Anticoagulant Clinics and Vitamin K Antagonists

NCT ID: NCT00966290

Last Updated: 2009-08-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 1006 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-02-28
• Study Completion Date: 2006-12-31

Brief Summary

Background: Whether the management of vitamin K antagonists (VKA) therapy by general practitioners with the collaboration of anticoagulation clinics (ACC) provides better clinical outcomes than that accomplished by general practitioners alone (usual care [UC] management) is not clear.

Objectives: To compare ACC-based shared-care management with UC management of VKA therapy with respect to clinical events.

Patients/Methods: Open, randomized, multicenter study in patients starting VKA therapy for at least three months. The primary study outcome is a composite of confirmed symptomatic thromboembolic or major bleeding events. All-cause mortality is a secondary outcome. All outcomes are reviewed by a central, independent adjudication committee.

Detailed Description

Study design

The COMPARE (Comparison of Oral anticoagulation Monitoring Practice: A Randomized Evaluation) study is an open, centrally randomized, multicenter, prospective, controlled study comparing two models of vitamin K antagonist (VKA) therapy management. Written informed consent is obtained from each patient and general practitioner before randomization.

Setting and participants

The study concerned patients referred to the anticoagulation clinic (ACC) of various University Hospitals in France. Eligible patients are consecutive patients who were starting a course of VKA therapy scheduled to last for at least three months.

Randomization and interventions

All eligible patients are evaluated by a physician specialized in vascular medicine or hematology. After their demographic characteristics and medical history had been recorded, they are randomized to one of the models of VKA therapy management, either UC management or ACC-based shared-care management. Randomization is stratified by center; the list of randomization is computer-generated according to a permuted block design with a block size of four, six or eight. General practitioners are informed of the outcome of randomization by a standardized letter. In patients randomized to the UC management group, the monitoring of VKA therapy is left to the general practitioner's discretion according to his/her preferences and habits. Patients randomized to the ACC-based shared-care management group receive a standardized educational package; moreover, each biological laboratory measuring INR values for the patients of this group is contacted to explain the importance of rapid restitution of the results. A computer-generated dose proposal is also given, both by telephone and by fax, to the general practitioners who follow up patients randomized to the ACC-based shared-care management group; however, they were free to accept or ignore this proposal. All patients receive a logbook in which to record their INR results.

Study outcomes

The primary study outcome is a composite of symptomatic and objectively confirmed thromboembolic or major bleeding events at 18 months. Thromboembolic events are acute myocardial infarction, stroke, peripheral arterial occlusion, deep-vein thrombosis or pulmonary embolism. Major bleeding events are fatal bleeding, or any bleeding leading to functional impairment or requiring hospitalization. All-cause mortality is a secondary outcome measure. All outcomes are reviewed by a central, independent adjudication committee, the members of which were unaware of the patients' study group.

The quality of anticoagulation control is evaluated in all randomized patients with at least two INR measurements. This parameter is assessed by determining (1) the percentage of INR within the target range, (2) the percentage of time during which the INR was within the target range in relation to the total length of the observation period, according to the linear interpolation method, and (3) the variability index (σ2).

Statistical analysis

This is a superiority study in which we hypothesize that ACC-based shared-care management would reduce the cumulative incidence of the primary study outcome by 50% compared with UC management. On the basis of previous non-controlled studies, we assumed that the cumulative incidence of the primary study outcome would be 10% in patients assigned to the UC management group. Given these assumptions, we calculated that the recruitment of 600 patients per group would allow confirmation of the statistical hypothesis with 90% power and a two-sided, type I error of 0.05.

The statistical analyses will be performed on all randomized patients on an intention-to-treat basis.

Conditions

Blood Coagulation Disorders

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ACC group

Anticoagulant clinic-based shared-care group

Group Type: EXPERIMENTAL

Anticoagulant (warfarin, acenocoumarol, fluindione)

Intervention Type: DRUG

Anticoagulant clinic based shared-care group

UC group

Usual care group

Group Type: ACTIVE_COMPARATOR

Anticoagulant (warfarin, acenocoumarol, fluindione)

Intervention Type: DRUG

Usual care group

Interventions

Anticoagulant (warfarin, acenocoumarol, fluindione)

Anticoagulant clinic based shared-care group

Intervention Type: DRUG

Anticoagulant (warfarin, acenocoumarol, fluindione)

Usual care group

Intervention Type: DRUG

Other Intervention Names

Patients whose anticoagulation is managed by the general practitioner in collaboration with anticoagulant clinic; Patients whose anticoagulation is managed by the general practitioner

Eligibility Criteria

Inclusion Criteria

• inpatients and outpatients who are starting a course of VKA therapy scheduled to last for at least three months

Exclusion Criteria

• life expectancy of less than three months
• contraindication to anticoagulant therapy because of bleeding risk
• refusal of his/her general practitioner to participate in the study
• no general practitioner likelihood of poor follow-up or poor compliance (e.g., patients unable to care for themselves, lacking adequate home support or unwilling to comply with the treatment care plan)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Toulouse

OTHER

Sponsor Role: lead

Responsible Party

University Hospital Toulouse

Principal Investigators

Henri Boccalon, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Toulouse

Alessandra BURA-RIVIERE, MD

Role: STUDY_DIRECTOR

University Hospital, Toulouse

Patrick Mismetti, MD

Role: STUDY_DIRECTOR

University Hospital Saint-Etienne

Bernard Boneu, MD

Role: STUDY_DIRECTOR

University Hospital, Toulouse

Locations

University Hospital

Brest, , France

Louis Pasteur Hospital

Dole, , France

University Hospital

Lille, , France

Dupuytren University Hospital

Limoges, , France

Bellevue University Hospital

Saint-Etienne, , France

University Hospital

Strasbourg, , France

Rangueil University Hospital

Toulouse, , France

Countries

France

Other Identifiers

PHRC 2002

Identifier Type: -

Identifier Source: secondary_id

0200301

Identifier Type: -

Identifier Source: org_study_id