Clinical trial NCT02094157: Tapered Warfarin or Interrupted Warfarin With Heparin Bridging for Pacemaker or Defibrillator Implantation
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Cardiac Arrhythmias
Hemorrhage
Thromboembolism
Keywords: Atrial fibrillation
Mechanical heart valve
Stroke
Venous thromboembolism
Hemorrhage
Lead sponsor: McMaster University
Sponsor class: OTHER
First posted: 2014-03-21
Enrollment: 173
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Pocket hematoma
timeFrame: 1 month
Secondary outcomes:
measure: Major bleeding
timeFrame: 1 month
measure: Thromboembolism
timeFrame: 1 month
Other outcomes:
measure: Preoperative reversal with vitamin K
timeFrame: 1 day
Locations:
city: Hamilton
country: Canada
facility: Hamilton Health Sciences-General Hospital
state: Ontario
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare
state: Ontario
Study officials:
affiliation: McMaster University
name: Sam Schulman, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.2014.07.028. Epub 2014 Aug 1.