Finding Solutions to Thrive After Birth Asphyxia in Africa: An Open-label Dose-finding Clinical Trial (Phase Ib Study)
Overview
- Phase
- Phase 1
- Intervention
- Sildenafil
- Conditions
- Birth Asphyxia
- Sponsor
- Pia Wintermark
- Enrollment
- 18
- Locations
- 1
- Primary Endpoint
- Maximum tolerable dose of sildenafil
- Status
- Active, not recruiting
- Last Updated
- last year
Overview
Brief Summary
Neonatal encephalopathy (NE) is the third leading cause of under 5-year mortality and contributes substantially to long-term neurological morbidity worldwide. In low-income countries (LICs), families often lack the resources to care for affected children. For those with disabilities, stigma is high, and social and emotional impacts are substantial. Improving our understanding of NE in LICs is crucial if intervention strategies are developed. Providing access to an affordable and easy-to-administer treatment after birth may improve survival, early brain development and later outcome, maximizing developmental potential.
The primary objective of this study is to investigate the feasibility, safety and tolerability of administering sildenafil as a neuroprotective/neurorestorative strategy to improve early brain development in a cohort of children with NE in Uganda.
Investigators
Pia Wintermark
Associate Professor of Pediatrics
McGill University Health Centre/Research Institute of the McGill University Health Centre
Eligibility Criteria
Inclusion Criteria
- •Male and female neonates meeting the criteria for birth asphyxia
- •Gestational age ≥ 36 weeks and birth weight ≥ 1800 g;
- •Admitted to Kawempe Hospital or Nsambya Hospital within 48 hours of life;
- •Need for continued resuscitation after birth and/or 5-minute Apgar score ≤5;
- •Evidence of neonatal encephalopathy by an abnormal neurological exam (modified Sarnat score of 2-3 or abnormal aEEG).
Exclusion Criteria
- •Absent heart rate at 10 minutes/imminent death
- •Neonates with major congenital malformations
- •Neonates with grade 3 AKI (serum creatinine rise ≥3x lowest previous creatinine or creatinine \> 2.5 mg/dL = 221 mcmol/L or receipt of dialysis)
- •Neonates with intraventricular and/or intraparenchymal hemorrhage on cranial ultrasound (cUS) performed on day 1-2 of life
- •Mother living permanently outside 20km radius of Kawempe Hospital or Nsambya Hospital
- •Neonates whose parents are unwilling or unable to give informed written consent to enter the study
Arms & Interventions
Sildenafil
Intervention: Sildenafil
Outcomes
Primary Outcomes
Maximum tolerable dose of sildenafil
Time Frame: within 30 days of drug administration
Secondary Outcomes
- Sildenafil concentrations(within 30 days of drug administration)
- Incidence of adverse events (Safety and Tolerability)(within 30 days of drug administration)