mundakel Gratias G Poindexter Brenda B BB Ahlfeld Shawn K SK Mills Mary M Cohen-Wolkowiez Michael M Martz Karen K Hornik Christoph P CP Laughon Matthew M MM

Journal of perinatology : official journal of the California Perinatal Association 20211105 1

<h4>Objective</h4>To characterize the safety of sildenafil in premature infants.<h4>Study design</h4>A phase I, open-label trial of sildenafil in premature infants receiving sildenafil per usual clinical care (cohort 1) or receiving a single IV dose of sildenafil (cohort 2). Safety was evaluated based on adverse events (AEs), transaminase levels, and mean arterial pressure monitoring.<h4>Results</h4>Twenty-four infants in cohort 1 (n = 25) received enteral sildenafil. In cohort 2, infants receiv ...[more]

PMID: 34741102

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Project description:BackgroundPulmonary 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.MethodsWe 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.DiscussionSildenafil 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.Trial registrationClinicalTrials.gov NCT04447989 . Registered 25 June 2020.

Dataset Information

Safety of sildenafil in extremely premature infants: a phase I trial.

Objective

Study design

Results

Conclusion

Clinical trial

Publications

Safety of sildenafil in extremely premature infants: a phase I trial.

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