Department of Medicine, McMaster University, Hamilton, Ontario, Canada L8N 3Z5.
J Crit Care. 2011 Apr;26(2):223.e1-9. doi: 10.1016/j.jcrc.2011.02.010.
This article reports the preparatory studies as well as the design, implementation, and a priori analysis plans of PROphylaxis for ThromboEmbolism in Critical Care Trial (PROTECT) before dissemination of results. PROphylaxis for ThromboEmbolism in Critical Care Trial (NCT00182143) is a randomized, stratified, concealed international trial comparing subcutaneous injection of unfractionated heparin (UFH) 5000 IU or the low-molecular weight heparin (LMWH) dalteparin 5000 IU once daily plus once-daily placebo for the duration of the intensive care unit stay.
The objective of PROTECT is to examine, among medical-surgical critically ill patients, the effect of the LMWH vs heparin on the primary outcome of proximal leg deep vein thrombosis (DVT) and the following secondary outcomes: DVT elsewhere, pulmonary embolism, any venous thromboembolism (DVT or pulmonary embolism), the composite of venous thromboembolism or death, bleeding, and heparin-induced thrombocytopenia. Patients are followed up to death or hospital discharge. Venous thromboembolism events were included after intensive care unit discharge. All patients, families, clinicians, research personnel, and the trial biostatistician are blind to allocation.
We describe the pilot work, large trial methodology, implementation methods, and the analytic plan. Patient recruitment is complete, but 2 patients remain in the hospital. The rigorous design of PROTECT suggests that the risk of systematic error will be low. The sample size suggests that the risk of random error will be low. PROTECT will be the largest investigator-initiated peer-review funded thromboprophylaxis trial in critical care in the world.
If PROTECT shows that LMWH is more effective than UFH, this trial will change practice in that LMWH may be the anticoagulant thromboprophylaxis of choice for this population. If the results show that UFH is as effective or more effective than LMWH, intensivists in many parts of the world may continue to use UFH, whereas those currently using LMWH may reconsider and change to use UFH. Unfavorable consequences such as major bleeding, ease of use, and the costs of complications will also factor into such decisions.
本文报告了 PROphylaxis for ThromboEmbolism in Critical Care Trial（PROTECT）在公布研究结果之前的预备研究以及设计、实施和预先分析计划。PROphylaxis for ThromboEmbolism in Critical Care Trial（NCT00182143）是一项随机、分层、隐蔽的国际试验，比较了皮下注射未分馏肝素（UFH）5000IU 或低分子肝素（LMWH）达肝素 5000IU 每日一次加每日一次安慰剂，持续整个重症监护病房住院时间。
PROTECT 的目的是在外科重症监护患者中，检查 LMWH 与肝素对主要结局近端腿部深静脉血栓形成（DVT）的影响，以及以下次要结局：其他部位 DVT、肺栓塞、任何静脉血栓栓塞症（DVT 或肺栓塞）、静脉血栓栓塞症或死亡的复合、出血和肝素诱导的血小板减少症。患者随访至死亡或出院。静脉血栓栓塞事件包括重症监护病房出院后。所有患者、家属、临床医生、研究人员和试验生物统计学家均对分配情况不知情。
我们描述了试验的预试验工作、大型试验方法学、实施方法和分析计划。患者招募已完成，但仍有 2 名患者住院。PROTECT 的严格设计表明系统误差的风险较低。样本量表明随机误差的风险较低。PROTECT 将成为全球最大的由研究者发起的同行评审资助的重症监护抗血栓形成试验。
如果 PROTECT 表明 LMWH 比 UFH 更有效，该试验将改变实践，即 LMWH 可能成为该人群的抗凝血栓形成预防的首选药物。如果结果表明 UFH 与 LMWH 一样有效或更有效，那么世界上许多地区的重症监护医生可能会继续使用 UFH，而那些目前使用 LMWH 的医生可能会重新考虑并改用 UFH。大出血等不利后果、使用便利性和并发症的成本也将成为这些决策的因素。
