Clinical trial NCT05275725: Finding Solutions to Thrive After Birth Asphyxia in Africa
Official title: Finding Solutions to Thrive After Birth Asphyxia in Africa: An Open-label Dose-finding Clinical Trial (Phase Ib Study)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Birth Asphyxia
Lead sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
Sponsor class: OTHER
Collaborators: name: Kawempe National Referral Hospital
name: Saint Francis Hospital
name: Walimu
First posted: 2022-03-11
Enrollment: 18
Sex: ALL
Minimum age (years): 0
Maximum age (years): 18
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Phase Ib open-label single-arm dose-finding clinical trial
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Maximum tolerable dose of sildenafil
timeFrame: within 30 days of drug administration
Secondary outcomes:
measure: Incidence of adverse events (Safety and Tolerability)
timeFrame: within 30 days of drug administration
measure: Sildenafil concentrations
timeFrame: within 30 days of drug administration
Other outcomes:
Locations:
city: Kawempe
country: Uganda
facility: Kawempe National Referral Hospital
Study officials:
References: