Department of Surgery, University of Ottawa, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
Department of Surgery, London Health Sciences Centre, London, ON, Canada.
BMJ. 2022 Sep 13;378:e071375. doi: 10.1136/bmj-2022-071375.
To determine the efficacy and safety of extended duration perioperative thromboprophylaxis by low molecular weight heparin when assessing disease-free survival in patients undergoing resection for colorectal cancer.
Multicentre, open label, randomised controlled trial.
12 hospitals in Quebec and Ontario, Canada, between 25 October 2011 and 31 December 2020.
614 adults (age ≥18 years) were eligible with pathologically confirmed invasive adenocarcinoma of the colon or rectum, no evidence of metastatic disease, a haemoglobin concentration of ≥8 g/dL, and were scheduled to undergo surgical resection.
Random assignment to extended duration thromboprophylaxis using daily subcutaneous tinzaparin at 4500 IU, beginning at decision to operate and continuing for 56 days postoperatively, compared with in-patient postoperative thromboprophylaxis only.
Primary outcome was disease-free survival at three years, defined as survival without locoregional recurrence, distant metastases, second primary (same cancer), second primary (other cancer), or death. Secondary outcomes included venous thromboembolism, postoperative major bleeding complications, and five year overall survival. Analyses were done in the intention-to-treat population.
The trial stopped recruitment prematurely after the interim analysis for futility. The primary outcome occurred in 235 (77%) of 307 patients in the extended duration group and in 243 (79%) of 307 patients in the in-hospital thromboprophylaxis group (hazard ratio 1.1, 95% confidence interval 0.90 to 1.33; P=0.4). Postoperative venous thromboembolism occurred in five patients (2%) in the extended duration group and in four patients (1%) in the in-hospital thromboprophylaxis group (P=0.8). Major surgery related bleeding in the first postoperative week was reported in one person (<1%) in the extended duration and in six people (2%) in the in-hospital thromboprophylaxis group (P=0.1). No difference was noted for overall survival at five years in 272 (89%) patients in the extended duration group and 280 (91%) patients in the in-hospital thromboprophylaxis group (hazard ratio 1.12; 95% confidence interval 0.72 to 1.76; P=0.1).
Extended duration to perioperative anticoagulation with tinzaparin did not improve disease-free survival or overall survival in patients with colorectal cancer undergoing surgical resection compared with in-patient postoperative thromboprophylaxis alone. The incidences of venous thromboembolism and postoperative major bleeding were low and similar between groups.
ClinicalTrials.gov NCT01455831.
评估结直肠癌患者无病生存情况时，确定低分子肝素围手术期延长持续时间预防性抗凝的疗效和安全性。
多中心、开放标签、随机对照试验。
2011 年 10 月 25 日至 2020 年 12 月 31 日期间，加拿大魁北克省和安大略省的 12 家医院。
614 名成年人（年龄≥18 岁）符合条件，包括经病理证实的结肠或直肠侵袭性腺癌、无转移性疾病证据、血红蛋白浓度≥8g/dL，并计划接受手术切除。
随机分配至每日皮下给予达肝素钠 4500IU 的延长持续时间血栓预防治疗，从决定手术开始，并持续术后 56 天，与仅住院术后血栓预防治疗相比。
主要结局为三年无病生存，定义为无局部区域复发、远处转移、第二原发（相同癌症）、第二原发（其他癌症）或死亡的生存。次要结局包括静脉血栓栓塞、术后大出血并发症和五年总生存。分析采用意向治疗人群。
中期分析结果显示无效后，试验提前停止招募。在延长持续时间组的 307 名患者中有 235 名（77%）和在住院期间血栓预防组的 307 名患者中有 243 名（79%）发生了主要结局（风险比 1.1，95%置信区间 0.90 至 1.33；P=0.4）。在延长持续时间组中有 5 名患者（2%）和在住院期间血栓预防组中有 4 名患者（1%）发生术后静脉血栓栓塞（P=0.8）。在术后第一周内报告了 1 名（<1%）延长持续时间组和 6 名（2%）住院期间血栓预防组患者的主要手术相关出血（P=0.1）。在延长持续时间组的 272 名患者（89%）和住院期间血栓预防组的 280 名患者（91%）中，五年总生存率无差异（风险比 1.12；95%置信区间 0.72 至 1.76；P=0.1）。
与单独住院术后血栓预防相比，用达肝素钠对结直肠癌患者进行围手术期抗凝的延长持续时间并未改善无病生存或总生存情况。两组静脉血栓栓塞和术后大出血的发生率均较低且相似。
ClinicalTrials.gov NCT01455831。
