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

Primary Purpose

Neonatal Encephalopathy

Status
Not yet recruiting
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Sildenafil
Ora-Blend
Sponsored by
Pia Wintermark
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neonatal Encephalopathy focused on measuring birth asphyxia, brain, hypoxic-ischemic encephalopathy, neonate, neuroprotection, neurorestoration, newborn, sildenafil

Eligibility Criteria

0 Minutes - 48 Hours (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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. 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 Moribund infants not expected to survive

Sites / Locations

  • Montreal Children's Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Sildenafil

Ora-Blend

Arm Description

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-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)

Outcomes

Primary Outcome Measures

Extent of brain injury
Primary outcome to explore efficacy (brain injury)

Secondary Outcome Measures

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

Full Information

First Posted
October 18, 2023
Last Updated
October 23, 2023
Sponsor
Pia Wintermark
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1. Study Identification

Unique Protocol Identification Number
NCT06098833
Brief Title
Treatment of Neonatal Encephalopathy With Oral Sildenafil Suspension to Repair Brain Injury Secondary to Birth Asphyxia
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)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 2023 (Anticipated)
Primary Completion Date
October 2027 (Anticipated)
Study Completion Date
June 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Pia Wintermark

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neonatal Encephalopathy
Keywords
birth asphyxia, brain, hypoxic-ischemic encephalopathy, neonate, neuroprotection, neurorestoration, newborn, sildenafil

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Sildenafil
Arm Type
Active Comparator
Arm Description
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)
Arm Title
Ora-Blend
Arm Type
Placebo Comparator
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
Sildenafil
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
Ora-Blend
Intervention Description
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)
Primary Outcome Measure Information:
Title
Extent of brain injury
Description
Primary outcome to explore efficacy (brain injury)
Time Frame
Day 30 of life, compared to day 2 of life
Secondary Outcome Measure Information:
Title
Serious adverse events
Description
Close monitoring for adverse events such as death, hypotension, persistent pulmonary hypertension, altered renal or hepatic function, etc to assess the safety of sildenafil
Time Frame
Day 1 to 10 of life
Other Pre-specified Outcome Measures:
Title
Ejection fraction (EF) in % (reflecting left ventricular function) and tricuspid annular plane systolic excursion (TAPSE) in cm (reflecting right ventricular function)
Description
Secondary outcome to explore efficacy (cardiopulmonary hemodynamics)
Time Frame
Day 2 to 4 of life

10. Eligibility

Sex
All
Minimum Age & Unit of Time
0 Minutes
Maximum Age & Unit of Time
48 Hours
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. 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 Moribund infants not expected to survive
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Pia Wintermark, MD
Phone
+1-514-412-4452
Email
pia.wintermark@mcgill.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pia Wintermark, MD
Organizational Affiliation
Research Institute of the McGill University Health Centre
Official's Role
Principal Investigator
Facility Information:
Facility Name
Montreal Children's Hospital
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H3C 0T3
Country
Canada
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pia Wintermark, MD
Phone
+1-514-512-4452
Email
pia.wintermark@mcgill.ca

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://www.neobrainlab.org
Description
Description Related Info

Learn more about this trial

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

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