Reinitiation of Anticoagulation After Temporary Withdrawal of Vitamin K Antagonist

NCT ID: NCT01348074

Last Updated: 2016-04-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 104 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-04-30
• Study Completion Date: 2013-12-31

Brief Summary

It is not known how to best restart warfarin after temporary withdrawal. Participants will be randomized to two groups. Group 1 will restart warfarin at their usual maintenance dose, group 2 will restart warfarin at double their maintenance dose for two days followed by their usual maintenance dose. The main outcome parameter will be the number of patients who are back in therapeutic INR (international normalized ratio) range 4, and 9 days after restarting anticoagulation with warfarin. Thromboembolic and/or bleeding events will be recorded as additional parameters. These data will be collected by a standardized telephone interview at 1 month. In addition, the investigators will evaluate a possible prothrombotic state by measuring the potential of thrombin generation and D-dimers in the subset of patients visiting HHS-General Hospital for their INR tests.

Detailed Description

We will investigate if it is feasible to use double maintenance dose for the first two administrations of vitamin K antagonists when these drugs were temporarily interrupted and thus keep the time of an increased risk of thromboembolism and duration of "bridging" at a minimum. The control group will consist of patients who resume vitamin K antagonists at their usual maintenance dose. The aim of the study is to establish how to best restart anticoagulation with vitamin K antagonists after temporal withdrawal of these drugs. The main outcome parameter will be the proportion of patients who are back to a therapeutic international normalized ratio (INR) ratio at certain days after restarting vitamin K antagonists. Two additional parameters will be evaluated: Firstly, bleeding and thromboembolic complications will be reported and secondly, a possible prothrombotic state, measured as an elevation of D-dimer, at the initiation of anticoagulation will be evaluated.

Conditions

Atrial Fibrillation; Venous Thromboembolism; Heart Valve Disease; Surgery

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Double dose

Re-initiation with warfarin at twice the usual maintenance dose the first 2 days, then maintenance dose.

Group Type: EXPERIMENTAL

Double dose

Intervention Type: DRUG

For each individual the dose on Day 1 and Day 2 will be twice the one normally taken

Usual maintenance dose

Usual maintenance dose from Day 1, i.e. no postoperative loading dose.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Double dose

For each individual the dose on Day 1 and Day 2 will be twice the one normally taken

Intervention Type: DRUG

Other Intervention Names

Loading dose

Eligibility Criteria

Inclusion Criteria

• Current treatment with warfarin
• Need for temporary interruption for invasive procedure or surgery

Exclusion Criteria

• Need for post-operative hospitalization more than one day
• Participation in another clinical trial
• No consent given

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

McMaster University

OTHER

Sponsor Role: lead

Responsible Party

Sam Schulman

Prof.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sam Schulman, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

McMaster University

Locations

Thrombosis Service, HHS- General Hospital

Hamilton, Ontario, Canada

Countries

Canada

References

Schulman S, El Bouazzaoui B, Eikelboom JW, Zondag M. Clinical factors influencing the sensitivity to warfarin when restarted after surgery. J Intern Med. 2008 Apr;263(4):412-9. doi: 10.1111/j.1365-2796.2007.01913.x. Epub 2008 Jan 16.

Reference Type: BACKGROUND

PMID: 18205763 (View on PubMed)

Schulman S, Hwang HG, Eikelboom JW, Kearon C, Pai M, Delaney J. Loading dose vs. maintenance dose of warfarin for reinitiation after invasive procedures: a randomized trial. J Thromb Haemost. 2014 Aug;12(8):1254-9. doi: 10.1111/jth.12613. Epub 2014 Jun 25.

Reference Type: RESULT

PMID: 24837794 (View on PubMed)

Related Links

http://onlinelibrary.wiley.com/doi/10.1111/jth.12613/abstract

Published article on this study

Other Identifiers

HGH20090520

Identifier Type: -

Identifier Source: org_study_id