Effectiveness of Bridging Anticoagulation for Surgery (The BRIDGE Study)

Phase 3

Completed

Conditions: Arterial Thromboembolic Events
Atrial Fibrillation

Interventions: Drug: Placebo
Drug: Dalteparin

Registration Number: NCT00786474

Lead Sponsor: Duke University

Brief Summary: Blood thinners, such as warfarin, prevent blood clots from forming, thereby reducing the risk of a stroke or heart attack. When people undergo surgery or certain procedures, they must stop using warfarin to prevent too much bleeding during and after the surgery or procedure. Some doctors prescribe a different blood thinner, one that works more quickly and wears off more quickly, to bridge the gap between starting and stopping warfarin. However, this short-term treatment is expensive, may increase the risk of bleeding, and has not been proven effective. This study will determine whether a bridging blood thinner called dalteparin is helpful or harmful for people with atrial fibrillation who stop taking warfarin in preparation for surgery or a procedure.

Detailed Description: Approximately 2 million people in North America take the anticoagulant warfarin to prevent stroke, heart attack, and other events related to blood clots. Warfarin needs to be stopped before a person undergoes surgery or certain procedures because it can cause dangerous amounts of bleeding during and after surgery. Some doctors give a low molecular weight heparin (LMWH) to patients during the 2-week period when participants are without the effects of warfarin. The LMWH has the same effect as warfarin, but it acts and then leaves the system more quickly than warfarin. However, the LMWH is expensive, may increase the risk of bleeding, and has not been proven effective. This study will determine the safety and efficacy of an LMWH in adults with atrial fibrillation who stop warfarin in preparation for surgery.

Participation in this study will last between 36 and 67 days. Participation will involve nine points of contact with researchers, at least two of which will be in-person visits at the research clinic. The others will be conducted by phone. All points of contact will include assessments on possible bleeding and any new symptoms. The first two of these points of contact, will take place at the signing of the informed consent, which will involve a screening of medical records and random assignment of participants to receive either the LMWH dalteparin or placebo. Participants will self-administer a subcutaneous injection of their assigned treatment twice a day for 3 days before the surgery or procedure and for 6 days after. During the course of the study, when participants visit their primary physicians for regularly scheduled appointments, it will be recommended that they undergo two international normalized ratio (INR) tests of blood clotting ability between day 2 and 10 after the surgery or procedure. The remaining seven points of contact will occur sometime between the day before surgery and 37 days after surgery. One of the in-person visits will occur within the first week after surgery and will include assessments on possible bleeding, any new symptoms, and INR results.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1884

Inclusion Criteria

Receiving warfarin therapy for at least 3 months, administered to achieve an international normalized ratio (INR) range of 2.0 to 3.0
Requiring temporary interruption of warfarin for pre-specified elective procedure or surgery
Presence of one of the following conditions:
1. Chronic (permanent or paroxysmal) nonvalvular atrial fibrillation, confirmed by at least one prior electrocardiography recording or pacemaker or acid citrate dextrose (ACD) interrogation
2. Chronic (permanent or paroxysmal) valvular atrial fibrillation with evidence of mitral valvular heart disease, confirmed by the same criteria as nonvalvular atrial fibrillation
Presence of at least one of the following major stroke risk factors:
1. Older than 75 years of age
2. Hypertension
3. Diabetes mellitus
4. Congestive heart failure or left ventricular dysfunction
5. Previous ischemic stroke, systemic embolism, or transient ischemic attack (TIA)

Exclusion Criteria

Any mechanical prosthetic heart valve
Stroke (ischemic or hemorrhagic), systemic embolism, or TIA within the past 12 weeks
Venous thromboembolism (deep vein thrombosis and/or pulmonary embolism) within past 12 weeks
Major bleeding within the past 6 weeks
Severe renal insufficiency, measured through a calculated creatinine clearance of less than 30 mL/min
Thrombocytopenia
Life expectancy less than 1 month
Condition that impairs compliance with trial protocol, such as cognitive impairment, an uncontrolled psychiatric condition, or geographic inaccessibility
Pregnancy
Allergy to heparin or history of heparin-induced thrombocytopenia
Having one of the following surgeries or procedures during warfarin interruption:
1. Cardiac surgery, such as coronary artery bypass or heart valve replacement
2. Neurosurgery that is intracranial or intraspinal, such as tumor resection or aneurysm repair
3. High-risk non-surgical procedures, such as brain biopsy
Other surgical or non-surgical procedure that, at the discretion of the surgeon, precludes administration of therapeutic-dose low molecular weight heparin (LMWH) at any time in the post-procedure period
More than one surgery planned during the trial period
Prior participation in this trial

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
Dalteparin	Dalteparin	-

Primary Outcome Measures

Name	Time	Method
Number of Arterial Thromboembolic Events	from subject signing of the consent until completed the study (Day -30 to Day +37)	The events are defined as arterial thromboembolism: stokes, transient ischemic attack and systemic embolism events were independently and blindly adjudicated
Major Bleeding	from subject signing of the consent until completed the study (Day -30 to Day +37)	Major bleeding is defined as symptomatic bleeding associated with transfusion of more than two units of packed red blood cells or whole blood, or death

Secondary Outcome Measures

Name	Time	Method
Number of Subjects With Death, Acute Myocardial Infarction, Deep Vein Thrombosis, or Pulmonary Embolism	from subject signing of the consent until completed the study (Day -30 to Day +37)
Number of Participants With Minor Bleeding	from subject signing of the consent until completed the study (Day -30 to Day +37)	Minor bleeding is defined as symptomatic or clinically-overt bleeding that does not satisfy the criteria for major bleeding