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Snakebite clinical trials -

Michael Abouyannis, Dinesh Aggarwal, David G Lalloo, Nicholas R Casewell, Mainga Hamaluba, Hanif Esmail.

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Clinical outcomes and outcome measurement tools reported in randomised controlled trials of treatment for snakebite envenoming: A systematic review Background Snakebite is a priority neglected tropical disease and causes a range of complications that vary depending on the snake species.

Contributors Michael Abouyannis, Dinesh Aggarwal, David G Lalloo, Nicholas R Casewell, Mainga Hamaluba, Hanif Esmail Publication Journal: PLoS Negl Trop Dis Volume: 15 Issue: 8 Pages: - Year: DOI: Target Population Age Range: 0 - Sex: Either Nature of Intervention: Any.

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Comparison of two Anti Snake Venom protocols in hemotoxic snake bite: A randomized trial. Journal of Forensic and Legal Medicine. Krishnan B. Clinical effects of N-acetylcysteine on acute kidney injury and other serious morbidities in childrenwith snake envenomation: A randomized double blind placebo controlled study.

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Clinical trial of two antivenoms for the treatment of Bothrops and Lachesis bites in the north eastern Amazon region of Brazil. Otero-Patiño R, Segura A, Herrera M, Angulo Y, León G, Gutiérrez JM, et al. Cardoso JL, Fan HW, França FO, Jorge MT, Leite RP, Nishioka SA, et al.

Randomized comparative trial of three antivenoms in the treatment of envenoming by lance-headed vipers Bothrops jararaca in São Paulo, Brazil.

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Qureshi H, Alam SE, Mustufa MA, Nomani NK, Asnani JL, Sharif M. Comparative cost and efficacy trial of Pakistani versus Indian anti snake venom. The information on the efficacy of anti-inflammatory drugs, 37 PBMT, 22 and toxin inhibitors 40 in SBEs is restricted to the results of preclinical studies.

PBMT has shown efficacy in reducing myonecrosis, inflammatory response, pain, and edema in preclinical studies 22 but, to our knowledge, has never been tested on patients with SBE. In recent years, the capacity of PBMT to modulate the inflammatory response, including edema and pain, as well as to enhance the healing process has led to an increase in its use in several pathological conditions.

In addition, the literature shows that PBMT is a noninvasive, safe, and painless treatment. In this study, the feasibility, safety, and efficacy of the LLLT was demonstrated in B atrox SBEs in a double-blind, randomized clinical feasibility trial.

A major challenge of the study was the substantial number of patients who were ineligible for recruitment, which meant that the study took longer than expected.

However, the careful selection of patients ensured homogeneity between the groups. In Bothrops SBEs, pain is usually the first sign to appear and alerts the patient to the situation. This manifestation is present in practically all patients. Our results corroborate those of previous studies carried out in animals.

Edema is also a frequent clinical manifestation in Bothrops envenomations. There is evidence that LLLT improves blood flow, which increases the reabsorption of edema and the clearance of catabolites derived from the inflammatory process, 24 as well as providing an efficient supply of nutritional and defensive elements to the injured region.

In Bothrops venoms, most subtypes of phospholipase A 2 PLA 2 exert myotoxic effects that may lead to necrosis and permanent tissue damage. The mechanism has not been fully elucidated, but previous studies have suggested that muscle damage was secondary to tissue ischemia associated with bleeding.

Nonetheless, there was an increase in the comparator group, which indicates a worsening of local tissue injury. Our findings agree with previous reports regarding animals experimentally subjected to Bothrops moojeni and Bothrops asper venoms, in which PBMT was effective in reducing myonecrosis when observed by measuring plasma creatine kinase levels and through histological analysis.

Technological evolution has facilitated clinical evaluation of snakebites through the use of thermography equipment that, in this study, allowed the precise delimitation of the area of inflammation for the application of LLLT, instead of using only measurement with a tape measure.

Thus, the combination of these tools, thermography and 8-tip LLLT, benefited the evaluation and conclusion of the intervention by making it more efficient.

This study provides promising evidence for the use of LLLT in reducing the local complications of Bothrops envenomation, besides exerting a local analgesic effect.

The results also indicated that LLLT was able to reduce myonecrosis, consequently improving the healing process in patients bitten by Bothrops , and thus improving their quality of life.

In addition to the demonstrated efficacy, the procedure was safe. This study had some limitations. This was a small, single-site clinical trial. Even though the pathophysiology and clinical characteristics of SBEs caused by different Bothrops species are similar, the fact that this study was conducted at a single center in the Amazon, where cases are due almost exclusively to B atrox , limits the generalizability of the results to other endemic sites.

We suggest that larger studies be conducted to confirm our findings and to estimate the efficacy of LLLT to prevent less frequent patient-centered outcomes, especially long-term disabilities.

In our study, we had resources such as thermography to limit the LLLT application area, and an 8-point laser device, which made the application faster. These resources make treatment more expensive and may limit its use in the field. In this randomized clinical trial, PBMT was feasible and was effective in reducing myonecrosis and local inflammatory effects, namely pain and edema caused by B atrox envenomations.

This clinical trial will help to prepare the ground for a larger, more definitive trial to improve treatment for this neglected public health problem.

Published Online: December 4, Correction: This article was corrected on January 16, , to correct the mean SD extent of edema at 48 hours for the intervention group to Open Access: This is an open access article distributed under the terms of the CC-BY License.

JAMA Internal Medicine. Corresponding Author: Jacqueline de Almeida Gonçalves Sachett, PhD, Av Pedro Teixeira, 25, Dom Pedro, Manaus, AM, Brazil jac. sachett gmail.

Author Contributions: Dr J. Sachett had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: J. Sachett, Carvalho, Farias, Sampaio, Balieiro, Zamuner, Cabral, Monteiro. Drafting of the manuscript: J.

Sachett, Carvalho, Souza, Melo, Farias, Macedo, Sartim, Caggy, Rodrigues, Araújo, Ribeiro, Reis, A. Sachett, Balieiro, Zamuner, Vissoci, Cabral, Monteiro. Critical review of the manuscript for important intellectual content: J. Sachett, Carvalho, Farias, Sartim, Silva, Sampaio, Zamuner, Vissoci, Cabral, Monteiro.

Statistical analysis: J. Sachett, Carvalho, Farias, Sartim, A. Sachett, Sampaio, Balieiro, Zamuner, Vissoci, Monteiro. Administrative, technical, or material support: J. Sachett, Carvalho, Souza, Melo, Farias, Macedo, Caggy, Araújo, Ribeiro, Reis, Silva, A. Sachett, Zamuner, Cabral, Monteiro.

Supervision: J. Sachett, Carvalho, Sartim, Rodrigues, Sampaio, Cabral, Monteiro. Conflict of Interest Disclosures: None reported.

Data Sharing Statement: See Supplement 3. Additional Contributions: We thank all patients who agreed to participate in this study. We appreciate the support of the medical and nursing staff of the Fundação de Medicina Tropical Doutor Heitor Vieira Dourado FMT-HVD.

We benefited by the important contribution from the clinical laboratory of FMT-HVD, namely that of Yonne Francis Chehuan Melo, MSc.

She did not receive compensation for this contribution. full text icon Full Text. Download PDF Comment.

Top of Article Key Points Abstract Introduction Methods Results Discussion Conclusions Article Information References. Visual Abstract. Photobiomodulation Therapy to Treat Snakebites Caused by Bothrops atrox.

View Large Download. Figure 1. Flowchart for the Inclusion of Study Participants. Figure 2. Kaplan-Meier Survival Analysis Comparing Changes Over Time Between the Low-Level Laser Therapy LLLT and the Comparison Group. Table 1. Epidemiological, Clinical, and Laboratory Characteristics of the Study Participants.

Table 2. Efficacy Outcomes Results. Supplement 1. Trial Protocol. Supplement 2. eFigure 1 eFigure 2. Supplement 3. Data Sharing Statement. Gutiérrez JM. Snakebite envenoming from an Ecohealth perspective.

doi: Harrison RA, Hargreaves A, Wagstaff SC, Faragher B, Lalloo DG. Snake envenoming: a disease of poverty. Chaves LF, Chuang TW, Sasa M, Gutiérrez JM. Snakebites are associated with poverty, weather fluctuations, and El Niño.

Gutiérrez JM, Calvete JJ, Habib AG, Harrison RA, Williams DJ, Warrell DA. Snakebite envenoming. Chippaux JP. Incidence and mortality due to snakebite in the Americas. da Silva AM, Colombini M, Moura-da-Silva AM, de Souza RM, Monteiro WM, Bernarde PS.

Ethno-knowledge and attitudes regarding snakebites in the Alto Juruá region, Western Brazilian Amazonia. Kasturiratne A, Pathmeswaran A, Wickremasinghe AR, et al. The socio-economic burden of snakebite in Sri Lanka. Feitosa EL, Sampaio VS, Salinas JL, et al.

Older age and time to medical assistance are associated with severity and mortality of snakebites in the Brazilian Amazon: a case-control study. Hui Wen F, Monteiro WM, Moura da Silva AM, et al. Snakebites and scorpion stings in the Brazilian Amazon: identifying research priorities for a largely neglected problem.

Monteiro WM, Contreras-Bernal JC, Bisneto PF, et al. Bothrops atrox , the most important snake involved in human envenomings in the amazon: how venomics contributes to the knowledge of snake biology and clinical toxinology. Valente RH, Guimarães PR, Junqueira M, et al. Bothrops insularis venomics: a proteomic analysis supported by transcriptomic-generated sequence data.

Sousa LF, Portes-Junior JA, Nicolau CA, et al. Functional proteomic analyses of Bothrops atrox venom reveals phenotypes associated with habitat variation in the Amazon. Amorim FG, Costa TR, Baiwir D, De Pauw E, Quinton L, Sampaio SV. Proteopeptidomic, functional and immunoreactivity characterization of Bothrops moojeni snake venom: influence of snake gender on venom composition.

Almeida MT, Freitas-de-Sousa LA, Colombini M, et al. Inflammatory reaction induced by two metalloproteinases isolated from Bothrops atrox venom and by fragments generated from the hydrolysis of basement membrane components. Gimenes SNC, Sachett JAG, Colombini M, et al.

Observation of Bothrops atrox snake envenoming blister formation from five patients: pathophysiological insights. Sachett JAG, Val FF, Alcântara JA, et al. Bothrops atrox snakebite: how a bad decision may lead to a chronic disability: a case report. Gerardo CJC, Vissoci JRN, Evans CS, Simel DL, Lavonas EJ.

Does this patient have a severe snake envenomation? Ministério da Saúde. Guia de vigilância em saúde. Accessed October 24, Furtado MdeF, Cardoso ST, Soares OE, et al.

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Segura A, Castillo MC, Núñez V, et al. Preclinical assessment of the neutralizing capacity of antivenoms produced in six Latin American countries against medically-relevant Bothrops snake venoms. Silva LMG, Zamuner LF, David AC, Dos Santos SA, de Carvalho PTC, Zamuner SR.

Photobiomodulation therapy on Bothrops snake venom-induced local pathological effects: a systematic review. Barbosa AM, Villaverde AB, Guimarães-Souza L, Ribeiro W, Cogo JC, Zamuner SR. Effect of low-level laser therapy in the inflammatory response induced by Bothrops jararacussu snake venom.

Dourado DM, Fávero S, Baranauskas V, da Cruz-Höfling MA.

This guideline should not be used outside Tirals due to regional differences Beta-alanine and muscular fatigue Snake species. For 24 Snakebite clinical trials Snkebite, contact Snakebihe Poisons Information Centre Snkebite 11 Snake bite is uncommon in Victoria and envenomation systemic poisoning from the bite is rare. The bite site may be evidenced by fang marks, one or multiple scratches. The bite site may be painful, swollen or bruised, but usually is not for snakes in Victoria. Snakebite clinical trials Snakebite is an clinicwl, unmet global trialls need cliincal significant morbidity and mortality worldwide. Varespladib is Post-game muscle recovery potent inhibitor Snakebite clinical trials venom Snakebite clinical trials phospholipase A truals sPLA 2 that can clinicall administered orally ckinical its prodrug, varespladib-methyl. Extensive cliniczl data support clinical evaluation of Snakebite clinical trials Wearable glucose monitoring a treatment for snakebite envenoming SBE. The protocol reported here was designed to evaluate varespladib-methyl for SBE from any snake species in multiple geographies. Methods and analysis: BRAVO Broad-spectrum Rapid Antidote: Varespladib Oral for snakebite is a multicenter, randomized, double-blind, placebo-controlled, phase 2 study to evaluate the safety, tolerability, and efficacy of oral varespladib-methyl plus standard of care SoC vs. SoC plus placebo in patients presenting with acute SBE by any venomous snake species. Male and female patients 5 years of age and older who meet eligibility criteria will be randomly assigned to varespladib-methyl or placebo.

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Case Discussion -- Snake bite