Effectiveness of Bridging Anticoagulation for Surgery (The BRIDGE Study)

Atrial Fibrillation Clinical Trial

Official title:

Bridging Anticoagulation in Patients Who Require Temporary Interruption of Warfarin Therapy for an Elective Invasive Procedure or Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00786474
• Other study ID #: Pro00017344
• Secondary ID: 1U01HL086755-01A
• Status: Completed
• Phase: Phase 3
• First received: November 5, 2008
• Last updated: February 8, 2016
• Start date: July 2009
• Est. completion date: February 2015

Study information

• Verified date: January 2016
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 1884
• Est. completion date: February 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arterial Thromboembolic Events
• Atrial Fibrillation
• Thromboembolism

Intervention

Drug:
• Placebo
Normal saline solution, dosage determined by weight, self-administered by patient twice a day
• Dalteparin
Low molecular weight heparin (LMWH), dosage determined by weight, self-administered by patient twice a day

Locations

Country	Name	City	State
United States	Duke Clinical Research Institute	Durham	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Duke University	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Arterial Thromboembolic Events	The events are defined as arterial thromboembolism: stokes, transient ischemic attack and systemic embolism events were independently and blindly adjudicated	from subject signing of the consent until completed the study (Day -30 to Day +37)	Yes
Primary	Major Bleeding	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	from subject signing of the consent until completed the study (Day -30 to Day +37)	Yes
Secondary	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)	Yes
Secondary	Number of Participants With Minor Bleeding	Minor bleeding is defined as symptomatic or clinically-overt bleeding that does not satisfy the criteria for major bleeding	from subject signing of the consent until completed the study (Day -30 to Day +37)	Yes