Very early administration of progesterone for acute traumatic brain injury.
Very early administration of progesterone for acute traumatic brain injury.
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DOI：
10.1056/nejmoa1404304
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发表时间：
2014-12-25
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影响因子：
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通讯作者：
NETT Investigators
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作者：
Wright DW;Yeatts SD;Silbergleit R;Palesch YY;Hertzberg VS;Frankel M;Goldstein FC;Caveney AF;Howlett-Smith H;Bengelink EM;Manley GT;Merck LH;Janis LS;Barsan WG;NETT Investigators
创伤性脑损伤（TBI）是世界范围内死亡和残疾的主要原因。在多个实验模型和两个涉及TBI患者的早期试验中，已显示预后改善神经功能结局。我们进行了一项双盲、多中心的临床试验，（格拉斯哥昏迷量表评分为4至12分，在3至15分的量表上，较低的评分表明意识水平较低）被随机分配到静脉注射黄体酮或安慰剂组，在损伤后4小时内开始研究治疗，并施用总共96小时。疗效定义为损伤后6个月时使用扩展格拉斯哥结局量表评分的分层二分法确定的结局良好的患者比例增加10个百分点。次要结局包括死亡率和残疾评定量表评分。在计划的1140例患者样本中，共有882例患者在试验因主要结局无效而停止前接受了随机化。研究组在基线特征方面相似;患者的中位年龄为35岁，73.7%为男性，15.2%为黑人，平均损伤严重程度评分为24.4（评分范围为0 - 75，评分越高表示严重程度越高）。最常见的伤害机制是机动车事故。孕酮组和安慰剂组在良好结局的患者比例方面没有显著差异（孕酮的相对获益为0.95; 95%置信区间[CI]为0.85 - 1.06; P = 0.35）。静脉炎或血栓性静脉炎在黄体酮组比安慰剂组更常见（相对危险度，3.03; CI，1.96 - 4.66）。其他预先规定的安全性结局无显著差异。这项临床试验没有显示孕酮在改善急性TBI患者预后方面优于安慰剂。（由国家神经疾病和中风研究所和其他机构资助; WCTIII ClinicalTrials.gov编号，NCT 00822900。
Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Progesterone has been shown to improve neurologic outcome in multiple experimental models and two early-phase trials involving patients with TBI. We conducted a double-blind, multicenter clinical trial in which patients with severe, moderate-to-severe, or moderate acute TBI (Glasgow Coma Scale score of 4 to 12, on a scale from 3 to 15, with lower scores indicating a lower level of consciousness) were randomly assigned to intravenous progesterone or placebo, with the study treatment initiated within 4 hours after injury and administered for a total of 96 hours. Efficacy was defined as an increase of 10 percentage points in the proportion of patients with a favorable outcome, as determined with the use of the stratified dichotomy of the Extended Glasgow Outcome Scale score at 6 months after injury. Secondary outcomes included mortality and the Disability Rating Scale score. A total of 882 of the planned sample of 1140 patients underwent randomization before the trial was stopped for futility with respect to the primary outcome. The study groups were similar with regard to baseline characteristics; the median age of the patients was 35 years, 73.7% were men, 15.2% were black, and the mean Injury Severity Score was 24.4 (on a scale from 0 to 75, with higher scores indicating greater severity). The most frequent mechanism of injury was a motor vehicle accident. There was no significant difference between the progesterone group and the placebo group in the proportion of patients with a favorable outcome (relative benefit of progesterone, 0.95; 95% confidence interval [CI], 0.85 to 1.06; P = 0.35). Phlebitis or thrombophlebitis was more frequent in the progesterone group than in the placebo group (relative risk, 3.03; CI, 1.96 to 4.66). There were no significant differences in the other prespecified safety outcomes. This clinical trial did not show a benefit of progesterone over placebo in the improvement of outcomes in patients with acute TBI. (Funded by the National Institute of Neurological Disorders and Stroke and others; PROTECT III ClinicalTrials.gov number, NCT00822900.)