Clinical trial of two new anti-snake venoms for the treatment of patients bitten by venomous snakes in Nigeria

ISRCTN	ISRCTN01257358
DOI	https://doi.org/10.1186/ISRCTN01257358
Protocol serial number	EC003/05
Sponsor	Federal Ministry of Health (Nigeria)
Funder	Federal Ministry of Health (Nigeria)

Submission date: 13/01/2009
Registration date: 18/02/2009
Last edited: 30/12/2020

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Injury, Occupational Diseases, Poisoning

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Isa Sadeeq Abubakar
Scientific

Department of Community Medicine
Bayero University Kano
Kano
700001
Nigeria

Study information

Primary study design	Interventional
Study design	Randomised controlled double blind non-inferiority trial
Secondary study design	Randomised controlled trial
Scientific title	Pre-clinical and clinical assessment of new anti-venoms for the treatments of patients envenomed by the saw-scaled or carpet viper (Echis ocellatus) in northern Nigeria
Study acronym	ECGECP
Study objectives	EchiTAb™ G and EchiTAb™ Plus have similar efficacy and safety profiles with South African Institute for Medical Research (SAIMR) anti-venom (Gold standard) in restoration of coagulation after envenomation from the bite of Echis ocellatus. Please note that as of 11/02/10 the primary outcome field of this trial have been updated. Please view the relevant field for more details.
Ethics approval(s)	1. National Agency for Food and Drug Adminstration and Control (NAFDAC), Nigeria, gave approval on the 12th February 2005 2. Gombe State Governmental Medical Research Ethical Committee gave approval on the 8th March 2005 (ref: MOH/ADM/S/909/V.I/11)
Health condition(s) or problem(s) studied	Snake bite
Intervention	EchiTAb™ Plus is produced by the Instituto Clodomiro Picado (ICP), University of Costa Rica in collaboration with the EchiTAb study group Nigeria/UK and Liverpool School of Tropical Medicine and University of Oxford. This is an equine trispecific anti-venom raised against the venoms of Nigerian E. ocellatus, Bitis arietans (puff adder) and Naja nigricollis (spitting cobra). These venoms were selected because, from a medical point of view, they are the three most important snake species in sub-Saharan Africa. The anti-venom is prepared by caprylic acid precipitation of non-IgG plasma proteins. Preclinical tests using WHO-approved methods showed these antivenoms to be as effective or almost as effective against E. ocellatus venom as the original ovine Fab fragment monospecific EchiTAb™. The final product is presented as a liquid in 10 ml vials with a 3 year expiry period. 30 ml EchiTAb™ Plus will be given to each participant. EchiTAb™ G, which was developed and produced by EchiTAb study group Nigeria/UK, in collaboration with Micropharm Ltd UK and Liverpool School School of Tropical Medicine and Hygiene, is a purified IgG prepared by caprylic acid precipitation of non-IgG plasma proteins similar to the Costa Rican anti-venom described above. The final preparation is a liquid 10 ml vial with a 3-year expiry time. 10 ml EchiTAb™ G will be given to each participant. Both anti-venoms are given through the intravenous route slowly (at the rate of 2 ml/minute). To ensure blinding however, sterile water is drawn into the syringe by the Hospital Pharmacist (who is not part of the research team) to making up to 40 ml of a mixture of anti-venom and sterile water. Once a patient has been enrolled into the study and allocated to one of the two treatment groups, 20-minute Whole Blood Clotting Time (20WBCT) test is done to establish coagulopathy. Once established, the anti-venom is given, six hours after which the 20WBCT is repeated to establish whether or not coagulation is restored. If restored, no anti-venom is given, but the same test is repeated 6-hourly for 48 hours, and the patient subsequently discharged if coagulation is sustained. However, in a situation where the blood during the 20WBCT after administration of anti-venom does not clot, a repeat dose of the anti-venom is given and the same process followed until coagulation is sustained for up to 48 hours. Note that immediately after administration of the anti-venom, observation is made for signs of early anaphylactic or pyrogenic reactions.
Intervention type	Drug
Phase	Phase II/III
Drug / device / biological / vaccine name(s)	EchiTAb™ G anti-venom, EchiTAb™ Plus anti-venom, South African Institute for Medical Research (SAIMR) anti-venom
Primary outcome measure(s)	Current information as of 11/02/10: Restoration of blood coagulability, measured 6 hours after the initial dose of antivenom is deemed the primary outcome and time point of main interest. Incoagulable blood, measured at baseline, is an eligibility criterion. To ensure that restoration of blood coagulability at 6 hr is not transient followed by recurrent envenoming, it is also checked at 12, 18, 24 and 48 hours after the initial dose of antivenom. Initial information at time of registration: Blood coagulability, measured at baseline, 6, 12, 18, 24 and 48 hours after treatment
Key secondary outcome measure(s)	1. Anaphylactic reaction, measured immediately after treatment with anti-venom 2. Pyrogenic reaction, measured immediately after treatment with anti-venom 3. Late serum sickness, measured 2 weeks after discharge
Completion date	28/12/2008

Eligibility

Participant type(s)	Patient
Age group	Other
Sex	All
Target sample size at registration	400
Total final enrolment	400
Key inclusion criteria	Patients of both sexes and all ages bitten by snakes provided that: 1. They had incoagulable blood as defined by 20 minutes whole blood clotting time, indicative in this area of systemic envenoming by E. ocellatus 2. They have been bitten within the previous 72 hours 3. They or their relatives give informed consent to admission, treatment and investigation
Key exclusion criteria	1. Patients who had received antisnake venom within the last 24 hours 2. Pregnant women 3. Patients with clinical features of severe envenoming (shock, massive bleeding, lateralising signs suggesting intracranial haemorrhage, etc.) who require urgent treatment with a large dose of anti-venom and resuscitation
Date of first enrolment	14/05/2005
Date of final enrolment	28/12/2008

Locations

Countries of recruitment

Nigeria

Study participating centre

Department of Community Medicine

Kano
700001
Nigeria

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	27/07/2010	30/12/2020	Yes	No

Editorial Notes

30/12/2020: The following changes have been made:
1. Publication reference added.
2. The final enrolment number has been added from the reference.