Reinitiation of Anticoagulation After Temporary Withdrawal of Vitamin K Antagonist (DOSIDO)
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.
Heart Valve Disease
Drug: Double dose
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study of Double Versus Single Reinitiation Dose of Warfarin After Interruption for Surgery|
- Proportion of patients with INR back in therapeutic range Day 5 or Day 10 [ Time Frame: Day 5-10 ] [ Designated as safety issue: No ]Proportion of patients with INR 2.0-3.0 on Day 5 or Day 10 (day of invasive procedure defined as Day 1)
- Thromboembolic events [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]Objectively verified arterial or venous thromboembolic events
- Major bleeding events [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]Defined by the ISTH criteria of 2010
- Minor bleeding events [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]Any bleeding requiring medical attention but not fulfilling the criteria of Major bleeding
- Laboratory parameters of hypercoagulability [ Time Frame: 10 days ] [ Designated as safety issue: Yes ]Quantitative D-dimer and Thrombin Generation performed in a subset at day of procedure, day 5 and 10 to identify abnormal rise.
|Study Start Date:||April 2011|
|Estimated Study Completion Date:||April 2013|
|Estimated Primary Completion Date:||December 2012 (Final data collection date for primary outcome measure)|
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 Name: Loading dose
No Intervention: Usual maintenance dose
Usual maintenance dose from Day 1, i.e. no postoperative loading dose.
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.
|Contact: Sam Schulman, MD||1-905-5270271 ext firstname.lastname@example.org|
|Thrombosis Service, HHS- General Hospital||Recruiting|
|Hamilton, Ontario, Canada, L8L 2X2|
|Contact: Sam Schulman, MD, PhD 1-905-5270271 ext 44810 email@example.com|
|Contact: Jennifer Delaney, RN 1-905-5270271 ext 44510 firstname.lastname@example.org|
|Sub-Investigator: Hun-Gyu Hwang, MD|
|Principal Investigator:||Sam Schulman, MD, PhD||McMaster University|