Finding Solutions to Thrive After Birth Asphyxia in Africa

NCT05275725 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: SANE-Uganda
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Birth Asphyxia

Outcome Measures

Primary Outcomes (1)

• Maximum tolerable dose of sildenafil

  within 30 days of drug administration

Secondary Outcomes (2)

• Incidence of adverse events (Safety and Tolerability)

  within 30 days of drug administration

• Sildenafil concentrations

  within 30 days of drug administration

Study Arms (1)

Sildenafil

EXPERIMENTAL

Drug: Sildenafil

Interventions

Sildenafil DRUG

Dose group 1st dose 2nd dose 3rd dose 4-14th doses Treatment Total dose/day frequency dose/day Group 1: #1-14=2 mg/kg q12h (4 mg/kg/day) Group 2: #1 = 2 mg/kg, #2-14 = 2.5 mg/kg q12h (5 mg/kg/day) Group 3: #1 = 2 mg/kg, #2 = 2.5 mg/kg, #3-14 = 3 mg/kg q12h (6 mg/kg/day) Group 4: #1 = 2.5 mg/kg, #2-14 = 3 mg/kg q12h (6 mg/kg/day) Group 5: #1-14 = 3 mg/kg q12h (6 mg/kg/day)

Sildenafil

Eligibility Criteria

• Age: 0 Days - 18 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Pia Wintermark: lead
• Kawempe National Referral Hospital: collaborator
• Saint Francis Hospital: collaborator
• Walimu: collaborator

Study Sites (1)

Kawempe National Referral Hospital

Kawempe, Uganda

Location

MeSH Terms

Conditions

Asphyxia Neonatorum

Interventions

Sildenafil Citrate

Condition Hierarchy (Ancestors)

Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Pediatrics

Model Details: Phase Ib open-label single-arm dose-finding clinical trial

Study Record Dates

• First Submitted: February 8, 2022
• First Posted: March 11, 2022
• Study Start: July 1, 2022
• Primary Completion: January 31, 2025
• Study Completion: January 31, 2025
• Last Updated: December 31, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

UG (1)