Alok A. Khorana , Charles W. Francis , Nicole M. Kuderer , Marc Carrier , Thomas L. Ortel , Ted Wun , Deborah Rubens , Susan Hobbs , Renuka Iyer , Derick Peterson , Andrea Baran , Katherine Kaproth-Joslin , Gary H. Lyman
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Subjects were screened with lower extremity ultrasounds every 4<!--> <!-->weeks on study and with chest CT at 12<!--> <!-->weeks. The primary efficacy endpoint was all VTE over 12<!--> <!-->weeks and primary safety endpoint was clinically relevant bleeding events over 13<!--> <!-->weeks. The study was terminated early due to low accrual.</p></div><div><h3>Results</h3><p>Of 117 enrolled patients, 10 (8.5%) had VTE on baseline screening and were not randomized. Of 98 randomized patients, VTE occurred in 12% (N<!--> <!-->=<!--> <!-->6/50) of patients on dalteparin and 21% (N<!--> <!-->=<!--> <!-->10/48) on observation (hazard ratio, HR 0.69, 95% CI 0.23–1.89). Major bleeding was similar (N<!--> <!-->=<!--> <!-->1) in each arm but clinically relevant bleeding was higher in dalteparin arm (N<!--> <!-->=<!--> <!-->7 versus 1 on observation) (HR<!--> <!-->=<!--> <!-->7.0, 95% CI 1.2–131.6). 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引用次数: 112
摘要
背景:静脉血栓栓塞(VTE)高风险的动态癌症患者可以通过一个有效的风险评分(Khorana评分)来识别。我们在一项多中心随机研究中评估了门诊高危患者使用达特帕林预防血栓的益处。方法对Khorana评分≥3分的癌症患者进行静脉血栓栓塞筛查，如果阴性，随机分配至每天5000单位的达特帕林或观察12周。研究期间每4周进行一次下肢超声检查，12周进行胸部CT检查。主要疗效终点是12周内所有静脉血栓栓塞，主要安全性终点是13周内临床相关出血事件。由于低应计收益，本研究被提前终止。结果117例入组患者中，基线筛查时有静脉血栓栓塞10例(8.5%)，未随机分组。在98例随机分组的患者中，12% (N = 6/50)的患者服用达特帕林，21% (N = 10/48)的患者发生静脉血栓栓塞(风险比，HR 0.69, 95% CI 0.23-1.89)。各组大出血相似(N = 1)，但达达哌林组临床相关出血较高(N = 7比1)(HR = 7.0, 95% CI 1.2-131.6)。总体生存期没有差异。结论:在这项研究中，血栓预防与静脉血栓栓塞(VTE)风险的非显著降低和临床相关出血风险的显著增加相关。Khorana评分成功地识别了基线和治疗期间静脉血栓栓塞高发生率的患者。未来的研究应继续关注风险适应方法，以减少静脉血栓栓塞在癌症中的负担。临床试验注册。gov标识符:NCT00876915
Dalteparin thromboprophylaxis in cancer patients at high risk for venous thromboembolism: A randomized trial
Background
Ambulatory cancer patients at high-risk for venous thromboembolism (VTE) can be identified using a validated risk score (Khorana score). We evaluated the benefit of outpatient thromboprophylaxis with dalteparin in high-risk patients in a multicenter randomized study.
Methods
Cancer patients with Khorana score ≥ 3 starting a new systemic regimen were screened for VTE and if negative randomized to dalteparin 5000 units daily or observation for 12 weeks. Subjects were screened with lower extremity ultrasounds every 4 weeks on study and with chest CT at 12 weeks. The primary efficacy endpoint was all VTE over 12 weeks and primary safety endpoint was clinically relevant bleeding events over 13 weeks. The study was terminated early due to low accrual.
Results
Of 117 enrolled patients, 10 (8.5%) had VTE on baseline screening and were not randomized. Of 98 randomized patients, VTE occurred in 12% (N = 6/50) of patients on dalteparin and 21% (N = 10/48) on observation (hazard ratio, HR 0.69, 95% CI 0.23–1.89). Major bleeding was similar (N = 1) in each arm but clinically relevant bleeding was higher in dalteparin arm (N = 7 versus 1 on observation) (HR = 7.0, 95% CI 1.2–131.6). There was no difference in overall survival.
Conclusions
Thromboprophylaxis is associated with a non-significantly reduced risk of VTE and significantly increased risk of clinically relevant bleeding in this underpowered study. The Khorana score successfully identifies patients with high incidence of VTE both at baseline and during treatment. Future studies should continue to focus on risk-adapted approaches to reduce the burden of VTE in cancer.
期刊介绍：
Thrombosis Research is an international journal dedicated to the swift dissemination of new information on thrombosis, hemostasis, and vascular biology, aimed at advancing both science and clinical care. The journal publishes peer-reviewed original research, reviews, editorials, opinions, and critiques, covering both basic and clinical studies. Priority is given to research that promises novel approaches in the diagnosis, therapy, prognosis, and prevention of thrombotic and hemorrhagic diseases.
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