Reinitiation of Anticoagulation After Temporary Withdrawal of Vitamin K Antagonist

Atrial Fibrillation Clinical Trial

— DOSIDO  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01348074
• Other study ID #: HGH20090520
• Status: Completed
• Phase: Phase 2
• First received: May 3, 2011
• Last updated: April 1, 2016
• Start date: April 2011
• Est. completion date: December 2013

Study information

• Verified date: April 2016
• Source: McMaster University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 104
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Atrial Fibrillation
• Heart Valve Disease
• Heart Valve Diseases
• Surgery
• Thromboembolism
• Venous Thromboembolism

Intervention

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

Locations

Country	Name	City	State
Canada	Thrombosis Service, HHS- General Hospital	Hamilton	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
McMaster University

Country where clinical trial is conducted

Canada, 

References & Publications (2)

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. — View 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Thromboembolic events	Objectively verified arterial or venous thromboembolic events	30 days	Yes
Secondary	Major bleeding events	Defined by the ISTH criteria of 2010	30 days	Yes
Secondary	Minor bleeding events	Any bleeding requiring medical attention but not fulfilling the criteria of Major bleeding	30 days	Yes
Secondary	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	Yes

External Links

•   Published article on this study