Tapered Warfarin or Interrupted Warfarin With Heparin Bridging for Pacemaker or Defibrillator Implantation

Hemorrhage Clinical Trial

— PACEBRIDGE  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02094157
• Other study ID #: PB 20080717
• Status: Terminated
• Phase: Phase 3
• First received: March 19, 2014
• Last updated: April 1, 2016
• Start date: December 2007
• Est. completion date: March 2014

Study information

• Verified date: April 2016
• Source: McMaster University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health CanadaCanada: Ethics Review Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 173
• Est. completion date: March 2014
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arrhythmias, Cardiac
• Cardiac Arrhythmias
• Hemorrhage
• Thromboembolism

Intervention

Drug:
• Tapered warfarin regimen
This intervention is assigned to the experimental arm - Tapered warfarin regimen
• Bridged regimen Low-molecular-weight heparin
This intervention is assigned to the active control arm - Bridged regimen

Locations

Country	Name	City	State
Canada	Hamilton Health Sciences-General Hospital	Hamilton	Ontario
Canada	St. Joseph's Healthcare	Hamilton	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
McMaster University

Country where clinical trial is conducted

Canada, 

References & Publications (1)

Schulman S, Healey JS, Douketis JD, Delaney J, Morillo CA. Reduced-dose warfarin or interrupted warfarin with heparin bridging for pacemaker or defibrillator implantation: a randomized trial. Thromb Res. 2014 Oct;134(4):814-8. doi: 10.1016/j.thromres.2014 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Preoperative reversal with vitamin K	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.	1 day	No
Primary	Pocket hematoma	Pocket hematoma is defined as palpable swelling of the pacemaker or defibrillator pocket exceeding the size of the generator.	1 month	Yes
Secondary	Major bleeding	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.	1 month	Yes
Secondary	Thromboembolism	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.	1 month	No