Randomised controlled double-blind non-inferiority trial of two antivenoms for saw-scaled or carpet viper (Echis ocellatus) envenoming in Nigeria.
BACKGROUND
In West Africa, envenoming by saw-scaled or carpet vipers (Echis ocellatus) causes great morbidity and mortality, but there is a crisis in supply of effective and affordable antivenom (ISRCTN01257358).


METHODS
In a randomised, double-blind, controlled, non-inferiority trial, "EchiTAb Plus-ICP" (ET-Plus) equine antivenom made by Instituto Clodomiro Picado was compared to "EchiTAb G" (ET-G) ovine antivenom made by MicroPharm, which is the standard of care in Nigeria and was developed from the original EchiTAb-Fab introduced in 1998. Both are caprylic acid purified whole IgG antivenoms. ET-G is monospecific for Echis ocellatus antivenom (initial dose 1 vial) and ET-Plus is polyspecific for E. ocellatus, Naja nigricollis and Bitis arietans (initial dose 3 vials). Both had been screened by pre-clinical and preliminary clinical dose-finding and safety studies. Patients who presented with incoagulable blood, indicative of systemic envenoming by E. ocellatus, were recruited in Kaltungo, north-eastern Nigeria. Those eligible and consenting were randomly allocated with equal probability to receive ET-Plus or ET-G. The primary outcome was permanent restoration of blood coagulability 6 hours after the start of treatment, assessed by a simple whole blood clotting test repeated 6, 12, 18, 24 and 48 hr after treatment. Secondary (safety) outcomes were the incidences of anaphylactic, pyrogenic and late serum sickness-type antivenom reactions.


RESULTS
Initial doses permanently restored blood coagulability at 6 hours in 161/194 (83.0%) of ET-Plus and 156/206 (75.7%) of ET-G treated patients (Relative Risk [RR] 1.10 one-sided 95% CI lower limit 1.01; P = 0.05). ET-Plus caused early reactions on more occasions than did ET-G [50/194 (25.8%) and 39/206 (18.9%) respectively RR (1.36 one-sided 95% CI 1.86 upper limit; P = 0.06). These reactions were classified as severe in 21 (10.8%) and 11 (5.3%) of patients, respectively.


CONCLUSIONS
At these doses, ET-Plus was slightly more effective but ET-G was slightly safer. Both are recommended for treating E. ocellatus envenoming in Nigeria.


BACKGROUND
Current Controlled Trials ISRCTN01257358.
Abubakar
Isa S
IS
Department of Community Medicine, Bayero University of Kano, Kano, Nigeria.
Abubakar
Saidu B
SB
Habib
Abdulrazaq G
AG
Nasidi
Abdulsalam
A
Durfa
Nandul
N
Yusuf
Peter O
PO
Larnyang
Solomon
S
Garnvwa
John
J
Sokomba
Elijah
E
Salako
Lateef
L
Theakston
R David G
RD
Juszczak
Ed
E
Alder
Nicola
N
Warrell
David A
DA
D000293:Adolescent; D000328:Adult; D000818:Animals; D000997:Antivenins / Q000008:administration & dosage* / Q000009:adverse effects; D001780:Blood Coagulation Tests; D002648:Child; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009549:Nigeria; D011041:Poisoning / Q000628:therapy*; D016896:Treatment Outcome; D014757:Viper Venoms / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D017819:Viperidae; D055815:Young Adult
D000997:Antivenins; D014757:Viper Venoms