This trial is active, not recruiting.

Conditions arterial thromboembolic events, atrial fibrillation
Treatments placebo, dalteparin
Phase phase 3
Sponsor Duke University
Collaborator National Heart, Lung, and Blood Institute (NHLBI)
Start date July 2009
End date March 2015
Trial size 1882 participants
Trial identifier NCT00786474, 1U01HL086755-01A1, 1U01HL087229, Pro00017344


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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator)
Primary purpose treatment
(Placebo Comparator)
Normal saline solution, dosage determined by weight, self-administered by patient twice a day
dalteparin Fragmin
Low molecular weight heparin (LMWH), dosage determined by weight, self-administered by patient twice a day

Primary Outcomes

Arterial thromboembolic events, defined as an ischemic stroke, transient ischemic attack, or systemic embolism
time frame: Measured throughout the study
Major bleeding, symptomatic bleeding associated with transfusion of more than two units of packed red blood cells or whole blood, or death
time frame: Measured throughout the study

Secondary Outcomes

Acute myocardial infarction, deep vein thrombosis, or pulmonary embolism
time frame: Measured throughout the study
Minor bleeding
time frame: Measured throughout the study

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

Official title Bridging Anticoagulation in Patients Who Require Temporary Interruption of Warfarin Therapy for an Elective Invasive Procedure or Surgery
Principal investigator Thomas L. Ortel, MD
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.
Trial information was received from ClinicalTrials.gov and was last updated in January 2015.
Information provided to ClinicalTrials.gov by Duke University.