Long-term Treatment for Cancer Patients With Deep Venous Thrombosis or Pulmonary Embolism
Status:
Terminated
Trial end date:
2014-07-01
Target enrollment:
Participant gender:
Summary
Background
Patients with cancer and a first deep venous thrombosis of the leg or pulmonary embolism
(venous thromboembolism, VTE) are generally treated with low molecular weight heparin
(LMWH)injections for 6 months, since this treatment is associated with a reduced incidence of
recurrent VTE compared to vitamin K antagonists (VKA). It is recommended that patients with
active malignancy (metastatic cancer and/or ongoing cancer treatment)continue anticoagulant
treatment. However, it is unknown whether LMWH is still superior compared to VKA for the
long-term anticoagulant treatment.
Aim
The aim of this study is to evaluate whether low-molecular-weight heparin more effectively
reduces recurrent VTE compared to vitamin K antagonists in patients with cancer who have
already completed 6 to 12 months of anticoagulant treatment because of deep venous thrombosis
of the leg or pulmonary embolism.
Hypothesis
The investigators hypothesize that LMWH is more effective compared to VKA in the long-term
treatment of VTE in cancer patients who have already been treated for 6-12 months with
anticoagulants.
Design
This is a multicenter, multinational, randomized, open label trial.
Patients
Patients with a malignancy (all types, solid and hematological) who have received 6-12 months
of anticoagulation for VTE and have an indication for continuing anticoagulation, will be
randomly assigned to six additional months of LMWH or VKA. LMWH will be administered in a
weight-adjusted scheme, with 65-75% of therapeutic doses. All types of LMWH and VKA are
allowed, as long as weight adjusted dosing is possible for LMWH. The target INR will be
2.0-3.0. The primary efficacy outcome is symptomatic recurrent VTE, i.e. deep vein thrombosis
and pulmonary embolism. The primary safety outcome is major bleeding.
Sample size
A total of 65 to 87 recurrent VTE events are needed to show a 50% reduction with LMWH as
compared to VKA (type I error 0.05, two-sided, power respectively 80 and 90%). To observe 75
events, with a 10% event rate per half year in the VKA arm and 5% in the LMWH arm a total of
1000 patients will need to be included.
Organisation
Outcomes will be adjudicated by a central adjudication committee. A steering committee will
be formed, preferably consisting of one member of every participating center. An electronic
case report form will be used for data collection. Also, an electronic trial master file will
be used.