DOSIDO: Reinitiation of Anticoagulation After Temporary Withdrawal of Vitamin K Antagonist

Sponsor

McMaster University (Other)

Overall Status

Completed

CT.gov ID

NCT01348074

Collaborator

(none)

104

Enrollment

Location

Arms

Duration (Months)

3.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation Venous Thromboembolism Heart Valve Disease Surgery	Drug: Double dose	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

104 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Apr 1, 2011

Actual Primary Completion Date :

Dec 1, 2013

Actual Study Completion Date :

Dec 1, 2013

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Double dose

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

Drug: Double dose

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

Other Names:

Loading dose

No Intervention: Usual maintenance dose

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

Outcome Measures

Primary Outcome Measures

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

Thromboembolic events [30 days]
Objectively verified arterial or venous thromboembolic events
Major bleeding events [30 days]
Defined by the ISTH criteria of 2010
Minor bleeding events [30 days]
Any bleeding requiring medical attention but not fulfilling the criteria of Major bleeding
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.