期刊
SHOCK
卷 47, 期 5, 页码 567-573出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/SHK.0000000000000788
关键词
Clinical trial; outcomes; resuscitation; transfusion; trauma
资金
- US National Heart, Lung, and Blood Institute [U01HL077863]
- US Department of Defense
- Defence Research and Development Canada
- Canadian Institutes of Health Research (CIHR)-Institute of Circulatory and Respiratory Health [CRR-120612]
Background: Choosing the appropriate endpoint for a trauma hemorrhage control trial can determine the likelihood of its success. Recent Phase 3 trials and observational studies have used 24-h and/or 30-day all-cause mortality as the primary endpoint and some have not used exception from informed consent (EFIC), resulting in multiple failed trials. Five recent high-quality prospective studies among 4,064 hemorrhaging trauma patients provide new evidence to support earlier primary endpoints. Methods: The goal of this project was to determine the optimal endpoint for hemorrhage control trials using existing literature and new analyses of previously published data. Results: Recent studies among bleeding trauma patients show that hemorrhagic deaths occur rapidly, at a high rate, and in a consistent pattern. Early preventable deaths among trauma patients are largely due to hemorrhage and the median time to hemorrhagic death from admission is 2.0 to 2.6 h. Approximately 85% of hemorrhagic deaths occur within 6 h. The hourly mortality rate due to traumatic injury decreases rapidly after enrollment from 4.6% per hour at 1 hour postenrollment to 1% per hour at 6 h to <0.1% per hour by 9 h and thereafter. Early primary endpoints (within 6 h) have critically important benefits for hemorrhage control trials, including being congruent with the median time to hemorrhagic death, biologic plausibility, and enabling the use of all-cause mortality, which is definitive and objective. Conclusions: Primary endpoints should be congruent with the timing of the disease process. Therefore, if a resuscitation/hemorrhage control intervention is under study, a primary endpoint of all-causemortality evaluated within the first 6 h is appropriate. Before choosing the timing of the primary endpoint for a large multicenter trial, we recommend performing a Phase 2 trial under EFIC to better understand the effects of the hemorrhage control intervention and distribution of time to death. When early primary endpoints are used, patients should be monitored for multiple subsequent secondary safety endpoints, including 24 h and 30-day all-cause mortality as well as the customary safety endpoints.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据