Treatment of Neonatal Encephalopathy With Oral Sildenafil Suspension to Repair Brain Injury Secondary to Birth Asphyxia

NCT06098833 | Recruiting Phase 2 DMC

• 1 other identifier: SANE-03
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

Brief Summary

Around the time of birth, some babies experience a condition called asphyxia, which means that their brain and other organs do not receive enough blood and/or oxygen to work properly. This life-threatening condition accounts for nearly 1 out of 4 deaths of all babies around the world, and often leads to severe brain damage, cerebral palsy, epilepsy, and trouble with learning and functioning in everyday life. At this time, no treatment is available to repair the brain damage caused by asphyxia. Excitingly, a drug called sildenafil (Viagra®) is already given safely to babies who suffer from increased blood pressure in their lungs' vessels. Recent studies using a laboratory model of asphyxia at birth suggest that sildenafil may also repair the brain damage caused by asphyxia. Similarly, recent small studies have shown that it is both feasible and safe to give sildenafil to human babies, who suffered from asphyxia at birth. These studies also highlight the first promising signs that sildenafil may improve how the brains of these babies work, which is consistent with the abovementioned laboratory studies. On the basis of these previous researches, the investigators predict that sildenafil can repair the damage to a baby's brain. The investigators will test whether sildenafil can be safely given to a large group of human babies who suffer from asphyxia at birth, and will confirm whether sildenafil improves or not how their brains and hearts/lungs work. This project will enable to determine whether sildenafil is a promising treatment for repairing brain damage in babies who suffer from asphyxia at birth. This project may also provide new solutions for these babies to improve their future life.

Conditions

Neonatal Encephalopathy

Keywords

birth asphyxia; brain; hypoxic-ischemic encephalopathy; neonate; neuroprotection; neurorestoration; newborn; sildenafil

Outcome Measures

Primary Outcomes (1)

• Extent of brain injury

  Primary outcome to explore efficacy (brain injury)

  Day 30 of life, compared to day 2 of life

Secondary Outcomes (1)

• Serious adverse events

  Day 1 to 10 of life

Other Outcomes (1)

• Ejection fraction (EF) in % (reflecting left ventricular function) and tricuspid annular plane systolic excursion (TAPSE) in cm (reflecting right ventricular function)

  Day 2 to 4 of life

Study Arms (2)

Sildenafil

ACTIVE COMPARATOR

Sildenafil per os twice a day for seven consecutive days (from day 2 of life to day 9 of life) if brain injury on day 2 of life (dose 1=2mg/kg/dose, dose 2=2.5mg/kg/dose, and doses 3-14=3mg/kg/dose)

Drug: Sildenafil

Ora-Blend

PLACEBO COMPARATOR

Ora-Blend per os twice a day for seven consecutive days (from day 2 of life to day 9 of life) if brain injury on day 2 of life (dose 1=2mg/kg/dose, dose 2=2.5mg/kg/dose, and doses 3-14=3mg/kg/dose)

Drug: Ora-Blend

Interventions

Sildenafil DRUG

Sildenafil per os twice a day for seven consecutive days (from day 2 of life to day 9 of life) if brain injury on day 2 of life (dose 1=2mg/kg/dose, dose 2=2.5mg/kg/dose, and doses 3-14=3mg/kg/dose)

Sildenafil

Ora-Blend DRUG

Ora-Blend per os twice a day for seven consecutive days (from day 2 of life to day 9 of life) if brain injury on day 2 of life (dose 1=2mg/kg/dose, dose 2=2.5mg/kg/dose, and doses 3-14=3mg/kg/dose)

Ora-Blend

Eligibility Criteria

• Age: 0 Minutes - 48 Hours
• 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 ≥36weeks and birth weight ≥1800g;
• Evidence of fetal distress, i.e., history of an acute perinatal event, cord pH ≤7.0 or base deficit
• 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). They will receive whole-body cooling to an esophageal temperature of 33.5°C, initiated within the first 6 hours of life, continued for 72 hours, and then they will be slowly rewarmed using standard protocol.
• 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
• Moribund infants not expected to survive

Sponsors & Collaborators

• Pia Wintermark: lead

Study Sites (2)

Montreal Children's Hospital

Montreal, Quebec, H3C 0T3, Canada

RECRUITING

Centre Hospitalier Universitaire Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada

RECRUITING

Related Links

• Description Related Info

MeSH Terms

Conditions

Asphyxia Neonatorum; Hypoxia-Ischemia, Brain

Interventions

Sildenafil Citrate

Condition Hierarchy (Ancestors)

Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypoxia, Brain; Vascular Diseases; Cardiovascular Diseases; Hypoxia; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

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 Officials

• Pia Wintermark, MD

  Research Institute of the McGill University Health Centre (The Institute)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pia Wintermark, MD

CONTACT

+1-514-412-4452; pia.wintermark@mcgill.ca

Gabriel Altit, MD

CONTACT

+1-514-412-4452; gabriel.altit@mcgill.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Pediatrics

Study Record Dates

• First Submitted: October 18, 2023
• First Posted: October 25, 2023
• Study Start: July 1, 2024
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): June 1, 2028
• Last Updated: January 14, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2)