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

NCT02094157 | Terminated Phase 3

• 1 other identifier: PB 20080717
• Study Type: interventional
• Target: 173
• Locations: 1 country
• Sites: 2

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.

Conditions

Cardiac Arrhythmias; Hemorrhage; Thromboembolism

Keywords

Atrial fibrillation; Mechanical heart valve; Stroke; Venous thromboembolism; Hemorrhage

Outcome Measures

Primary Outcomes (1)

• Pocket hematoma

  Pocket hematoma is defined as palpable swelling of the pacemaker or defibrillator pocket exceeding the size of the generator.

  1 month

Secondary Outcomes (2)

• Major bleeding

  1 month

• Thromboembolism

  1 month

Other Outcomes (1)

• Preoperative reversal with vitamin K

  1 day

Study Arms (2)

Bridged regimen

ACTIVE COMPARATOR

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

Tapered warfarin regimen

EXPERIMENTAL

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

Interventions

Tapered warfarin regimen DRUG

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

Also known as: Half dose warfarin

Tapered warfarin regimen

Bridged regimen Low-molecular-weight heparin DRUG

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

Also known as: Low-molecular-weight heparin

Bridged regimen

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• McMaster University: lead

Study Sites (2)

Hamilton Health Sciences-General Hospital

Hamilton, Ontario, L8L 2X2, Canada

Location

St. Joseph's Healthcare

Hamilton, Ontario, L8N 4A6, Canada

Location

Related 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.2014.07.028. Epub 2014 Aug 1.

  PMID: 25127655 RESULT

MeSH Terms

Conditions

Arrhythmias, Cardiac; Hemorrhage; Thromboembolism; Atrial Fibrillation; Stroke; Venous Thromboembolism

Interventions

Heparin, Low-Molecular-Weight

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Embolism and Thrombosis; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• Sam Schulman, MD, PhD

  McMaster University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2014
• First Posted: March 21, 2014
• Study Start: December 1, 2007
• Primary Completion: November 1, 2013
• Study Completion: March 1, 2014
• Last Updated: April 5, 2016

Record last verified: 2016-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2)