Objective 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. Design Multicentre, open label, randomised controlled trial. Settings 12 hospitals in Quebec and Ontario, Canada, between 25 October 2011 and 31 December 2020. Participants 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. Interventions 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. Main outcome measures 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. Results 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). Conclusions 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. Trial registration ClinicalTrials.gov [NCT01455831][1]. De-anonymised patient level data and the full dataset with low risk of identification are available on reasonable request from the corresponding author after approval by the trial steering committee and Ottawa Hospital Research Institute. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01455831&atom=%2Fbmj%2F378%2Fbmj-2022-071375.atom

中文翻译：

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延长低分子肝素围手术期血栓预防对结直肠癌手术切除后无病生存期的有效性和安全性（PERIOP-01）：多中心、开放标签、随机对照试验

目的在评估结直肠癌切除患者的无病生存期时，确定低分子肝素延长围手术期血栓预防的有效性和安全性。设计多中心、开放标签、随机对照试验。设置 2011 年 10 月 25 日至 2020 年 12 月 31 日期间，加拿大魁北克和安大略省的 12 家医院。参与者 614 名成年人（年龄≥18 岁）符合病理证实的结肠或直肠浸润性腺癌，无转移性疾病证据，血红蛋白浓度≥8 g/dL，并计划进行手术切除。干预 随机分配到使用每日皮下注射 4500 IU 的 tinzaparin 延长持续时间的血栓预防，从决定手术开始，术后持续 56 天，与仅住院患者术后血栓预防相比。主要结果测量 主要结果是三年无病生存，定义为无局部复发、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期。在意向治疗人群中进行了分析。结果 中期分析无效后，试验提前停止招募。主要结局发生在延长疗程组 307 名患者中的 235 名（77%）和院内血栓预防组 307 名患者中的 243 名（79%）（风险比 1.1，95% 置信区间 0.90 至 1.33；P= 0.4)。延长疗程组有 5 例患者（2%）发生术后静脉血栓栓塞，院内血栓预防组有 4 例患者（1%）发生术后静脉血栓栓塞（P=0.8）。术后第一周有1人（<1%）报告了与大手术相关的出血，延长病程有1人（<1%），院内血栓预防组有6人（2%）（P=0.1）。延长疗程组 272 名（89%）患者和住院血栓预防组 280 名（91%）患者的 5 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)。结论 与单独住院术后血栓预防相比，延长亭扎肝素围手术期抗凝治疗的时间并不能提高接受手术切除的结直肠癌患者的无病生存期或总生存期。静脉血栓栓塞和术后大出血的发生率较低且组间相似。试验注册 ClinicalTrials.gov [NCT01455831][1]。经试验指导委员会和渥太华医院研究所批准后，可根据通讯作者的合理要求提供去匿名患者水平数据和低识别风险的完整数据集。[1]：/lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01455831&atom=%2Fbmj%2F378%2Fbmj-2022-071375.atom 静脉血栓栓塞和术后大出血的发生率较低且组间相似。试验注册 ClinicalTrials.gov [NCT01455831][1]。经试验指导委员会和渥太华医院研究所批准后，可根据通讯作者的合理要求提供去匿名患者水平数据和低识别风险的完整数据集。[1]：/lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01455831&atom=%2Fbmj%2F378%2Fbmj-2022-071375.atom 静脉血栓栓塞和术后大出血的发生率较低且组间相似。试验注册 ClinicalTrials.gov [NCT01455831][1]。经试验指导委员会和渥太华医院研究所批准后，可根据通讯作者的合理要求提供去匿名患者水平数据和低识别风险的完整数据集。[1]：/lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01455831&atom=%2Fbmj%2F378%2Fbmj-2022-071375.atom 经试验指导委员会和渥太华医院研究所批准后，可根据通讯作者的合理要求提供去匿名患者水平数据和低识别风险的完整数据集。[1]：/lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01455831&atom=%2Fbmj%2F378%2Fbmj-2022-071375.atom 经试验指导委员会和渥太华医院研究所批准后，可根据通讯作者的合理要求提供去匿名患者水平数据和低识别风险的完整数据集。[1]：/lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01455831&atom=%2Fbmj%2F378%2Fbmj-2022-071375.atom