Long-term Treatment for Cancer Patients With Deep Venous Thrombosis or Pulmonary Embolism (Longheva)
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.
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.
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.
This is a multicenter, multinational, randomized, open label trial.
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.
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.
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.
|Venous Thromboembolism Neoplasms||Drug: low molecular weight heparin Drug: vitamin K antagonists||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Long-term Treatment for Cancer Patients With Deep Venous Thrombosis or Pulmonary Embolism|
- Symptomatic recurrent VTE, i.e. the composite of recurrent deep venous thrombosis and fatal or non-fatal pulmonary embolism [ Time Frame: 6 months ]Primary efficacy outcome
- All clinically relevant bleeding (i.e. major bleeding and other clinically relevant non-major bleeding) [ Time Frame: 6 months ]safety outcome
- all-cause mortality [ Time Frame: 6 months ]safety outcome
|Study Start Date:||August 2010|
|Study Completion Date:||July 2014|
|Primary Completion Date:||July 2014 (Final data collection date for primary outcome measure)|
|Active Comparator: vitamin K antagonists||
Drug: vitamin K antagonists
Target INR between 2-3. Any type allowed, if approved for use in that country.
|Active Comparator: Low molecular weight heparin||
Drug: low molecular weight heparin
weight adjusted dose of low molecular weight heparin, any type allowed if approved, 65-75% of full therapeutic dose
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT01164046
|United States, District of Columbia|
|George Washington University|
|Washington, District of Columbia, United States, 20037|
|University Health Network|
|Toronto, Ontario, Canada|
|Medical Clinic Dresden University|
|Ospedaliera di Padova|
|Arcispedale Santa Maria Nuova (ASMN)|
|Reggio Emilia, Italy|
|Ospedale di Circolo|
|Academic Medical Centre (AMC)|
|Reinier de Graaf Groep|
|Medisch Spectrum Twente|
|University Medical Centre Groningen (UMCG)|
|Principal Investigator:||Pieter W. Kamphuisen, MD, PhD||University Medical Center Groningen|
|Principal Investigator:||Harry R. Buller, MD, PhD||Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)|
|Study Chair:||Steering Board Committee||Representatives from participating centers|