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The Effect of Medication Timing on Anticoagulation Stability in Users of Warfarin: The "INRange" RCT

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02376803
First Posted: March 3, 2015
Last Update Posted: April 7, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Vancouver Coastal Health Research Institute
Information provided by (Responsible Party):
Scott Garrison, University of Alberta
  Purpose
Warfarin is an anticoagulant medication that is highly effective at preventing clotting disorders but which has a narrow therapeutic window. If warfarin is under effective patients are at risk of stroke, if it is over effective patients are at risk of bleeding complications. Physicians routinely and regularly measure a blood test (called the "INR") that determines the effectiveness of warfarin and have a range of test values (the "therapeutic range") in which they try to keep the patient. By convention warfarin is taken at dinnertime, however this is the same time of day that highly variable consumption of dietary vitamin K occurs (found largely in green leafy vegetables) and vitamin K alters the effectiveness of warfarin. Given vitamin K has a very short half-life (i.e. it is only active for a short period of time after it is ingested) it may make more sense to take warfarin in the morning (when very little vitamin K is ingested) to produce a more consistent drug effect. The purpose of this study is to determine whether switching current warfarin users from evening to morning dosing decreases time spent outside the therapeutic INR range.

Condition Intervention Phase
Atrial Fibrillation Thrombus Due to Heart Valve Prosthesis Deep Venous Thrombosis Thromboembolism DVT Drug: Warfarin Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Effect of Medication Timing on Anticoagulation Stability in Users of Warfarin: The "INRange" RCT

Resource links provided by NLM:


Further study details as provided by Scott Garrison, University of Alberta:

Primary Outcome Measures:
  • Percentage change in time spent OUTSIDE of therapeutic range [ Time Frame: 7 months ]
    Our primary outcome, percentage change in time spent OUTSIDE of therapeutic range is chosen because we believe this is a measure more likely to be shared by patients across a wide range of TTR (i.e. a patient with high baseline TTR and a patient with low baseline TTR may still share a similar % change in time outside of therapeutic range as a response to our intervention). This would not be true for change in TTR itself. It is also the time spent outside of range which contributes more directly to risk of thrombosis and hemorrhage and hence the change in this measure is more clinically meaningful than the change in TTR itself.


Secondary Outcome Measures:
  • Percentage change in time in therapeutic range (TTR) [ Time Frame: 7 months ]
  • Percentage of patients with TTR > 75% [ Time Frame: 7 months ]
    The percentage of patients with TTR > 75% provides the percentage of patients considered to have excellent control.

  • Percentage of patients with TTR < 60% [ Time Frame: 7 months ]
    The percentage of patients with TTR < 60% provides the percentage of patients for whom other anticoagulation strategies may be indicated.

  • Major warfarin related cardiovascular events [ Time Frame: 7 months ]
    Includes all-cause mortality, hospitalization for stroke, hospitalization for GI bleeding, and deep venous thrombosis / pulmonary embolism.

  • Maximum observed INR [ Time Frame: 7 months ]
    For those patients with at least one INR value above the therapeutic range, the maximum INR observed.

  • Minimum observed INR [ Time Frame: 7 months ]
    For those patients with at least one INR value below the therapeutic range, the minimum INR value observed.


Other Outcome Measures:
  • Major thromboembolic events [ Time Frame: 7 months ]
    Includes non-hemorrhagic stroke, deep vein thrombosis, pulmonary embolus and acute arterial occlusion

  • Major bleeding events [ Time Frame: 7 months ]
    Includes all bleeding events requiring hospitalization such as hemorrhagic stroke and GI bleeding

  • Allocation adherence [ Time Frame: 7 months ]
    Patient self-reports of adherence to their allocated intervention during telephone follow-up occurring at 1 week, 1 month and upon study completion


Enrollment: 217
Study Start Date: February 2015
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Morning warfarin ingestion
Patients switch from taking warfarin in the evening to taking warfarin in the morning.
Drug: Warfarin
Morning vs Evening administration
Other Name: Coumadin
Active Comparator: Evening warfarin ingestion
Patients continue taking warfarin in the evening as per their usual routine.
Drug: Warfarin
Morning vs Evening administration
Other Name: Coumadin

  Show Detailed Description

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Dinner or evening use of warfarin
  • ≥ 3 months of continuous warfarin use
  • Expectation of long-term warfarin use
  • Baseline INR data made available by family physician
  • Community dwelling

Exclusion Criteria:

  • Patient is palliative
  • Patient is unable to provide informed consent
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02376803


Locations
Canada, Alberta
University of Alberta
Edmonton, Alberta, Canada, T6G 2C8
Canada, British Columbia
Vancouver Coastal Health Research Institute
Vancouver, British Columbia, Canada, V5Z 1M9
Sponsors and Collaborators
University of Alberta
Vancouver Coastal Health Research Institute
Investigators
Principal Investigator: Scott R Garrison, MD PhD University of Alberta
  More Information

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Scott Garrison, Associate Professor, University of Alberta
ClinicalTrials.gov Identifier: NCT02376803     History of Changes
Other Study ID Numbers: INRange
First Submitted: February 25, 2015
First Posted: March 3, 2015
Last Update Posted: April 7, 2016
Last Verified: April 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Upon publication of all planned manuscripts stemming from this work, anonymized patient level trial data will be posted on www.PragmaticTrials.ca

Keywords provided by Scott Garrison, University of Alberta:
Randomized controlled trial
Warfarin
Time in therapeutic range
Bleeding
Thromboembolic
Hemorrhage
Anticoagulant
TTR
Chronobiology
Chronotherapeutic
Coumadin
INR
International normalized ratio
RCT

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