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Tapered Warfarin or Interrupted Warfarin With Heparin Bridging for Pacemaker or Defibrillator Implantation (PACEBRIDGE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02094157
Recruitment Status : Terminated (Change of practice made further recruitment impossible)
First Posted : March 21, 2014
Last Update Posted : April 5, 2016
Information provided by (Responsible Party):
McMaster University

Brief Summary:
Approximately 2 million patients in North America are currently treated with the blood thinner warfarin. These patients have every year more than 200,000 invasive procedures, for which warfarin must be stopped to avoid bleeding complication. To protect the patient against blood clots and stroke while warfarin is stopped, most physicians today order "bridging" with low-molecular-weight heparin (LMWH). This is another blood thinner and it is injected under the skin during 3 days before the procedure. For implantation of pacemaker or defibrillator (27,000/year in Canada) the "bridging" routines vary a lot.The common "bridging" treatment with LMWH for 3 days before pacemaker surgery causes bleeding in the "pocket" where the pacemaker is placed in about 5%. For comparison, patients not on any blood thinners develop this bleeding in 2% after this surgery. "Pocket bleeding" may require evacuation of the blood collection and may cause infection. "Pocket bleeding" is thus a fairly common and clinically important but rarely a dangerous bleeding complication. It is a suitable safety endpoint in a study of "bridging" of blood thinners. LMWH costs $80-120, for which some patients are not covered. They have to be taught self-injection technique or have a nurse come to their home. The main hypothesis is if patients on blood thinners can be managed more conveniently before and after pacemaker surgery, without injections, without increased risk of pocket bleeding.

Condition or disease Intervention/treatment Phase
Cardiac Arrhythmias Hemorrhage Thromboembolism Drug: Tapered warfarin regimen Drug: Bridged regimen Low-molecular-weight heparin Phase 3

Detailed Description:
Patients are recruited from those routinely referred before surgery for adjustment of their blood thinners. Suitable and consenting patients are randomized to one of the two regimens. They will either stop warfarin for 5 days and replace it with injections of LMWH for 3 days before pacemaker or implantable cardioverter defibrillator (ICD) surgery. The other group will have the dose of warfarin reduced to half for 3-6 days before surgery, depending on how thin their blood is. For all patients the degree of blood thinning is checked the day before surgery. If the blood is still to thin, the patient is instructed to take by mouth a dose of vitamin K, provided by us, to reduce the effect of warfarin. After surgery the patients restart warfarin at a double dose for 1 or 2 days to quickly reach the therapeutic effect again. Staff from the Pacemaker or Defibrillator Clinic, unaware of the treatment allocation, examines the patient for bleeding in the implantation pocket before they leave the hospital, and at routine follow-up after 2-3 weeks and 90 days.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 173 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: An Open-Label Randomized Control Trial of Pre-Operative Low Molecular Weight Heparin Versus Tapered Warfarin as Bridging Therapy for Patients With Implantation of Pacemaker or Defibrillator
Study Start Date : December 2007
Actual Primary Completion Date : November 2013
Actual Study Completion Date : March 2014

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: Bridged regimen
Bridged regimen Warfarin therapy is stopped for 5 days before surgery and restarted in the evening of surgery at double the usual dose for two days. Bridging with low-molecular-weight heparin at therapeutic dose is given for 2½ days before surgery.
Drug: Bridged regimen Low-molecular-weight heparin
This intervention is assigned to the active control arm - Bridged regimen
Other Name: Low-molecular-weight heparin

Experimental: Tapered warfarin regimen
Tapered warfarin regimen Warfarin is given at half the usual maintenance dose for 3-6 days before surgery depending on the INR at the baseline visit. A double dose is given in the evening of surgery. No bridging with LMWH is used.
Drug: Tapered warfarin regimen
This intervention is assigned to the experimental arm - Tapered warfarin regimen
Other Name: Half dose warfarin

Primary Outcome Measures :
  1. Pocket hematoma [ Time Frame: 1 month ]
    Pocket hematoma is defined as palpable swelling of the pacemaker or defibrillator pocket exceeding the size of the generator.

Secondary Outcome Measures :
  1. Major bleeding [ Time Frame: 1 month ]
    Fatal bleeding OR Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome OR Bleeding causing a fall in hemoglobin level of 20 g·L-1 (1.24 mmol·L-1) or more, or leading to transfusion of two or more units of whole blood or red cells.

  2. Thromboembolism [ Time Frame: 1 month ]
    Arterial thromboembolism, consisting of one or more of the following: stroke (ischemic or hemorrhagic), transient ischemic attack, systemic embolism to a limb or viscus, thrombosis of a mechanical or native heart valve, or thrombosis of a cardiac chamber. OR Venous thromboembolism that is symptomatic AND for deep vein thrombosis is verified by ultrasound, venography or computed tomography; for pulmonary embolism is verified by ventilation-perfusion lung scan, spiral computed tomography or pulmonary angiography.

Other Outcome Measures:
  1. Preoperative reversal with vitamin K [ Time Frame: 1 day ]
    Patients with International Normalized Ratio (INR) above 1.7 the day before surgery require correction of the coagulopathy with vitamin K to allow for surgery.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • The patient has been receiving warfarin therapy for at least 1 week and is planned to continue this treatment for at least one month post-procedure
  • The patient will have elective implantation or replacement of a pacemaker or ICD

Exclusion Criteria:

  • Age <18 years
  • Previous stroke
  • Stroke risk (CHADS2) score of 0 or 1 in patients with atrial fibrillation as the only indication for anticoagulation
  • Creatinine clearance (CrCl) <30 mL/min
  • Surgery planned for a Monday or a day after a holiday
  • Patient unsuitable for the study as assessed by the investigator (e.g., psychiatric disorder, history of non-compliance)
  • Failure to obtain written consent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02094157

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Canada, Ontario
Hamilton Health Sciences-General Hospital
Hamilton, Ontario, Canada, L8L 2X2
St. Joseph's Healthcare
Hamilton, Ontario, Canada, L8N 4A6
Sponsors and Collaborators
McMaster University
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Principal Investigator: Sam Schulman, MD, PhD McMaster University

Publications of Results:
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Responsible Party: McMaster University Identifier: NCT02094157     History of Changes
Other Study ID Numbers: PB 20080717
First Posted: March 21, 2014    Key Record Dates
Last Update Posted: April 5, 2016
Last Verified: April 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by McMaster University:
Atrial fibrillation
Mechanical heart valve
Venous thromboembolism
Additional relevant MeSH terms:
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Arrhythmias, Cardiac
Pathologic Processes
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Heart Diseases
Calcium heparin
Heparin, Low-Molecular-Weight
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action