Clinical trial NCT01348074: Reinitiation of Anticoagulation After Temporary Withdrawal of Vitamin K Antagonist
Official title: Phase II Study of Double Versus Single Reinitiation Dose of Warfarin After Interruption for Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Atrial Fibrillation
Venous Thromboembolism
Heart Valve Disease
Surgery
Keywords: warfarin
surgery
management
thromboembolism
bleeding
Lead sponsor: McMaster University
Sponsor class: OTHER
First posted: 2011-05-05
Enrollment: 104
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Proportion of patients with INR back in therapeutic range Day 5 or Day 10
timeFrame: Day 5-10
Secondary outcomes:
measure: Thromboembolic events
timeFrame: 30 days
measure: Major bleeding events
timeFrame: 30 days
measure: Minor bleeding events
timeFrame: 30 days
measure: Laboratory parameters of hypercoagulability
timeFrame: 10 days
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: Thrombosis Service, HHS- General Hospital
state: Ontario
Study officials:
affiliation: McMaster University
name: Sam Schulman, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.