Reinitiation of Anticoagulation After Temporary Withdrawal of Vitamin K Antagonist

Phase 2

Completed

• Conditions: Venous Thromboembolism; Surgery; Atrial Fibrillation; Heart Valve Disease
• Interventions: Drug: Double dose

• Registration Number: NCT01348074
• Lead Sponsor: McMaster University

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.

Study Timeline

• Study Start: 2011-04
• Study First Submitted: 2011-05-03
• Study First Submitted QC: 2011-05-04
• Study First Posted: 2011-05-05
• Primary Completion: 2013-12
• Study Completion: 2013-12
• Status Verified: 2016-04
• Last Update Submitted: 2016-04-01
• Last Update Posted: 2016-04-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 104

Inclusion Criteria

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

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Exclusion Criteria

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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Proportion of patients with INR back in therapeutic range Day 5 or Day 10	Day 5-10	Proportion of patients with INR 2.0-3.0 on Day 5 or Day 10 (day of invasive procedure defined as Day 1)

Secondary Outcome Measures

Name	Time	Method
Laboratory parameters of hypercoagulability	10 days	Quantitative D-dimer and Thrombin Generation performed in a subset at day of procedure, day 5 and 10 to identify abnormal rise.
Major bleeding events	30 days	Defined by the ISTH criteria of 2010
Thromboembolic events	30 days	Objectively verified arterial or venous thromboembolic events
Minor bleeding events	30 days	Any bleeding requiring medical attention but not fulfilling the criteria of Major bleeding

Trial Locations

Locations (1)

Thrombosis Service, HHS- General Hospital; 🇨🇦 Hamilton, Ontario, Canada