Safety and efficacy of artesunate treatment in severely injured patients with traumatic hemorrhage. The TOP-ART randomized clinical trial
<strong>Purpose<br></strong> This study aimed at determining whether intravenous artesunate is safe and effective in reducing multiple organ dysfunction syndrome in trauma patients with major hemorrhage. <br><strong> Methods<br></strong> TOP-ART, a randomize...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Springer Nature
2023
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| _version_ | 1797111578388070400 |
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| author | Shepherd, JM Ross, J Anton, L Rourke, C Brentnall, AR Tarning, J White, NJ Thiemermann, C Brohi, K |
| author_facet | Shepherd, JM Ross, J Anton, L Rourke, C Brentnall, AR Tarning, J White, NJ Thiemermann, C Brohi, K |
| author_sort | Shepherd, JM |
| collection | OXFORD |
| description | <strong>Purpose<br></strong>
This study aimed at determining whether intravenous artesunate is safe and effective in reducing multiple organ dysfunction syndrome in trauma patients with major hemorrhage.
<br><strong>
Methods<br></strong>
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.
<br><strong>
Results<br></strong>
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.
<br><strong>
Conclusion<br></strong>
Among critically ill trauma patients, artesunate is unlikely to improve organ dysfunction and might be associated with a higher VTE rate. |
| first_indexed | 2024-03-07T08:12:21Z |
| format | Journal article |
| id | oxford-uuid:370a47a3-92d2-4324-8f9a-db9ae1bdc958 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T08:12:21Z |
| publishDate | 2023 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:370a47a3-92d2-4324-8f9a-db9ae1bdc9582023-12-06T13:18:37ZSafety and efficacy of artesunate treatment in severely injured patients with traumatic hemorrhage. The TOP-ART randomized clinical trialJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:370a47a3-92d2-4324-8f9a-db9ae1bdc958EnglishSymplectic ElementsSpringer Nature2023Shepherd, JMRoss, JAnton, LRourke, CBrentnall, ARTarning, JWhite, NJThiemermann, CBrohi, K<strong>Purpose<br></strong> This study aimed at determining whether intravenous artesunate is safe and effective in reducing multiple organ dysfunction syndrome in trauma patients with major hemorrhage. <br><strong> Methods<br></strong> 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. <br><strong> Results<br></strong> 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. <br><strong> Conclusion<br></strong> Among critically ill trauma patients, artesunate is unlikely to improve organ dysfunction and might be associated with a higher VTE rate. |
| spellingShingle | Shepherd, JM Ross, J Anton, L Rourke, C Brentnall, AR Tarning, J White, NJ Thiemermann, C Brohi, K 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 |
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