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Low INR to Minimize Bleeding With Mechanical Valves Trial (LIMIT)

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ClinicalTrials.gov Identifier: NCT03636295
Recruitment Status : Recruiting
First Posted : August 17, 2018
Last Update Posted : November 13, 2019
Sponsor:
Information provided by (Responsible Party):
Emilie Belley-Cote, McMaster University

Brief Summary:
This study evaluates the use of a lower INR target (1.5 to 2.5) in patients with a mechanical heart valve in the aortic position. This study will inform physicians about whether a lower INR target will decrease the risk of bleeding or increase the risk of blood clot formation and stroke. These results have the potential to reduce the burden of bleeding in patients with a mechanical heart valve who require lifelong warfarin (Coumadin) treatment.

Condition or disease Intervention/treatment Phase
Bleeding Post-mechanical Valve Replacement Thromboembolism Post-mechanical Valve Replacement Drug: Warfarin Phase 3

Detailed Description:

Warfarin (Coumadin) is a blood thinner used to prevent blood clot formation in patients with mechanical heart valves. Blood clots can block blood flow to the brain, heart, or other parts of the body. Mechanical heart valves increases the risk of clot so patients with a mechanical heart valve must take warfarin to reduce their risk of stroke and other blood clot-related problems.

The degree to which warfarin 'works' varies from person to person, and so dosage is determined by measuring each person's response to the drug as an 'international normalized ratio' or INR. A patient with an INR over 1.0 has blood that takes longer to clot than average, and increasing INR values represent increasing time required for blood to clot. While an INR over 1.0 decreases clotting risk, it also increases bleeding risk. It is important to carefully balance these risks.

Specific INR targets have been recommended for patients with a mechanical heart valve, but these recommendations differ between scientific groups and are based on low quality evidence. Recent studies suggest that a lower INR target range than is currently recommended can be used safely. A laboratory study showed that warfarin effectively prevents blood clot formation on mechanical heart valves as long as the INR is 1.5 or above. Two moderately-sized clinical studies showed that an INR target range of 1.5-2.5 resulted in less bleeding than the usual higher target range without increasing blood clot formation or stroke in patients with a newer valve model. Whether we could use a lower INR target range for patients with a mechanical aortic valve remains controversial.

This study evaluates the use of a lower INR target (1.5 to 2.5) in patients with a mechanical heart valve in the aortic position. This study will inform physicians about whether a lower INR target will decrease the risk of bleeding or increase the risk of blood clot formation and stroke. These results have the potential to reduce the burden of bleeding in patients with a mechanical heart valve who require lifelong warfarin (Coumadin) treatment.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: A vanguard prospective, randomized, open-label, blinded end-point (PROBE) clinical trial.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Low INR to Minimize Bleeding With Mechanical Valves Trial - Vanguard
Actual Study Start Date : September 5, 2019
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : September 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Reduced INR Target
Warfarin therapy will be titrated to a target INR in the range of 1.5 to 2.5.
Drug: Warfarin
Participants in both arms will be on warfarin therapy post-mechanical valve replacement as is standard, but will have different INR target ranges.
Other Name: Coumadin

Active Comparator: Standard INR Target
Warfarin therapy will be titrated to a "standard of care" target INR range.
Drug: Warfarin
Participants in both arms will be on warfarin therapy post-mechanical valve replacement as is standard, but will have different INR target ranges.
Other Name: Coumadin




Primary Outcome Measures :
  1. Recruitment rate [ Time Frame: One year ]
    Recruitment of 200 subjects at 5 centres over 1 year


Secondary Outcome Measures :
  1. Valve patients consented/approached [ Time Frame: One year ]
    Percent of established prevalent (>1 year) valve patients consented/approached

  2. New valve patients consented/approached [ Time Frame: One year ]
    Percent of new valve (<1 year) patients consented/approached

  3. Crossover of INR target arms [ Time Frame: One year ]
    Percent of patients that crossover INR target arms

  4. Time in INR range [ Time Frame: One year ]
    Percentage of time spent in designated INR range over the course of follow-up

  5. Patients prescribed concomitant anti-platelet agent [ Time Frame: One year ]
    Percent of patients prescribed concomitant anti-platelet agent

  6. Patients at low risk vs. high risk (as per the PROACT definition) [ Time Frame: 1 year ]
    Percent of participants at low vs. high risk (as per the PROACT definition: those without 1 of the following conditions were considered in the low-risk group: chronic atrial fibrillation, left ventricular ejection fraction <30%, left atrial dimension >50 mm, spontaneous echocardiographic contrast in the left atrium, significant vascular disease, history of neurological events within 1 year, hypercoagulability, left or right ventricular aneurysm, and women receiving estrogen replacement therapy)



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

Inclusion criteria:

  • Age greater than 17 years
  • Is greater that 3 months post mechanical bileaflet aortic valve replacement
  • Written informed consent from either the patient or substitute decision maker

Exclusion criteria:

  • Has a second implanted mechanical valve (any position)
  • Lower boundary of planned INR range is less than 2.0
  • Pregnant or expecting to become pregnant during the study follow-up

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): NCT03636295


Contacts
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Contact: Emilie Belley-Côté, MD, MSc 905-527-4322 ext 40306 emilie.belley-cote@phri.ca
Contact: Richard Whitlock, MD, PhD 905-527-4322 ext 40306 richard.whitlock@phri.ca

Locations
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Canada, Ontario
Hamilton General Hospital Recruiting
Hamilton, Ontario, Canada, L8L 2X2
Contact: Emilie Belley-Cote, MD    905-527-4322 ext 40306    emilie.belley-cote@phri.ca   
Sponsors and Collaborators
McMaster University
Investigators
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Principal Investigator: Emilie Belley-Côté, MD, MSc McMaster University

Publications:
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Responsible Party: Emilie Belley-Cote, Principal Investigator, McMaster University
ClinicalTrials.gov Identifier: NCT03636295     History of Changes
Other Study ID Numbers: 5139
First Posted: August 17, 2018    Key Record Dates
Last Update Posted: November 13, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: We will establish a plan for the full-scale study but there is no plan to make IPD available to other researchers.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Emilie Belley-Cote, McMaster University:
Mechanical valve replacement
Vitamin K antagonist
INR targets
Bleeding
Thromboembolism
Additional relevant MeSH terms:
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Thromboembolism
Hemorrhage
Pathologic Processes
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Warfarin
Anticoagulants