title: Randomised controlled double-blind non-inferiority trial of two antivenoms for saw-scaled or carpet viper (Echis ocellatus) envenoming in Nigeria.
abstract: 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.
authors.affiliation: Department of Community Medicine, Bayero University of Kano, Kano, Nigeria.
authors.forename: Isa S
authors.initials: IS
authors.lastname: Abubakar
authors.forename: Saidu B
authors.initials: SB
authors.lastname: Abubakar
authors.forename: Abdulrazaq G
authors.initials: AG
authors.lastname: Habib
authors.forename: Abdulsalam
authors.initials: A
authors.lastname: Nasidi
authors.forename: Nandul
authors.initials: N
authors.lastname: Durfa
authors.forename: Peter O
authors.initials: PO
authors.lastname: Yusuf
authors.forename: Solomon
authors.initials: S
authors.lastname: Larnyang
authors.forename: John
authors.initials: J
authors.lastname: Garnvwa
authors.forename: Elijah
authors.initials: E
authors.lastname: Sokomba
authors.forename: Lateef
authors.initials: L
authors.lastname: Salako
authors.forename: R David G
authors.initials: RD
authors.lastname: Theakston
authors.forename: Ed
authors.initials: E
authors.lastname: Juszczak
authors.forename: Nicola
authors.initials: N
authors.lastname: Alder
authors.forename: David A
authors.initials: DA
authors.lastname: Warrell
mesh_terms: 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
chemical_list: D000997:Antivenins; D014757:Viper Venoms