Sildenafil to Repair Brain Injury Secondary to Birth Asphyxia

Phase 1

Active, not recruiting

• Conditions: Birth Asphyxia
• Interventions: Drug: Sildenafil Citrate

• Registration Number: NCT04169191
• Lead Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study Start: 2019-09-19
• Study First Submitted: 2019-10-01
• Study First Submitted QC: 2019-11-18
• Study First Posted: 2019-11-19
• Primary Completion: 2021-12-31
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-11
• Last Update Posted: 2024-07-12
• Study Completion: 2024-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 20

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Sildenafil	Sildenafil Citrate	-

Primary Outcome Measures

Name	Time	Method
Hypotension	within first 10 days of life	Number of participants with hypotension
Death	within first 10 days of life	Number of participants with death

Secondary Outcome Measures

Name	Time	Method
Peak Plasma Concentration (Cmax)	within first 10 days of life	Peak Plasma Concentration (Cmax)

Trial Locations

Locations (1)

Montreal Children's Hospital; 🇨🇦 Montréal, Quebec, Canada