CLOT
Trial question
Is LMWH superior to coumarin for the prevention of recurrent VTE in patients with cancer?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
51.0% female
49.0% male
N = 676
676 patients (348 female, 328 male).
Inclusion criteria: patients with cancer who had acute, symptomatic proximal DVT, PE, or both.
Key exclusion criteria: weight ≤ 40 kg, ECOG performance status score of 3 or 4, receipt of OAC therapy, serious bleeding within the previous two weeks, high risk of serious bleeding, contraindications to heparin therapy, or pregnancy.
Interventions
N=338 subcutaneous dalteparin (200 IU of dalteparin per kilogram once daily for the first month and approximately 150 IU per kilogram for the remaining 5 months).
N=338 oral anticoagulation (dalteparin at a dose of 200 IU per kilogram of body weight SC once daily for 5-7 days and VKA for 6 months).
Primary outcome
Recurrent venous thromboembolism at 6 months
9%
17%
17.0 %
12.8 %
8.5 %
4.3 %
0.0 %
Subcutaneous
dalteparin
Oral
anticoagulation
Significant
decrease ▼
NNT = 12
Significant decrease in recurrent VTE at 6 months (9% vs. 17%; HR 0.48, 95% CI 0.3 to 0.77).
Secondary outcomes
No significant difference in death (39% vs. 41%; RR 0.95, 95% CI -1.94 to 3.84).
Safety outcomes
No significant difference in rate of major bleeding (6% vs. 4%) or any bleeding (14% vs. 19%).
Conclusion
In patients with cancer who had acute, symptomatic proximal DVT, PE, or both, subcutaneous dalteparin was superior to oral anticoagulation with respect to recurrent VTE at 6 months.
Reference
Lee AY, Levine MN, Baker RI et al. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med. 2003 Jul 10;349(2):146-53.
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