Clinical trial NCT00203580: 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)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Thrombosis
Thromboembolism
Venous Thrombosis
Keywords: venous thromboembolism
low-molecular-weight heparin
Lead sponsor: University of Calgary
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: LEO Pharma
name: Dupont Applied Biosciences
First posted: 2005-09-20
Enrollment: 910
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: objectively documented recurrent venous thromboembolism during initial treatment or during the 12 week follow-up period
measure: death during initial treatment or during the 12 week follow-up period
measure: safety endpoint for assessing harm was the occurrence of bleeding (all, major or minor) during the 12 week treatment interval
Secondary outcomes:
measure: recurrent venous thromboembolism at 12 months
measure: death at 12 months
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Thrombosis Research Unit, University of Calgary
state: Alberta
Study officials:
affiliation: University of Calgary
name: Russell D Hull, MBBS, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1056/NEJM199603143341102.
citation: 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. doi: 10.1056/NEJM199603143341101.
citation: 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.
citation: Laird NM, Ware JH. Random-effects models for longitudinal data. Biometrics. 1982 Dec;38(4):963-74.