Reinitiation of Anticoagulation After Temporary Withdrawal of Vitamin K Antagonist

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase II Study of Double Versus Single Reinitiation Dose of Warfarin After Interruption for Surgery

Conditions
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Atrial Fibrillation, Venous Thromboembolism, Heart Valve Disease, Surgery

Intervention / Treatment
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* Drug: Double dose


Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Double dose<br>Re-initiation with warfarin at twice the usual maintenance dose the first 2 days, then maintenance dose. | Drug: Double dose<br>* For each individual the dose on Day 1 and Day 2 will be twice the one normally taken<br>* Other names: Loading dose;|
| No Intervention: Usual maintenance dose<br>Usual maintenance dose from Day 1, i.e. no postoperative loading dose. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with INR back in therapeutic range Day 5 or Day 10 | Proportion of patients with INR 2.0-3.0 on Day 5 or Day 10 (day of invasive procedure defined as Day 1) | Day 5-10 | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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warfarin, surgery, management, thromboembolism, bleeding