Finding Solutions to Thrive After Birth Asphyxia in Africa (SANE-Uganda)

Finding Solutions to Thrive After Birth Asphyxia in Africa: An Open-label Dose-finding Clinical Trial (Phase Ib Study)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Birth Asphyxia
• Intervention / Treatment: Drug: Sildenafil

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• Uganda
  • Kawempe, Uganda
    • Kawempe National Referral Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 1 year (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sildenafil	Drug: Sildenafil; 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum tolerable dose of sildenafil	within 30 days of drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events (Safety and Tolerability)	safety, assessed through the reporting of adverse events, such as death, hypotension, persistent pulmonary hypertension, altered hepatic function, seizures, intraventricular and/or intraparenchymal hemorrhage	within 30 days of drug administration
Sildenafil concentrations		within 30 days of drug administration

Collaborators and Investigators

• Sponsor: Pia Wintermark
• Collaborators: Walimu; Kawempe National Referral Hospital; Saint Francis Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2022
• Primary Completion (Estimated): January 31, 2025
• Study Completion (Estimated): January 31, 2025

Study Registration Dates

• First Submitted: February 8, 2022
• First Submitted That Met QC Criteria: March 2, 2022
• First Posted (Actual): March 11, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 27, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Pathologic Processes; Infant, Newborn, Diseases; Death; Asphyxia; Asphyxia Neonatorum; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Vasodilator Agents; Urological Agents; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Sildenafil Citrate
• Other Study ID Numbers: SANE-Uganda

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No individual participant data sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No