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.: PACTR202308870380725 Date of Approval: 30/08/2023
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title TIBC-II: 2-Iminobiotin versus standard care in neonates with perinatal asphyxia in Kinshasa (DR Congo)
Official scientific title TIBC-II: Multicenter phase II trial comparing efficacy of 2-iminobiotin (2-IB) treatment with standard care in neonates ≥36 weeks gestational age with moderate to severe perinatal asphyxia in Kinshasa, DR Congo
Brief summary describing the background and objectives of the trial The primary objective of this randomized double-blind placebo-controlled clinical trial, is to investigate the short-term efficacy of 2-iminobiotin in newborns with moderate to severe perinatal asphyxia in a low-resource country. Background Perinatal asphyxia (PA), defined by the WHO as the failure to establish breathing at birth, is one of the primary causes of neonatal morbidity and mortality. It accounts for nearly 1 million neonatal deaths per year worldwide, and 98% of related deaths occur in low and middle income countries (LMIC). In addition, PA results in a significant burden of care due to long-term neurological disability and impairment and has a substantial social impact. Currently, there is no effective treatment available for PA in LMIC. Therefore, there is an urgent need for therapy that is safe and effective, and can be easily administered in a low resource setting. One promising therapy is 2-iminobiotin (2-IB), a biotin analogue and selective inhibitor of neuronal and inducible nitric oxide synthase. The safety and efficacy of 2-IB have been demonstrated in short and long-term animal models of PA. Phase IIa clinical trials of 2-IB in adults after out of hospital cardiac arrest and stroke, and in neonates with PA, showed that 2-IB is safe; no adverse effects related to the use of 2-IB were observed. In DR Congo, 2-IB was first studied in 2016 in a pilot study that investigated the safety, tolerability and pharmacokinetics of 2-IB in neonates with PA. The results published in 'Paediatric Drugs' (2020), prompted us to move to the present study. The primary objective of this randomised double-blind placebo-controlled phase IIb study, is to investigate the short-term efficacy of 2-IB in neonates with moderate to severe perinatal asphyxia in a low-resource country.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) TIBC II
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 01/09/2023
Actual trial start date 17/05/2024
Anticipated date of last follow up 01/03/2026
Actual Last follow-up date
Anticipated target sample size (number of participants) 86
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
CUK01 Sponsor
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
Parallel: different groups receive different interventions at same time during study Randomised Permuted block randomization Numbered containers Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group 2 iminobiotin 20 hours (6 doses every 4 hours) 2-Iminobiotin 0.75 mg/ml solution for infusion will be administered as a slow intravenous bolus administration, by umbilical venous catheter or peripheral infusion. Patients will receive 6 doses of 0.09 mg/kg bodyweight every 4 hours 43
Control Group Placebo 20 hours (6 doses every 4 hours) Placebo solution for infusion will be administered as a slow intravenous bolus administration, by umbilical venous catheter or peripheral infusion. Patients will receive 6 doses placebo every 4 hours 43 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Newborns with ≥ 36 weeks gestation with moderate to severe perinatal asphyxia with a Thompson score ≥ 7 and < 16 within 6 hours of birth 2. Possibility to start treatment within 6 hours after birth 1. Inability to insert an umbilical venous catheter or peripheral infusion for study medication administration. 2. Major congenital or chromosomal abnormalities, such as diaphragmatic hernia, omphalocele, trisomy 13 or trisomy 18 3. Birth weight< 1800 grams 4. Obvious signs of infection 5. Moribund patients New born: 0 Day-1 Month 0 Day(s) 0 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 11/04/2023 Ethics Committee School of Public Health University of Kinshasa
Ethics Committee Address
Street address City Postal code Country
B.P. 11850 Kin I Kinshasa NA Democratic Republic of the Congo
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Efficacy - The number of surviving patients with aEEG (Continuous Normal Voltage (CNV)) 36 hours after birth 36 hours after birth
Secondary Outcome Safety - Vital signs (heart rate, respiratory rate and non-invasive blood pressure) just before and 15 minutes after each dose of study medication
Secondary Outcome Safety - Vital signs (heart rate and respiratory rate) 24 hours, 36 hours and 48 hours after the first administration of study medication
Secondary Outcome Safety - Need for intervention for respiratory and circulatory reasons from baseline to 15 minutes after administration of study medication
Secondary Outcome Safety - The occurrence of (serious) adverse events from baseline to discharge from the NICU, with a maximum of 7 days after birth
Secondary Outcome Efficacy - Thompson score 12 hours, 24 hours, 36 hours and 48 hours after birth
Secondary Outcome Efficacy - The number of surviving patients with normal aEEG (CNV) 24 hours and 48 hours after birth
Secondary Outcome Efficacy - The number of patients with CNV or Discontinuous Normal Voltage (DNV) 24 hours, 36 hours and 48 hours after birth
Secondary Outcome Efficacy - The number of patients with a sleep-wake cycle (SWC) 36 hours after birth
Secondary Outcome Efficacy - The time it takes for CNV, DNV and SWC from baseline to discharge from the NICU, with a maximum of 7 days after birth
Secondary Outcome Efficacy - Presence of clinical seizures from baseline to discharge from the NICU, with a maximum of 7 days after birth
Secondary Outcome Efficacy - Epileptic burden of (sub)clinical seizures (observed by aEEG) and presence of epileptic status from baseline to discharge from the NICU, with a maximum of 7 days after birth
Secondary Outcome Efficacy - Use of anticonvulsant medications needed to control seizures from baseline to discharge from the NICU, with a maximum of 7 days after birth
Secondary Outcome Efficacy - Mortality at 7 days 7 days after birth
Secondary Outcome Efficacy - The ability to drink at 7 days after birth or at discharge from the hospital 7 days after birth or at discharge from the hospital
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
University Clinics Kinshasa J6XR 69V Kinshasa Democratic Republic of the Congo
Ngaliema Clinic M7PC 4CV Kinshasa Democratic Republic of the Congo
Saint Joseph Hospital J8MR HCR Kinshasa Democratic Republic of the Congo
FUNDING SOURCES
Name of source Street address City Postal code Country
VLIRUOS Vlaamse Interuniversitaire Raad Universitaire Ontwikkelingssamenwerking Julien Dillensplein 1 Brussels Belgium
Neurophyxia B.V. Onderwijsboulevard 225 s Hertogenbosch Netherlands
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor University Clinics Kinshasa J6XR 69V Kinshasa Democratic Republic of the Congo University Hospitals
COLLABORATORS
Name Street address City Postal code Country
KU Leuven Oude markt 13 Leuven Belgium
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Therese Biselele therese.biselele@unikin.ac.cd +243895082997 J6XR 69V
City Postal code Country Position/Affiliation
Kinshasa Democratic Republic of the Congo Department of Pediatrics dept. Neonatology University Clinics of Kinshasa
Role Name Email Phone Street address
Public Enquiries Therese Biselele therese.biselele@unikin.ac.cd +243895082997 J6XR 69V
City Postal code Country Position/Affiliation
Kinshasa Democratic Republic of the Congo Department of Pediatrics Neonatology University Clinics of Kinshasa
Role Name Email Phone Street address
Scientific Enquiries Therese Biselele therese.biselele@unikin.ac.cd +243895082997 J6XR 69V
City Postal code Country Position/Affiliation
Kinshasa Democratic Republic of the Congo Department of Pediatrics Neonatology University Clinics of Kinshasa
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Individual participant data that underlie the results reported in the article, after deidentification (text, tables, figures and appendices) Analytic Code,Statistical Analysis Plan,Study Protocol Beginning 3 months and ending 5 years following article publication Access: controlled (researchers who provide a methodologically sound proposal) Types of analysis: to achieve aims in the approved proposal Process: Proposal should be directed to the PI. To gain access, data requestors will need to sign a data access agreement. Data are available for 5 years at a third party website (link to be included)
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