Reinitiation of Anticoagulation After Temporary Withdrawal of Vitamin K Antagonist (DOSIDO)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sam Schulman, McMaster University
ClinicalTrials.gov Identifier:
NCT01348074
First received: May 3, 2011
Last updated: January 14, 2014
Last verified: January 2014
  Purpose

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 Intervention Phase
Atrial Fibrillation
Venous Thromboembolism
Heart Valve Disease
Surgery
Drug: Double dose
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by McMaster University:

Primary Outcome Measures:
  • 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)


Secondary Outcome Measures:
  • 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.


Enrollment: 104
Study Start Date: April 2011
Study Completion Date: December 2013
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01348074

Locations
Canada, Ontario
Thrombosis Service, HHS- General Hospital
Hamilton, Ontario, Canada, L8L 2X2
Sponsors and Collaborators
McMaster University
Investigators
Principal Investigator: Sam Schulman, MD, PhD McMaster University
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Sam Schulman, Prof., McMaster University
ClinicalTrials.gov Identifier: NCT01348074     History of Changes
Other Study ID Numbers: HGH20090520
Study First Received: May 3, 2011
Last Updated: January 14, 2014
Health Authority: Canada: Health Canada

Keywords provided by McMaster University:
warfarin
surgery
management
thromboembolism
bleeding

Additional relevant MeSH terms:
Atrial Fibrillation
Thromboembolism
Venous Thromboembolism
Venous Thrombosis
Heart Valve Diseases
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Embolism and Thrombosis
Vascular Diseases
Thrombosis

ClinicalTrials.gov processed this record on September 30, 2014