Long-term Treatment for Cancer Patients With Deep Venous Thrombosis or Pulmonary Embolism

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.

Conditions

• Venous Thromboembolism
• Neoplasms

Interventions

DRUG

low molecular weight heparin

weight adjusted dose of low molecular weight heparin, any type allowed if approved, 65-75% of full therapeutic dose

DRUG

vitamin K antagonists

Target INR between 2-3. Any type allowed, if approved for use in that country.

Sponsors & Collaborators

• University Medical Center Groningen

  lead OTHER

Principal Investigators

• Pieter W. Kamphuisen, MD, PhD · University Medical Center Groningen

• Harry R. Buller, MD, PhD · Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

• Steering Board Committee · Representatives from participating centers

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2010-08-31

Primary Completion

2014-07-31

Completion

2014-07-31

Countries

• United States
• Canada
• Germany
• Italy
• Netherlands

Study Locations