Sildenafil to Repair Brain Injury Secondary to Birth Asphyxia

NCT04169191 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: SANE-02
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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

Conditions

Birth Asphyxia

Outcome Measures

Primary Outcomes (2)

• Death

  Number of participants with death

  within first 10 days of life

• Hypotension

  Number of participants with hypotension

  within first 10 days of life

Secondary Outcomes (1)

• Peak Plasma Concentration (Cmax)

  within first 10 days of life

Study Arms (1)

Sildenafil

EXPERIMENTAL

Drug: Sildenafil Citrate

Interventions

Sildenafil Citrate DRUG

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

Sildenafil

Eligibility Criteria

• Age: 0 Days - 2 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• McGill University Health Centre/Research Institute of the McGill University Health Centre: lead

Study Sites (1)

Montreal Children's Hospital

Montreal, Quebec, H4A3J1, Canada

Location

Related Publications (1)

• Wintermark P, Lapointe A, Altit G, Steinhorn R, Rampakakis E, Meid AD, Burhenne J, Bajraktari-Sylejmani G, Khairy M, Adamo MT, Gilbert G, Toffoli D, Zavalkoff S, Luu TM, Hailu E, Haefeli WE. Testing Higher Doses of Sildenafil to Repair Brain Injury Secondary to Birth Asphyxia: An Open-Label Dose-Finding Phase 1b Clinical Trial-Sildenafil Administration to Treat Neonatal Encephalopathy-Study 02. J Pediatr. 2025 Oct;285:114701. doi: 10.1016/j.jpeds.2025.114701. Epub 2025 Jun 23.

  PMID: 40562301 DERIVED

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: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Pediatrics

Model Details: 3+3 design to escalate the sildenafil dose up to 6 mg/kg/day (3mg/kg/dose q12h)

Study Record Dates

• First Submitted: October 1, 2019
• First Posted: November 19, 2019
• Study Start: September 19, 2019
• Primary Completion: December 31, 2021
• Study Completion: December 1, 2024
• Last Updated: July 12, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)