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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2013 by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor:
Information provided by (Responsible Party):
P.W. Kamphuisen, University Medical Centre Groningen
ClinicalTrials.gov Identifier:
NCT01164046
First received: July 15, 2010
Last updated: May 24, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Venous Thromboembolism
Neoplasms
Drug: low molecular weight heparin
Drug: vitamin K antagonists
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
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

Resource links provided by NLM:


Further study details as provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):

Primary Outcome Measures:
  • Symptomatic recurrent VTE, i.e. the composite of recurrent deep venous thrombosis and fatal or non-fatal pulmonary embolism [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Primary efficacy outcome


Secondary Outcome Measures:
  • All clinically relevant bleeding (i.e. major bleeding and other clinically relevant non-major bleeding) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    safety outcome

  • all-cause mortality [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    safety outcome


Estimated Enrollment: 1000
Study Start Date: August 2010
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: vitamin K antagonists Drug: vitamin K antagonists
Target INR between 2-3. Any type allowed, if approved for use in that country.
Other Names:
  • phenprocoumon
  • acenocoumarol
  • warfarin
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
Other Names:
  • nadroparin
  • enoxaparin
  • tinzaparin
  • bemiparin
  • reviparin
  • dalteparin
  • certoparin

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with cancer and confirmed pulmonary embolism (PE) or deep vein thrombosis (DVT) of the leg who have been treated for minimally 6 and maximally 12 months with therapeutic doses of anticoagulants, i.e. LMWH or VKA or a new anticoagulant in a trial
  2. Written informed consent
  3. Indication for long-term anticoagulant therapy (e.g. because of metastasized disease, chemotherapy)

Exclusion Criteria:

  1. Legal age limitations (country specific), minimum age at least 18 years
  2. Indications for anticoagulant therapy other than DVT or PE
  3. Any contraindication listed in the local labeling of LMWH or VKA
  4. Childbearing potential without proper contraceptive measures, pregnancy or breastfeeding
  5. Life expectancy <3 months
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01164046

Contacts
Contact: Pieter W. Kamphuisen, Prof 0031503612943 p.w.kamphuisen@umcg.nl
Contact: Harry R. Buller, Prof 0031-205669111 H.R.Buller@amc.uva.nl

Locations
Italy
Ospedali Riuniti Recruiting
Bergamo, Italy
Contact: A. Falanga       annafalanga@yahoo.com   
Principal Investigator: A. Falanga, Prof.         
Hospital d'Annunziata Recruiting
Chieti, Italy
Contact: M. di Nisio, Dr.       mdinisio@unich.it   
Principal Investigator: M. di Nisio, Dr.         
Ospedaliera di Padova Recruiting
Padova, Italy
Contact: P. Prandoni, Prof.       paoloprandoni@tin.it   
Principal Investigator: P. Prandoni, Prof.         
Arcispedale Santa Maria Nuova (ASMN) Recruiting
Reggio Emilia, Italy
Contact: A. Ghirarduzzi, Prof.       Angelo.Ghirarduzzi@asmn.re.it   
Principal Investigator: A. Ghirarduzzi, Prof.         
Ospedale di Circolo Recruiting
Varese, Italy
Contact: A. Squizzato, Dr.       alexsquizzo@libero.it   
Principal Investigator: A. Squizzato, Dr.         
Netherlands
Flevoziekenhuis Recruiting
Almere, Netherlands
Contact: M. ten Wolde       m.tenwolde@amc.uva.nl   
Principal Investigator: M. ten Wolde, Dr.         
Sub-Investigator: V. Lustig, Dr.         
Academic Medical Centre (AMC) Recruiting
Amsterdam, Netherlands
Contact: P.W. Kamphuisen, Dr.       P.W.Kamphuisen@amc.uva.nl   
Principal Investigator: P.W. Kamphuisen, Dr.         
Slotervaart Hospital Recruiting
Amsterdam, Netherlands
Contact: H.M. Otten, Dr.       Hans-Martin.Otten@slz.nl   
Principal Investigator: H.M. Otten, Dr.         
Reinier de Graaf Groep Recruiting
Delft, Netherlands
Contact: E.F.M. Posthuma       Posthuma@rdgg.nl   
Principal Investigator: E.F.M. Posthuma, Dr.         
Medisch Spectrum Twente Recruiting
Enschede, Netherlands
Contact: M. de Groot, Dr.       M.deGroot@mst.nl   
Principal Investigator: M. de Groot, Dr.         
University Medical Centre Groningen (UMCG) Recruiting
Groningen, Netherlands
Contact: K. Meyer, Dr.       k.meijer@int.umcg.nl   
Principal Investigator: K. Meyer, Dr.         
Sponsors and Collaborators
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Investigators
Principal Investigator: Pieter W. Kamphuisen, MD, PhD University Medical Centre 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
  More Information

Publications:

Responsible Party: P.W. Kamphuisen, Prof, University Medical Centre Groningen
ClinicalTrials.gov Identifier: NCT01164046     History of Changes
Other Study ID Numbers: EudraCT nr: 2009-015336-15, Protocol nr: 29462
Study First Received: July 15, 2010
Last Updated: May 24, 2013
Health Authority: Netherlands: Medical Ethics Review Committee (METC)
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):
anticoagulants
Heparin, Low-Molecular-Weight
4-Hydroxycoumarins
recurrent venous thrombosis

Additional relevant MeSH terms:
Pulmonary Embolism
Thromboembolism
Thrombosis
Venous Thromboembolism
Venous Thrombosis
Cardiovascular Diseases
Embolism
Embolism and Thrombosis
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Calcium heparin
Dalteparin
Heparin
Heparin, Low-Molecular-Weight
Vitamin K
Vitamins
Anticoagulants
Antifibrinolytic Agents
Cardiovascular Agents
Coagulants
Fibrin Modulating Agents
Fibrinolytic Agents
Growth Substances
Hematologic Agents
Hemostatics
Micronutrients
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 21, 2014