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Effectiveness of Bridging Anticoagulation for Surgery (The BRIDGE Study)

Primary Purpose

Arterial Thromboembolic Events, Atrial Fibrillation

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Placebo
Dalteparin
Sponsored by
Duke University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Arterial Thromboembolic Events focused on measuring Bridging Anticoagulation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Duke Clinical Research Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Dalteparin

Arm Description

Outcomes

Primary Outcome Measures

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
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

Secondary Outcome Measures

Number of Subjects With Death, Acute Myocardial Infarction, Deep Vein Thrombosis, or Pulmonary Embolism
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

Full Information

First Posted
November 5, 2008
Last Updated
February 8, 2016
Sponsor
Duke University
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
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1. Study Identification

Unique Protocol Identification Number
NCT00786474
Brief Title
Effectiveness of Bridging Anticoagulation for Surgery (The BRIDGE Study)
Official Title
Bridging Anticoagulation in Patients Who Require Temporary Interruption of Warfarin Therapy for an Elective Invasive Procedure or Surgery
Study Type
Interventional

2. Study Status

Record Verification Date
January 2016
Overall Recruitment Status
Completed
Study Start Date
July 2009 (undefined)
Primary Completion Date
February 2015 (Actual)
Study Completion Date
February 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Duke University
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Arterial Thromboembolic Events, Atrial Fibrillation
Keywords
Bridging Anticoagulation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
1884 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Title
Dalteparin
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Normal saline solution, dosage determined by weight, self-administered by patient twice a day
Intervention Type
Drug
Intervention Name(s)
Dalteparin
Other Intervention Name(s)
Fragmin
Intervention Description
Low molecular weight heparin (LMWH), dosage determined by weight, self-administered by patient twice a day
Primary Outcome Measure Information:
Title
Number of Arterial Thromboembolic Events
Description
The events are defined as arterial thromboembolism: stokes, transient ischemic attack and systemic embolism events were independently and blindly adjudicated
Time Frame
from subject signing of the consent until completed the study (Day -30 to Day +37)
Title
Major Bleeding
Description
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
Time Frame
from subject signing of the consent until completed the study (Day -30 to Day +37)
Secondary Outcome Measure Information:
Title
Number of Subjects With Death, Acute Myocardial Infarction, Deep Vein Thrombosis, or Pulmonary Embolism
Time Frame
from subject signing of the consent until completed the study (Day -30 to Day +37)
Title
Number of Participants With Minor Bleeding
Description
Minor bleeding is defined as symptomatic or clinically-overt bleeding that does not satisfy the criteria for major bleeding
Time Frame
from subject signing of the consent until completed the study (Day -30 to Day +37)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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: Chronic (permanent or paroxysmal) nonvalvular atrial fibrillation, confirmed by at least one prior electrocardiography recording or pacemaker or acid citrate dextrose (ACD) interrogation 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: Older than 75 years of age Hypertension Diabetes mellitus Congestive heart failure or left ventricular dysfunction 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: Cardiac surgery, such as coronary artery bypass or heart valve replacement Neurosurgery that is intracranial or intraspinal, such as tumor resection or aneurysm repair 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas L. Ortel, MD
Organizational Affiliation
Duke University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Victor Hasselblad, PhD
Organizational Affiliation
Duke Clinical Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Duke Clinical Research Institute
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27715
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
27280017
Citation
Wight JM, Columb MO. Perioperative bridging anticoagulation for atrial fibrillation-the first randomised controlled trial. Perioper Med (Lond). 2016 Jun 7;5:14. doi: 10.1186/s13741-016-0040-5. eCollection 2016.
Results Reference
derived
PubMed Identifier
26095867
Citation
Douketis JD, Spyropoulos AC, Kaatz S, Becker RC, Caprini JA, Dunn AS, Garcia DA, Jacobson A, Jaffer AK, Kong DF, Schulman S, Turpie AG, Hasselblad V, Ortel TL; BRIDGE Investigators. Perioperative Bridging Anticoagulation in Patients with Atrial Fibrillation. N Engl J Med. 2015 Aug 27;373(9):823-33. doi: 10.1056/NEJMoa1501035. Epub 2015 Jun 22.
Results Reference
derived
PubMed Identifier
22244711
Citation
Assaad B, Sesi VK, Figari R, Schultz L, Thummala N, Rehman M, Chandok A, Silverman A, Silver B. Antithrombotic management of stroke patients before colonoscopy. J Stroke Cerebrovasc Dis. 2013 Aug;22(6):733-6. doi: 10.1016/j.jstrokecerebrovasdis.2011.12.006. Epub 2012 Jan 12.
Results Reference
derived

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Effectiveness of Bridging Anticoagulation for Surgery (The BRIDGE Study)

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