Comparison of Acute Treatments in Cancer Hemostasis - CATCH
The goal of the trial was to compare the safety and efficacy of subcutaneous tinzaparin compared with warfarin for 6 months in patients with acute symptomatic venous thromboembolism (VTE) secondary to cancer.
Contribution to the Literature: The CATCH trial shows that tinzaparin was not superior to oral warfarin for 6 months in reducing recurrent VTE or major bleeding events in patients with cancer-related acute symptomatic VTE.
Patients were randomized to receive tinzaparin (175 IU/kg) once daily for 6 months (n = 449) vs. conventional therapy with tinzaparin (175 IU/kg) once daily for 5-10 days followed by warfarin at a dose adjusted to maintain the international normalized ratio (INR) at 2-3 for 6 months (n = 451).
- Total number of enrollees: 900
- Duration of follow-up: 6 months
- Mean patient age: 59 years
- Percentage female: 59%
- Age ≥18 years
- Active cancer
- Acute symptomatic proximal deep vein thrombosis (DVT)/pulmonary embolism (PE)
ECOG (Eastern Cooperative Oncology Group) performance status 0-2
- Creatinine clearance of 20 ml/min/1.73 m2 or lower
- Any contraindication to anticoagulation
- Known hypersensitivity to study medications
- History of heparin-induced thrombocytopenia
- Therapeutic anticoagulation for more than 72 hours prior to randomization
- Therapeutic anticoagulation at the time of thrombotic event
- Life expectancy <6 months
- Women of childbearing potential or fertile men not using effective contraception
Other salient features/characteristics:
- Mean weight: 67 kg
- Glomerular filtration rate 30-59: 13%
- Primary tumor: Gynecologic: 22.5%, colorectal: 12%, upper gastrointestinal (GI): 12%, lung: 11%
- Qualifying event: DVT, 57%; DVT with incidental PE, 19%; PE, 10.5%
- Time in therapeutic range for warfarin: 47%
The primary outcome, recurrent VTE for tinzaparin vs. warfarin, was 7.2% vs. 10.5% (hazard ratio 0.65, 95% confidence interval 0.41-1.03; p = 0.07).
- Symptomatic DVT: 2.7% vs. 5.3%, p = 0.04
- Fatal PE: 3.8% vs. 3.8%, p = 0.89
- Major bleeding: 2.7% vs. 2.4%, p = 0.77
- Clinically relevant nonmajor bleeding: 10.9% vs. 15.3%, p = 0.004
The results of this trial indicate that tinzaparin is not superior to warfarin at 6 months at reducing recurrent VTE events in patients with cancer-related acute symptomatic VTE. There did appear to be a reduction in recurrent DVTs in the tinzaparine arm. Overall bleeding risk was similar, but clinically relevant nonmajor bleeding was lower with tinzaparin.
The CLOT trial had suggested that dalteparin was superior to warfarin for recurrent VTE prevention in patients with cancer-related acute VTE; low molecular weight heparins are also recommended by the current guidelines for this indication. In the current trial, tinzaparin did not achieve statistical significance, although there appeared to be a strong trend. A lower than anticipated recurrent VTE rate may explain some of this discrepancy. It is also unclear if a longer duration of treatment would have shown a greater treatment effect. It is possible that the optimal benefit with low molecular weight heparins may be in patients at a higher risk of recurrent VTEs.
Cost-effectiveness analyses are awaited. The role of novel oral anticoagulants specifically for this indication is also unclear.
Lee AY, Kamphuisen PW, Meyer G, et al., on behalf of the CATCH Investigators. Tinzaparin vs Warfarin for Treatment of Acute Venous Thromboembolism in Patients With Active Cancer: A Randomized Clinical Trial. JAMA 2015;314:677-86.
Keywords: Anticoagulants, Dalteparin, Heparin, Low-Molecular-Weight, Neoplasms, Pulmonary Embolism, Thrombocytopenia, Vascular Neoplasms, Venous Thromboembolism, Venous Thrombosis, Warfarin
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