BMC Cancer. 2013 Jun 13;13:284. doi: 10.1186/1471-2407-13-284.
Low-molecular-weight heparin (LMWH) is recommended and commonly used for extended treatment of cancer-associated thrombosis (CAT), but its superiority over warfarin has been demonstrated in only one randomised study. We report here the rationale, design and a priori analysis plans of Comparison of Acute Treatments in Cancer Haemostasis (CATCH; NCT01130025), a multinational, Phase III, open-label, randomised controlled trial comparing tinzaparin with warfarin for extended treatment of CAT.
METHODS/DESIGN: The primary objective is to assess the efficacy of tinzaparin in preventing recurrent venous thromboembolism (VTE) in patients with active cancer and acute, symptomatic proximal deep vein thrombosis and/or pulmonary embolism. The secondary objectives are to determine: safety of tinzaparin given over 6 months; clinical and laboratory markers for recurrent VTE and/or major bleeding; 6-month overall mortality; incidence and severity of post-thrombotic syndrome; patient-reported quality of life; and healthcare resource utilisation. Nine hundred patients are randomised to receive tinzaparin 175 IU/kg once daily for 6 months or initial tinzaparin 175 IU/kg once daily for 5-10 days and dose-adjusted warfarin (target INR 2.0-3.0) for 6 months. The primary composite outcome is time to recurrent VTE, including incidental VTE and fatal pulmonary embolism. All patients are followed up to 6 months or death, whichever comes sooner. Blinded adjudication will be performed for all reported VTE, bleeding events and causes of death. Efficacy will be analysed using centrally adjudicated results of all patients according to intention-to-treat analysis. An independent Data Safety Monitoring Board is reviewing data at regular intervals and an interim analysis is planned after 450 patients have completed the study.
The results will add significantly to the knowledge of the efficacy, safety and cost effectiveness of tinzaparin in the prevention of recurrent VTE in patients with cancer and thrombosis. Prospective data will emerge on the clinical significance of incidental VTE and risk stratification in patients with CAT. Results on post-thrombotic syndrome, quality of life and healthcare resource utilisation will inform decision makers on how to secure better patient care. If tinzaparin is shown to be more effective than warfarin, CATCH will provide valuable confirmatory data to support the use of the LMWH tinzaparin for extended treatment of CAT.
低分子肝素（LMWH）被推荐并常用于癌症相关血栓形成（CAT）的延长治疗，但仅在一项随机研究中证明其优于华法林。我们在此报告比较急性癌症止血治疗（CATCH；NCT01130025）的原理、设计和预先分析计划，这是一项多中心、III 期、开放性、随机对照试验，比较替扎肝素与华法林在 CAT 的延长治疗中的疗效。
方法/设计：主要目的是评估替扎肝素预防活动性癌症伴急性、有症状的近端深静脉血栓形成和/或肺栓塞患者复发性静脉血栓栓塞（VTE）的疗效。次要目标是确定：替扎肝素治疗 6 个月的安全性；复发性 VTE 和/或大出血的临床和实验室标志物；6 个月总死亡率；血栓后综合征的发生率和严重程度；患者报告的生活质量；以及医疗保健资源的利用。900 名患者被随机分配接受替扎肝素 175 IU/kg 每日一次治疗 6 个月或初始替扎肝素 175 IU/kg 每日一次治疗 5-10 天，然后调整剂量的华法林（目标 INR 2.0-3.0）治疗 6 个月。主要复合结局是复发性 VTE 的时间，包括偶发性 VTE 和致命性肺栓塞。所有患者随访至 6 个月或死亡，以先发生者为准。所有报告的 VTE、出血事件和死亡原因均将进行盲法裁决。将根据意向治疗分析对所有患者进行中心裁决的结果进行疗效分析。一个独立的数据安全监测委员会定期审查数据，并计划在 450 名患者完成研究后进行中期分析。
研究结果将极大地增加我们对替扎肝素预防癌症和血栓形成患者复发性 VTE 的疗效、安全性和成本效益的认识。前瞻性数据将揭示 CAT 患者偶发性 VTE 和风险分层的临床意义。关于血栓后综合征、生活质量和医疗保健资源利用的结果将为决策者提供有关如何确保更好的患者护理的信息。如果替扎肝素被证明比华法林更有效，CATCH 将提供有价值的确证数据，以支持使用 LMWH 替扎肝素治疗 CAT。
