NCT02812433

Sildenafil Administration to Treat Neonatal Encephalopathy

Sildenafil Administration to Treat Neonatal Encephalopathy (SANE) and Repair Brain Injury Secondary to Birth Asphyxia: A Randomized, Double-blind, Placebo-controlled Pilot Phase Ib Study

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 28 (actual)
• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre · Academic / Other
• Sex: All
• Age: 0 Minutes – 48 Hours
• Healthy volunteers: Not accepted

Summary

Despite improvements in neonatal care, birth asphyxia in term newborns remains a serious condition causing significant mortality and long-term morbidity, including cerebral palsy and mental retardation. Currently, no treatment exists to repair brain injuries secondary to neonatal asphyxia. The only available treatment for this condition is hypothermia that may prevent but not repair the development of brain injury. The success of this therapy is limited. Sildenafil already is used with some newborns for other purposes (i.e., persistent pulmonary hypertension), but, surprisingly, its effect on the newborn brain has never been studied systematically. The findings of the investigators in the rat model of term neonatal encephalopathy demonstrated that the administration of sildenafil following asphyxia promotes brain injury recovery. Thus, the investigators hypothesize that sildenafil may improve neurodevelopmental outcome in term asphyxiated newborns, in whom hypothermia treatment has failed to prevent the development of brain injury.

Detailed description

Before being able to run a large multicenter randomized trial to prove this hypothesis, the investigators need to run a phase Ib pilot trial to ensure the feasibility and safety of using sildenafil in this population of newborns. Thus, for this phase Ib study, the investigators hypothesize that sildenafil can be safely used with term asphyxiated newborns treated with hypothermia. The investigators will test this hypothesis with the following specific aims: 1. Safety (primary): ensure that sildenafil can be safely used in asphyxiated newborns treated with hypothermia; 2. Tolerability (secondary): study the pharmacokinetics and pharmacodynamics of sildenafil in these newborns; 3. Efficacy (exploratory): determine whether sildenafil improves neurodevelopment at 2 years of age, decreases brain injury on day 30 of life and decreases neuroinflammation.

Conditions

• Neonatal Encephalopathy

Interventions

Type	Name	Description
DRUG	Sildenafil	sildenafil 2 mg/kg/dose per os twice a day for seven consecutive days (from day 2 of life to day 9 of life) if brain injury on day 2 of life
DRUG	Ora-Blend	Ora-Blend, 2 mg/kg/dose per os twice a day for seven consecutive days (from day 2 of life to day 9 of life) if brain injury on day 2 of life

Timeline

• Start date: 2016-07-01
• Primary completion: 2019-01-01
• Completion: 2022-01-01
• First posted: 2016-06-24
• Last updated: 2022-02-08

Locations

1 site across 1 country: Canada