Sildenafil to Repair Brain Injury Secondary to Birth Asphyxia (SANE-02)

McGill University

Status and phase

Active, not recruiting

Phase 1

Conditions

Birth Asphyxia

Treatments

Drug: Sildenafil Citrate

Study type

Interventional

Funder types

Other

Identifiers

NCT04169191

SANE-02

Details and patient eligibility

About

The investigators will determine the maximum tolerable dose of sildenafil and establish the pharmacokinetic and pharmacodynamic profile of sildenafil in human asphyxiated neonates treated with hypothermia. They will use a 3+3 design to escalate the sildenafil dose up to 6 mg/kg/day (3mg/kg/dose q12h) in asphyxiated neonates demonstrating brain injury despite hypothermia treatment and assess whether we observe any beneficial effects of sildenafil on their brain and cardiopulmonary hemodynamics, without causing serious adverse events

Enrollment

20 estimated patients

Sex

All

Ages

Under 2 days old

Volunteers

No Healthy Volunteers

Inclusion criteria

Male and female neonates meeting the criteria for induced hypothermia:
- Gestational age ≥ 36 weeks and birth weight ≥ 1800 g;
- Evidence of fetal distress, i.e., history of an acute perinatal event, cord pH ≤ 7.0 or base deficit ≤ - 16 mEq/L;
- Evidence of neonatal distress, such as an Apgar score ≤ 5 at 10 minutes, postnatal blood gas pH obtained within the first hour of life ≤ 7.0 or base deficit ≤ - 16 mEq/L, or a continued need for ventilation initiated at birth and continued for at least 10 minutes;
- Evidence of moderate to severe neonatal encephalopathy by an abnormal neurological exam and/or an amplitude-integrated electroencephalogram (aEEG).
Evidence of brain injury on a brain magnetic resonance imaging (MRI) performed on day 2 of life.

Exclusion criteria

Neonates with complex congenital heart disease
Neonates with cerebral malformations
Neonates with genetic syndrome
Neonates with intraventricular and/or intraparenchymal hemorrhage on MRI performed on day 2 of life