Back to resultsSildenafil to Repair Brain Injury Secondary to Birth Asphyxia (SANE-02)
Primary Purpose
Birth Asphyxia
Status
Active
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
Sildenafil Citrate
Sponsored by
About this trial
This is an interventional treatment trial for Birth Asphyxia
Eligibility Criteria
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
Sites / Locations
- Montreal Children's Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Sildenafil
Arm Description
Outcomes
Primary Outcome Measures
Death
Number of participants with death
Hypotension
Number of participants with hypotension
Secondary Outcome Measures
Peak Plasma Concentration (Cmax)
Peak Plasma Concentration (Cmax)
Full Information
NCT ID
NCT04169191
First Posted
October 1, 2019
Last Updated
October 16, 2023
Sponsor
McGill University Health Centre/Research Institute of the McGill University Health Centre
1. Study Identification
Unique Protocol Identification Number
NCT04169191
Brief Title
Sildenafil to Repair Brain Injury Secondary to Birth Asphyxia
Acronym
SANE-02
Official Title
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)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 19, 2019 (Actual)
Primary Completion Date
December 31, 2021 (Actual)
Study Completion Date
June 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
McGill University Health Centre/Research Institute of the McGill University Health Centre
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
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Birth Asphyxia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
3+3 design to escalate the sildenafil dose up to 6 mg/kg/day (3mg/kg/dose q12h)
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Sildenafil
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Sildenafil Citrate
Intervention Description
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
Primary Outcome Measure Information:
Title
Death
Description
Number of participants with death
Time Frame
within first 10 days of life
Title
Hypotension
Description
Number of participants with hypotension
Time Frame
within first 10 days of life
Secondary Outcome Measure Information:
Title
Peak Plasma Concentration (Cmax)
Description
Peak Plasma Concentration (Cmax)
Time Frame
within first 10 days of life
10. Eligibility
Sex
All
Minimum Age & Unit of Time
0 Days
Maximum Age & Unit of Time
2 Days
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Montreal Children's Hospital
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H4A3J1
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
No plan to make individual participant data (IPD) available to other researchers
Learn more about this trial
Sildenafil to Repair Brain Injury Secondary to Birth Asphyxia
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