Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202202647130754 Date of Approval: 11/02/2022
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Finding solutions to thrive after birth asphyxia in Africa: An open-label dose-finding clinical trial (Phase Ib study) - SANE-Uganda
Official scientific title Finding solutions to thrive after birth asphyxia in Africa: An open-label dose-finding clinical trial (Phase Ib study) - SANE-Uganda
Brief summary describing the background and objectives of the trial Neonatal encephalopathy (NE) is the third leading cause of under 5-year mortality and contributes substantially to long-term neurological morbidity worldwide. In low-income countries (LICs), families often lack the resources to care for affected children. For those with disabilities, stigma is high, and social and emotional impacts are substantial. Improving our understanding of NE in LICs is crucial if we are to develop intervention strategies. Providing access to an affordable and easy-to-administer treatment after birth may improve survival, early brain development and later outcome, maximizing developmental potential. The primary objective of this study is to investigate the feasibility, safety and tolerability of administering sildenafil as a neuroprotective/neurorestorative strategy to improve early brain development in a cohort of children with NE in Uganda.
Type of trial CCT
Acronym (If the trial has an acronym then please provide) SANEUganda
Disease(s) or condition(s) being studied Neonatal Diseases
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Drugs
Anticipated trial start date 01/03/2022
Actual trial start date
Anticipated date of last follow up 30/06/2024
Actual Last follow-up date
Anticipated target sample size (number of participants) 30
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Crossover: all participants receive all interventions in different sequence during study Non-randomised Allocation was determined by the holder of the sequence who is situated off site Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group Sildenafil Group 1: #1-14=2 mg/kg q12h (4 mg/kg/day) 14 doses, dose given q12h, 7 days We will use the classical 3+3 design to escalate the sildenafil dose up to 6 mg/kg/day in these neonates and assess if we observe positive effects of sildenafil on their brain and cardiac hemodynamics, without causing significant adverse event Group 1: n=3-6 6 Active-Treatment of Control Group
Experimental Group Sildenafil Group 2: #1 = 2 mg/kg, #2-14 = 2.5 mg/kg q12h (5 mg/kg/day) 14 doses, dose given q12h, 7 days We will use the classical 3+3 design to escalate the sildenafil dose up to 6 mg/kg/day in these neonates and assess if we observe positive effects of sildenafil on their brain and cardiac hemodynamics, without causing significant adverse event Group 2: n=3-6 6
Experimental Group Sildenafil Group 3: #1 = 2 mg/kg, #2 = 2.5 mg/kg, #3-14 = 3 mg/kg q12h (6 mg/kg/day) 14 doses, dose given q12h, 7 days We will use the classical 3+3 design to escalate the sildenafil dose up to 6 mg/kg/day in these neonates and assess if we observe positive effects of sildenafil on their brain and cardiac hemodynamics, without causing significant adverse event Group 3: n=3-6 6
Experimental Group Sildenafil Group 4: #1 = 2.5 mg/kg, #2-14 = 3 mg/kg q12h (6 mg/kg/day) 14 doses, dose given q12h, 7 days We will use the classical 3+3 design to escalate the sildenafil dose up to 6 mg/kg/day in these neonates and assess if we observe positive effects of sildenafil on their brain and cardiac hemodynamics, without causing significant adverse event Group 4: n=3-6 6
Experimental Group Sildenafil Group 5: #1-14 = 3 mg/kg q12h (6 mg/kg/day) 14 doses, dose given q12h, 7 days We will use the classical 3+3 design to escalate the sildenafil dose up to 6 mg/kg/day in these neonates and assess if we observe positive effects of sildenafil on their brain and cardiac hemodynamics, without causing significant adverse event Group 5: n=3-18 6
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
- Male and female neonates meeting the criteria for birth asphyxia: - Gestational age ≥ 36 weeks and birth weight ≥ 1800 g; - Admitted to Kawempe Hospital or Nsambya Hospital within 48 hours of life; - Need for continued resuscitation after birth and/or 5-minute Apgar score ≤5; - Evidence of neonatal encephalopathy by an abnormal neurological exam (modified Sarnat score of 2-3 or abnormal aEEG). - Absent heart rate at 10 minutes/imminent death - Neonates with major congenital malformations - Neonates with grade 3 AKI (serum creatinine rise ≥3x lowest previous creatinine or creatinine > 2.5 mg/dL = 221 mcmol/L or receipt of dialysis) - Neonates with intraventricular and/or intraparenchymal hemorrhage on cranial ultrasound (cUS) performed on day 1-2 of life - Mother living permanently outside 20km radius of Kawempe Hospital or Nsambya Hospital - Neonates whose parents are unwilling or unable to give informed written consent to enter the study New born: 0 Day-1 Month 0 Day(s) 30 Day(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 06/11/2021 Uganda Virus Research Institute
Ethics Committee Address
Street address City Postal code Country
Plot 51-59, Nakiwogo Road, Entebbe, P.O. Box 49, Entebbe Entebbe na Uganda
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 31/08/2021 National Drug Authority
Ethics Committee Address
Street address City Postal code Country
Plot 19 Lumumba Avenue P.O. Box 23096 Kampala na Uganda
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 10/06/2021 Uganda National Council for Science and Technology
Ethics Committee Address
Street address City Postal code Country
Plot 6 Kimera Road, Ntinda, P.O. Box 6884 Kampala na Uganda
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Maximum tolerable dose within 30 days of drug administration
Secondary Outcome Sildenafil safety within 30 days of drug administration
Secondary Outcome Sildenafil pharmacokinetics and pharmacodynamics within 30 days of drug administration
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Kawempe National Referral Hospital Plo 1035/3883 Kawempe, Bombo Road, P.O. Box 3253 Kampala Uganda
St. Francis Hospital Nsambya Road Nsambya Hill/ Box 7146 Nsambya Rd Nsambya Uganda
FUNDING SOURCES
Name of source Street address City Postal code Country
Bill and Melinda Gates Foundation P.O. Box 23350 Seattle 98102 United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Research Institute of the McGill University Health Centre na Montreal Canada University
COLLABORATORS
Name Street address City Postal code Country
Dr Lorraine Oriokot P.O. Box 11010 Kampala Uganda
Dr Victoria Nakibuuka P.O. Box 7146 Kampala Uganda
Dr Nathan Kenya Mugisha Unit 4, Plot 5-7, Coral Crescent, Kololo Kampala Uganda
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Pia Wintermark pia.wintermark@mcgill.ca +15144124452 1001 Boul. Decarie, Site Glen, Block E, EM0.3244
City Postal code Country Position/Affiliation
Montreal Canada Associate Professor of Pediatrics
Role Name Email Phone Street address
Public Enquiries Pia Wintermark pia.wintermark@mcgill.ca +15144124452 1001 Boul. Decarie, Site Glen, Block E, EM0.3244
City Postal code Country Position/Affiliation
Montreal Canada Associate Professor of Pediatrics
Role Name Email Phone Street address
Scientific Enquiries Pia Wintermark pia.wintermark@mcgill.ca +15144124452 1001 Boul. Decarie, Site Glen, Block E, EM0.3244
City Postal code Country Position/Affiliation
Montreal Canada Associate Professor of Pediatrics
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes No individual participant data sharing Clinical Study Report After completion of the study Published results will be made available
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information