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

NCT ID: NCT02094157

Last Updated: 2016-04-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 173 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-12-31
• Study Completion Date: 2014-03-31

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.

Conditions

Cardiac Arrhythmias; Hemorrhage; Thromboembolism

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Bridged regimen Low-molecular-weight heparin

Intervention Type: DRUG

This intervention is assigned to the active control arm - Bridged regimen

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.

Group Type: EXPERIMENTAL

Tapered warfarin regimen

Intervention Type: DRUG

This intervention is assigned to the experimental arm - Tapered warfarin regimen

Interventions

Tapered warfarin regimen

This intervention is assigned to the experimental arm - Tapered warfarin regimen

Intervention Type: DRUG

Bridged regimen Low-molecular-weight heparin

This intervention is assigned to the active control arm - Bridged regimen

Intervention Type: DRUG

Other Intervention Names

Half dose warfarin; Low-molecular-weight heparin

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

McMaster University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sam Schulman, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

McMaster University

Locations

Hamilton Health Sciences-General Hospital

Hamilton, Ontario, Canada

St. Joseph's Healthcare

Hamilton, Ontario, Canada

Countries

Canada

References

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.

Reference Type: RESULT

PMID: 25127655 (View on PubMed)

Other Identifiers

PB 20080717

Identifier Type: -

Identifier Source: org_study_id