Sildenafil to Repair Brain Injury Secondary to Birth Asphyxia

Birth Asphyxia Clinical Trial

— SANE-02  

Official title:

Treatment of Neonatal Encephalopathy With Oral Sildenafil Suspension to Repair Brain Injury Secondary to Birth Asphyxia: An Open-label Dose-finding Clinical Trial (Phase Ib Study)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04169191
• Other study ID #: SANE-02
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: September 19, 2019
• Est. completion date: June 2024

Study information

• Verified date: October 2023
• Source: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 20
• Est. completion date: June 2024
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Days to 2 Days

Eligibility

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

Related Conditions & MeSH terms

• Asphyxia
• Asphyxia Neonatorum
• Birth Asphyxia
• Brain Injuries

Intervention

Drug:
• Sildenafil Citrate
Cohort 1 of 3-6 neonates: 1st dose of 2mg/kg/dose, 2nd dose of 2.5 mg/kg/dose, and subsequent doses of 2.5mg/kg/dose q12h (= 5 mg/kg/day from dose #2) Cohort 2 of 3-6 neonates: 1st dose of 2mg/kg/dose, 2nd dose of 2.5 mg/kg/dose, 3rd dose of 3mg/kg/dose, and subsequent doses of 3mg/kg/dose q12h (= 6 mg/kg/day from dose #3) dose expansion phase in up to 5-15 asphyxiated neonates

Locations

Country	Name	City	State
Canada	Montreal Children's Hospital	Montréal	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
McGill University Health Centre/Research Institute of the McGill University Health Centre

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Death	Number of participants with death	within first 10 days of life
Primary	Hypotension	Number of participants with hypotension	within first 10 days of life
Secondary	Peak Plasma Concentration (Cmax)	Peak Plasma Concentration (Cmax)	within first 10 days of life