Trial of the Effect of Low-Molecular-Weight Heparin (LMWH) Versus Warfarin on Mortality in the Long-Term Treatment of Proximal Deep Vein Thrombosis (DVT) (Main LITE Study)

• ClinicalTrials.gov Identifier: NCT00203580
• Recruitment Status: Completed
• First Posted: September 20, 2005
• Last Update Posted: February 9, 2007
• Sponsor: University of Calgary
• Collaborators: Canadian Institutes of Health Research (CIHR); LEO Pharma; Dupont Applied Biosciences
• Information provided by: University of Calgary

Study Description

Brief Summary:

The purpose of this study is to assess the long-term treatment of patients with proximal venous thrombosis through the administration of subcutaneous low-molecular-weight heparin (tinzaparin sodium) versus the standard care use of intravenous heparin followed by oral warfarin sodium.

Condition or disease	Intervention/treatment	Phase
Thrombosis; Thromboembolism; Venous Thrombosis	Drug: Tinzaparin sodium	Phase 4

Detailed Description:

The accepted treatment for acute deep vein thrombosis (DVT) is initial continuous intravenous heparin followed by long-term oral anticoagulant therapy. Improvements in the methods of clinical trials and the use of accurate objective tests to detect venous thromboembolism have made it possible to perform a series of randomized trials to evaluate various treatments of venous thromboembolism.

The specific objectives of the Main LITE Study are:

• to determine if low-molecular-weight heparin, given subcutaneously once daily without laboratory monitoring, is more effective than adjusted oral warfarin sodium in the reduction of mortality rate.
• to determine if such a low-molecular-weight heparin therapy is more cost-effective than present standard care methods.
• to determine the incidence of Factor V Leiden and Prothrombin 20210A mutant genetic abnormalities.

Study Design

• Study Type: Interventional (Clinical Trial)
• Enrollment: 910 participants
• Allocation: Randomized
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Trial of the Effect of Low-Molecular-Weight Heparin Versus Warfarin Sodium on the Mortality in the Long-Term Treatment of Proximal Deep Vein Thrombosis (Main LITE Study)
• Study Start Date: December 1994
• Study Completion Date: March 2002

Arms and Interventions

Outcome Measures

Primary Outcome Measures :

1. objectively documented recurrent venous thromboembolism during initial treatment or during the 12 week follow-up period
2. death during initial treatment or during the 12 week follow-up period
3. safety endpoint for assessing harm was the occurrence of bleeding (all, major or minor) during the 12 week treatment interval

Secondary Outcome Measures :

1. recurrent venous thromboembolism at 12 months
2. death at 12 months

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patients having a first or recurrent episode of acute proximal vein thrombosis

Exclusion Criteria:

• Presence of familial bleeding diathesis or presence of active bleeding contraindicating anticoagulant therapy
• Receiving therapeutic heparin or therapeutic low-molecular-weight heparin for more than 48 hours or have already been on warfarin for more than 2 days for the treatment of proximal deep vein thrombosis
• Receiving long-term warfarin treatment
• Females who are pregnant
• Known allergy to heparin, warfarin sodium, or bisulfites
• History of heparin-associated thrombocytopenia
• Severe malignant hypertension
• Hepatic encephalopathy
• Severe renal failure
• Inability to attend follow-up due to geographic inaccessibility
• Inability or refusal to give informed consent
• Recent neurological or opthalmic surgery (within the previous 14 days)
• Pulmonary embolism requiring thrombolytic therapy, surgical thrombectomy, or vena cava interruption
• Life expectancy of less than 3 months
• Taking ASA prior to randomization and unable to discontinue this medication during the 84 day study treatment period

Contacts and Locations

Locations

Canada, Alberta

Thrombosis Research Unit, University of Calgary

Calgary, Alberta, Canada, T2N 2T9

Sponsors and Collaborators

University of Calgary

Canadian Institutes of Health Research (CIHR)

LEO Pharma

Dupont Applied Biosciences

Investigators

• Principal Investigator: Russell D Hull, MBBS, MSc; University of Calgary

More Information

Publications:

Koopman MM, Prandoni P, Piovella F, Ockelford PA, Brandjes DP, van der Meer J, Gallus AS, Simonneau G, Chesterman CH, Prins MH. Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecular-weight heparin administered at home. The Tasman Study Group. N Engl J Med. 1996 Mar 14;334(11):682-7. Erratum in: N Engl J Med 1997 Oct 23;337(17):1251.

Levine M, Gent M, Hirsh J, Leclerc J, Anderson D, Weitz J, Ginsberg J, Turpie AG, Demers C, Kovacs M. A comparison of low-molecular-weight heparin administered primarily at home with unfractionated heparin administered in the hospital for proximal deep-vein thrombosis. N Engl J Med. 1996 Mar 14;334(11):677-81.

Lancaster TR, Singer DE, Sheehan MA, Oertel LB, Maraventano SW, Hughes RA, Kistler JP. The impact of long-term warfarin therapy on quality of life. Evidence from a randomized trial. Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators. Arch Intern Med. 1991 Oct;151(10):1944-9. Erratum in: Arch Intern Med 1992 Apr;152(4):825.

Laird NM, Ware JH. Random-effects models for longitudinal data. Biometrics. 1982 Dec;38(4):963-74.

• ClinicalTrials.gov Identifier: NCT00203580 History of Changes
• Other Study ID Numbers: 2736-1
• First Posted: September 20, 2005
• Last Update Posted: February 9, 2007
• Last Verified: September 2005

Keywords provided by University of Calgary:

venous thromboembolism; low-molecular-weight heparin

Additional relevant MeSH terms:

Thrombosis; Thromboembolism; Venous Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Heparin; Calcium heparin; Heparin, Low-Molecular-Weight; Dalteparin; Tinzaparin; Warfarin; Anticoagulants; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action