Neonatal EncephalopathyPhase 2NCT06098833
Treatment of Neonatal Encephalopathy With Oral Sildenafil Suspension to Repair Brain Injury Secondary to Birth Asphyxia
A Phase 2 study testing Sildenafil and Ora-Blend in people with Neonatal Encephalopathy, run by Pia Wintermark at 3 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 0 minutes to 48 hours
- Conditions the study is for
- Neonatal Encephalopathy
- What is being tested?
- Sildenafil and Ora-Blend
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 1 Jul 2024to Oct 2031
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 minutes to 48 hours
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
- 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). 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.
Who cannot join
- 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
Trial locations and contacts
3 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
3 sites in 2 countries
Canada2 sites, 2 recruiting
- Recruiting
Montreal Children's Hospital
Montreal, Quebec, H3C 0T3
Pia Wintermark, MD, +1-514-512-4452, pia.wintermark@mcgill.ca
Gabriel Altit, MD, 1-514-412-4452, gabriel.altit@mcgill.ca
- Recruiting
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, H3T 1C5
Anie Lapointe, MD, 1-514-345-4931 ext. 5122, anie.lapointe.med@ssss.gouv.qc.ca
Sophie Tremblay, MD, 1-514-345-4931 ext. 4500, sophie.tremblay.med1@ssss.gouv.qc.ca
United States1 site, 1 recruiting
- Recruiting
Children's Hospital Colorado
Denver, Colorado, 80045
Sunah Hwang, MD, PhD, MPH/MSPH, 303-724-2846, Sunah.hwang@childrenscolorado.org
Sunah Hwang, MD, PhD, MPH/MSPH
About this study
Official title: Treatment of Neonatal Encephalopathy With Oral Sildenafil Suspension to Repair Brain Injury Secondary to Birth Asphyxia: A Randomized, Double-blind, Placebo-controlled Clinical Trial to Evaluate Safety and Efficacy (Phase II Study)
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.
Read the detailed description
The investigators will enroll neonates with HIE treated with TH from NICUs in a multicentre, randomized, double-blind, placebo-controlled phase 2 clinical trial to evaluate the safety and efficacy of sildenafil to repair brain injury. Neonates with moderate-severe HIE on admission and with brain injury on a day-2 brain MRI (during TH) will be randomized to sildenafil or placebo (allocation 2:1) for 7 consecutive days.
Aim 1: Evaluate the efficacy of sildenafil to improve brain injury (primary outcome). The investigators will determine whether sildenafil reduces brain injury on a day-30 MRI compared to the baseline day-2 MRI.
Aim 2: Determine the safety of sildenafil (secondary outcome). The investigators will assess the safety of sildenafil by recording the incidence of adverse events.
Aim 3: Evaluate the efficacy of sildenafil to improve cardiopulmonary hemodynamics (secondary outcome). The investigators will determine whether sildenafil improves pulmonary pressure and right/left ventricular function on day 4 of life (after TH completion) compared to baseline day-2 measurements
- Conditions
- Neonatal Encephalopathy
- Being tested
- Sildenafil, Ora-Blend
- Keywords
- birth asphyxia, brain, hypoxic-ischemic encephalopathy, neonate, neuroprotection, neurorestoration, newborn, sildenafil
- Medical subject headings
- Asphyxia Neonatorum, Hypoxia-Ischemia, Brain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SildenafilDrug
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)
Ora-BlendDrug
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)
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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) Receives: Drug: Ora-Blend |
What is being measured
The primary outcome is the main question the study is designed to answer.
Extent of brain injury
Primary outcome to explore efficacy (brain injury)
Measured: Day 30 of life, compared to day 2 of life
Secondary outcomes (1)
Serious adverse events
Close monitoring for adverse events such as death, hypotension, persistent pulmonary hypertension, altered renal or hepatic function, etc to assess the safety of sildenafil
Measured: Day 1 to 10 of life
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2023
- Study start1 Jul 2024
- Primary completionOct 2030 (estimated)
- Study completionOct 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neonatal EncephalopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Pia Wintermark
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Pia Wintermark, McGill University Health Centre/Research Institute of the McGill University Health Centre
- Investigators
- Pia Wintermark, MD, Principal investigator, Research Institute of the McGill University Health Centre (The Institute)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06098833
- Sponsor's protocol ID
- SANE-03
- Status last verified
- Sep 2026
- First submitted
- 18 Oct 2023
- Last updated
- 17 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No