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Clinical Trial
. 2017 Nov 27;11(11):e0006068.
doi: 10.1371/journal.pntd.0006068. eCollection 2017 Nov.

Safety and efficacy of a freeze-dried trivalent antivenom for snakebites in the Brazilian Amazon: An open randomized controlled phase IIb clinical trial

Affiliations
Clinical Trial

Safety and efficacy of a freeze-dried trivalent antivenom for snakebites in the Brazilian Amazon: An open randomized controlled phase IIb clinical trial

Iran Mendonça-da-Silva et al. PLoS Negl Trop Dis. .

Erratum in

Abstract

Background: In tropical areas, a major concern regarding snakebites treatment effectiveness relates to the failure in liquid antivenom (AV) distribution due to the lack of an adequate cold chain in remote areas. To minimize this problem, freeze-drying has been suggested to improve AV stability.

Methods and findings: This study compares the safety and efficacy of a freeze-dried trivalent antivenom (FDTAV) and the standard liquid AV provided by the Brazilian Ministry of Health (SLAV) to treat Bothrops, Lachesis and Crotalus snakebites. This was a prospective, randomized, open, phase IIb trial, carried out from June 2005 to May 2008 in the Brazilian Amazon. Primary efficacy endpoints were the suppression of clinical manifestations and return of hemostasis and renal function markers to normal ranges within the first 24 hours of follow-up. Primary safety endpoint was the presence of early adverse reactions (EAR) in the first 24 hours after treatment. FDTAV thermal stability was determined by estimating AV potency over one year at 56°C. Of the patients recruited, 65 and 51 were assigned to FDTAV and SLAV groups, respectively. Only mild EARs were reported, and they were not different between groups. There were no differences in fibrinogen (p = 0.911) and clotting time (p = 0.982) recovery between FDTAV and SLAV treated groups for Bothrops snakebites. For Lachesis and Crotalus snakebites, coagulation parameters and creatine phosphokinase presented normal values 24 hours after AV therapy for both antivenoms.

Conclusions/significance: Since promising results were observed for efficacy, safety and thermal stability, our results indicate that FDTAV is suitable for a larger phase III trial.

Trial registration: ISRCTNregistry: ISRCTN12845255; DOI: 10.1186/ISRCTN12845255 (http://www.isrctn.com/ISRCTN12845255).

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Flow chart of inclusion in the clinical trial.
Fig 2
Fig 2. Survival analysis of the primary efficacy endpoint.
Time until fibrinogen (Part A) and clotting time (Part B) reaching normal values over follow-up of patients bitten by Bothrops snakes presented no significant difference between freeze-dried trivalent antivenom (FDTAV) and Ministry of Health standard liquid antivenoms (SLAVs) treated groups.
Fig 3
Fig 3. Primary efficacy endpoint analysis in Bothrops snakebites.
Clotting time, fibrinogen and INR levels 24 hours after AV therapy in freeze-dried trivalent antivenom (FDTAV) and Ministry of Health standard liquid antivenoms (SLAVs) treated groups.
Fig 4
Fig 4. Thermostability evaluations of the freeze-dried trivalent antivenom (FDTAV) at 56°C over one year.
Antivenom potency for neutralizing Bothrops, Lachesis and Crotalus activities showed no significant decrease compared to baseline over one year of thermostability evaluations at 56°C.

References

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