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Safety and efficacy of artesunate treatment in severely injured patients with traumatic hemorrhage. The TOP-ART randomized clinical trial

PURPOSE: This study aimed at determining whether intravenous artesunate is safe and effective in reducing multiple organ dysfunction syndrome in trauma patients with major hemorrhage. METHODS: TOP-ART, a randomized, blinded, placebo-controlled, phase IIa trial, was conducted at a London major trauma...

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Autores principales: Shepherd, Joanna M., Ross, Jennifer, Anton, Lourdes, Rourke, Claire, Brentnall, Adam R., Tarning, Joel, White, Nicholas J., Thiemermann, Christoph, Brohi, Karim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10425486/
https://www.ncbi.nlm.nih.gov/pubmed/37470832
http://dx.doi.org/10.1007/s00134-023-07135-3
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author Shepherd, Joanna M.
Ross, Jennifer
Anton, Lourdes
Rourke, Claire
Brentnall, Adam R.
Tarning, Joel
White, Nicholas J.
Thiemermann, Christoph
Brohi, Karim
author_facet Shepherd, Joanna M.
Ross, Jennifer
Anton, Lourdes
Rourke, Claire
Brentnall, Adam R.
Tarning, Joel
White, Nicholas J.
Thiemermann, Christoph
Brohi, Karim
author_sort Shepherd, Joanna M.
collection PubMed
description PURPOSE: This study aimed at determining whether intravenous artesunate is safe and effective in reducing multiple organ dysfunction syndrome in trauma patients with major hemorrhage. METHODS: TOP-ART, a randomized, blinded, placebo-controlled, phase IIa trial, was conducted at a London major trauma center in adult trauma patients who activated the major hemorrhage protocol. Participants received artesunate or placebo (2:1 randomization ratio) as an intravenous bolus dose (2.4 mg/kg or 4.8 mg/kg) within 4 h of injury. The safety outcome was the 28-day serious adverse event (SAE) rate. The primary efficacy outcome was the 48 h sequential organ failure assessment (SOFA) score. The per-protocol recruitment target was 105 patients. RESULTS: The trial was terminated after enrolment of 90 patients because of safety concerns. Eighty-three participants received artesunate (n = 54) or placebo (n = 29) and formed the safety population and 75 met per-protocol criteria (48 artesunate, 27 placebo). Admission characteristics were similar between groups (overall 88% male, median age 29 years, median injury severity score 22), except participants who received artesunate were more shocked (median base deficit 9 vs. 4.7, p = 0.042). SAEs occurred in 17 artesunate participants (31%) vs. 5 who received placebo (17%). Venous thromboembolic events (VTE) occurred in 9 artesunate participants (17%) vs. 1 who received placebo (3%). Superiority of artesunate was not supported by the 48 h SOFA score (median 5.5 artesunate vs. 4 placebo, p = 0.303) or any of the trial’s secondary endpoints. CONCLUSION: Among critically ill trauma patients, artesunate is unlikely to improve organ dysfunction and might be associated with a higher VTE rate. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00134-023-07135-3.
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spelling pubmed-104254862023-08-16 Safety and efficacy of artesunate treatment in severely injured patients with traumatic hemorrhage. The TOP-ART randomized clinical trial Shepherd, Joanna M. Ross, Jennifer Anton, Lourdes Rourke, Claire Brentnall, Adam R. Tarning, Joel White, Nicholas J. Thiemermann, Christoph Brohi, Karim Intensive Care Med Original PURPOSE: This study aimed at determining whether intravenous artesunate is safe and effective in reducing multiple organ dysfunction syndrome in trauma patients with major hemorrhage. METHODS: TOP-ART, a randomized, blinded, placebo-controlled, phase IIa trial, was conducted at a London major trauma center in adult trauma patients who activated the major hemorrhage protocol. Participants received artesunate or placebo (2:1 randomization ratio) as an intravenous bolus dose (2.4 mg/kg or 4.8 mg/kg) within 4 h of injury. The safety outcome was the 28-day serious adverse event (SAE) rate. The primary efficacy outcome was the 48 h sequential organ failure assessment (SOFA) score. The per-protocol recruitment target was 105 patients. RESULTS: The trial was terminated after enrolment of 90 patients because of safety concerns. Eighty-three participants received artesunate (n = 54) or placebo (n = 29) and formed the safety population and 75 met per-protocol criteria (48 artesunate, 27 placebo). Admission characteristics were similar between groups (overall 88% male, median age 29 years, median injury severity score 22), except participants who received artesunate were more shocked (median base deficit 9 vs. 4.7, p = 0.042). SAEs occurred in 17 artesunate participants (31%) vs. 5 who received placebo (17%). Venous thromboembolic events (VTE) occurred in 9 artesunate participants (17%) vs. 1 who received placebo (3%). Superiority of artesunate was not supported by the 48 h SOFA score (median 5.5 artesunate vs. 4 placebo, p = 0.303) or any of the trial’s secondary endpoints. CONCLUSION: Among critically ill trauma patients, artesunate is unlikely to improve organ dysfunction and might be associated with a higher VTE rate. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00134-023-07135-3. Springer Berlin Heidelberg 2023-07-20 2023 /pmc/articles/PMC10425486/ /pubmed/37470832 http://dx.doi.org/10.1007/s00134-023-07135-3 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by-nc/4.0/Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Original
Shepherd, Joanna M.
Ross, Jennifer
Anton, Lourdes
Rourke, Claire
Brentnall, Adam R.
Tarning, Joel
White, Nicholas J.
Thiemermann, Christoph
Brohi, Karim
Safety and efficacy of artesunate treatment in severely injured patients with traumatic hemorrhage. The TOP-ART randomized clinical trial
title Safety and efficacy of artesunate treatment in severely injured patients with traumatic hemorrhage. The TOP-ART randomized clinical trial
title_full Safety and efficacy of artesunate treatment in severely injured patients with traumatic hemorrhage. The TOP-ART randomized clinical trial
title_fullStr Safety and efficacy of artesunate treatment in severely injured patients with traumatic hemorrhage. The TOP-ART randomized clinical trial
title_full_unstemmed Safety and efficacy of artesunate treatment in severely injured patients with traumatic hemorrhage. The TOP-ART randomized clinical trial
title_short Safety and efficacy of artesunate treatment in severely injured patients with traumatic hemorrhage. The TOP-ART randomized clinical trial
title_sort safety and efficacy of artesunate treatment in severely injured patients with traumatic hemorrhage. the top-art randomized clinical trial
topic Original
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10425486/
https://www.ncbi.nlm.nih.gov/pubmed/37470832
http://dx.doi.org/10.1007/s00134-023-07135-3
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