Sildenafil to Repair Brain Injury Secondary to Birth Asphyxia (SANE-02)

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)

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

Study Overview

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

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montréal, Quebec, Canada, H4A3J1
      • Montreal Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 2 days (Child)
• Accepts Healthy Volunteers: No

Description

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 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 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Plasma Concentration (Cmax)	Peak Plasma Concentration (Cmax)	within first 10 days of life

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2019
• Primary Completion (Actual): December 31, 2021
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: October 1, 2019
• First Submitted That Met QC Criteria: November 18, 2019
• First Posted (Actual): November 19, 2019

Study Record Updates

• Last Update Posted (Actual): October 17, 2023
• Last Update Submitted That Met QC Criteria: October 16, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Infant, Newborn, Diseases; Craniocerebral Trauma; Trauma, Nervous System; Death; Brain Injuries; Asphyxia; Asphyxia Neonatorum; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate
• Other Study ID Numbers: SANE-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No plan to make individual participant data (IPD) available to other researchers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No