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.: PACTR202106915491232 Date of Approval: 21/06/2021
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title An Open Randomised Controlled Trial for Optimzing Antivenom Therapy Among Carpet Viper Envenomed Children in Northeastern Nigeria
Official scientific title Optimzing Antivenom Therapy Among Carpet Viper Envenomed Children in Northeastern Nigeria
Brief summary describing the background and objectives of the trial Snakebite envenoming (SBE) is a major problem in many countries in the rural tropics. Young people and children are commonly affected as bites often occur during farming and outdoor activities. In northeastern Nigeria carpet viper is the main cause of SBE . Antivenom remains the mainstay of therapy against SBE reducing mortality to less than 2% although it may be as high as 20% without antivenom therapy (Habib and Warrell, 2013). The recommended dose of an antivenom is derived from preclinical murine studies as the traditional phase II dose finding studies conducted among healthy adult humans are usually not done given the known risks of early adverse reactions (EAR) following administration of antivenoms which are animal derived heterologous plasma (Abubakar SB, et al., 2010). Generally, the same antivenom dose is adminstered to adults and children as snakes inject the same venom dose regardless of the victim’s age or size. Also, it is justified that the same dose should be administered as children have less protein to bind the circulating venom, smaller extracellular fluid volume and high venom to body mass ratio potentially leading to severer envenoming but also potentially higher risk of antivenom-related EAR in children compard to adults. Consequently, it is necessary to determine the basic minimum amount of antivenom that would be enough to reverse envenoming but equally to lead to the barest minimum risk of EAR and untoward effects. Here, we hpothesize 1 vial is non-inferior to 2 vials of EchiTab ICP Plus antivenom as regards effectiveness and that the lower volume may be safer. We will also determine the safety of intravenous slow bolus push compared to continuous infusion mode of administration among carpet viper envenomed children aged 1 to 12 years in Nigeria.
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Injury, Occupational Diseases, Poisoning
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Drugs
Anticipated trial start date 01/07/2021
Actual trial start date 01/07/2021
Anticipated date of last follow up 30/11/2021
Actual Last follow-up date 30/11/2021
Anticipated target sample size (number of participants) 80
Actual target sample size (number of participants) 80
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
Parallel: different groups receive different interventions at same time during study Randomised Permuted block randomization Sealed opaque envelopes Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group EchiTab ICP Plus antivenom 1 vial single dose 4 months The EchiTab ICP Plus antivenom was developed against three Nigerian snakes’ venoms – black African spitting cobra, puff adder and carpet viper. Each vial of 10mls contains an average of 40mg/ml of protein and it has been recommended that 3 vials should be administered against carpet viper envenoming for both adults and children based on preclinical murine experiments and dose finding study in mildly envenomed patients (Abubakar SB et al 2010). Subsequently, this dose was proven to be safe and effective among carpet viper envenomed patients in Nigeria (Abubakar IS et al 2010) with 83% restoring clotting within 6 hours and non-fatal EAR observed in 26% among nearly 200 patients. 40
Control Group EchiTab ICP Plus antivenom 2 vials single dose 4 months The EchiTab ICP Plus antivenom was developed against three Nigerian snakes’ venoms – black African spitting cobra, puff adder and carpet viper. Each vial of 10mls contains an average of 40mg/ml of protein and it has been recommended that 3 vials should be administered against carpet viper envenoming for both adults and children based on preclinical murine experiments and dose finding study in mildly envenomed patients (Abubakar SB et al 2010). Subsequently, this dose was proven to be safe and effective among carpet viper envenomed patients in Nigeria (Abubakar IS et al 2010) with 83% restoring clotting within 6 hours and non-fatal EAR observed in 26% among nearly 200 patients. 40 Dose Comparison
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1- Children aged 12 months to 12 years 2- Availability of intravenous access 3- Mild to moderately envenomed patients 4- Presentation within 72 hours of bite 1- Severely envenomed sick children that are or have: a. Collapsed or in unresponsive shock b. Grade III of the snakebite severity score c. Severe anaemia with packed cell volume (PCV) less than 12% d. Non-transient unconscious patients e. Patients with severe delayed gangrenous body part f. Suspicion of acute end-organ complications e.g., acute kidney injury (AKI) g. Other 2- Inability to obtain intravenous access for antivenom administration or blood collection 3- Children less than 12 months 4- Other severe co-morbidities Child: 6 Year-12 Year,Infant: 1 Month-23 Month,Preschool Child: 2 Year-5 Year 12 Month(s) 12 Year(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
No 14/06/2021 BAYERO UNIVERSITY KANO COLLEGE OF HEALTH SCIENCES RESEARCH ETHICS COMMITTEE
Ethics Committee Address
Street address City Postal code Country
No. 2 Hospital road, Aminu Kano Teaching Hospital, Kano Kano 70001 Nigeria
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome 1- Proportion who achieve restoration of blood clotting following 20WBCT at 6 hours and at 12 hours post antivenom administration 2- Proportion who develop features of early adverse reactions (EAR) post antivenom administration(s); patients will be actively observed for 60 minutes post administration 6 hours post antivenom administration
Secondary Outcome 1- The enrolled patients will be assessed for size of the bitten limb compared to the non-bitten limb pre-antivenom administration and thereafter daily. 2- Length of hospital stay in days and hours will recorded 3- All patients who die or develop life threatening complications (e.g., limb amputation) will be recorded 4- Proportion who develop late serum reactions in all enrolled groups 5- ELISA measurements of venom antigen and antivenom antibody (or fragment) level Daily
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Snakebite Research and Treatment Hospital Hospital road Kaltungo Kaltungo Gombe State Nigeria
FUNDING SOURCES
Name of source Street address City Postal code Country
Venom Antivenom Research Project Bayero University Kano B.U.K road Kano Kano Nigeria
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Venom Antivenom Research Project Bayero University Kano B.U.K road, Kano Kano Nigeria University
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Hamza Muhammad drhamza1020@ymail.com +2348035053139 B.U.K road, Kano
City Postal code Country Position/Affiliation
Kano 70001 Nigeria Associate Professor of Medicine
Role Name Email Phone Street address
Public Enquiries Hamza Muhammad drhamza1020@ymail.com +2348035053139 B.U.K road Kano
City Postal code Country Position/Affiliation
Kano 70001 Nigeria Associate Professor of Medicine
Role Name Email Phone Street address
Scientific Enquiries Hamza Muhammad drhamza1020@ymail.com +2348035053139 B.U.K road Kano
City Postal code Country Position/Affiliation
Kano 70001 Nigeria Associate Professor of Medicine
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes On completion of the research, the following will be done: 1. The report will be circulated to stakeholders; stakeholders include the Hospital, Ministries of Health Bauchi and Gombe states and Federal Ministries of Health. 2. The results will be published in reputable peer reviewed journals. 3. Also, copies of the report will be widely disseminated to libraries of the Teaching Hospitals, Colleges of Medicine and postgraduate medical colleges across Nigeria to ensure that health Professionals are aware of the study findings. 4. Reports and publications will also be given/shared to Bayero University Kano and WHO who recently designated snakebite as a Neglected Tropical Disease and civil society organizations working on snakebite. Informed Consent Form,Statistical Analysis Plan,Study Protocol 6 months after completion of trial The baseline characteristics between those administered one and two antivenom vials and between those administered bolus compared to slow antivenom infusion will be compared using wilcoxson ranksum test or student’s t-test for quantitative variables while Fisher’s test will be used for comparison of categoric variables. Measures of effect will be computed for comparisons i.e., the Relative Risk with respective one-sided 95% Confidence Interval, RR [95%CI]. Data will be analyzed both by Intention To Treat (ITT) and On Treatment (OT) analyses. As a non-inferiority study one-sided 95% Confidence Intervals will be derived for assessing treatment effects of categoric and quantitative variables’ comparisons.
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