Randomized Controlled Feasibility Trial of the Fearon Algorithm to Improve Management of Unstable Warfarin

Study Overview
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Brief Summary
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Patients on warfarin but with unstable international normalized ratio (INR) will be recruited to a randomized trial comparing dosing based on an algorithm (Fearon algorithm, named after the mathematician Michael Fearon), which uses historical data to estimate patients' sensitivity to warfarin and to dose changes as well as the lag time until a dose adjustment takes effect, or to the investigators standard management Main outcome is improvement in time in therapeutic range.

Detailed Description
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Patients with very variable INRs resulting in a low proportion of time in therapeutic range (TTR) have a higher risk of both bleeding complications and thromboembolic events. A good TTR is generally considered to be over 60% and excellent TTR is above 72% of time in range. The investigators will recruit patients with a TTR below 50%. The Fearon algorithm provides a more thorough understanding of the individual responses to changes in warfarin dose and with a personalized nomogram for dose adjustments and timing of laboratory tests the investigators have an opportunity to improve the TTR and on a larger scale to reduce clinically important adverse events. Before embarking on a large randomized trial with this revised Fearon algorithm-derived nomogram this pilot study with a randomized, open-label design will be performed to demonstrate proof of principle.

Official Title
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A Single-site, Randomized Controlled Feasibility Trial of the Fearon Algorithm to Improve Management of Patients With Unstable Warfarin Effect.

Conditions
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Hypoprothrombinemia

Intervention / Treatment
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* Other: Warfarin adjustment using the Fearon algorithm
* Other: Warfarin adjustment using standard dosing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with mechanical heart valve prosthesis managed for the warfarin therapy by the Thrombosis Service at HHS-General Hospital. Treated with warfarin for at least 1 year. Therapeutic INR range 2.0-3.0 or 2.5-3.5. TTR in the lowest quartile Exclusion Criteria: Known poor compliance due to for example alcohol abuse or cognitive impairment Refusal to provide written informed consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Dosing of warfarin according to the Fearon algorithm or routine during 6 months for patients with unstable INRs
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fearon algorithm dosing<br>Warfarin adjustment using the Fearon algorithm | Other: Warfarin adjustment using the Fearon algorithm<br>* All available historical data will be used to calculate with the Fearon algorithm the individual sensitivity to warfarin and to dose changes as well as lag time until a dose adjustment reaches full effect. Based on this a personal dosing nomogram will be developed and provided to the investigator and to the patients. This nomogram will be used during 6 month but override is possible if the investigator feels that the suggestion from the nomogram is unsafe.<br>|
| Active Comparator: Standard dosing<br>Warfarin adjustment using standard dosing | Other: Warfarin adjustment using standard dosing<br>* Patients will receive warfarin dosing instructions from a trained nurse using fixed nomograms and computer-based dosing suggestion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in TTR | The percent units of TTR during the 6 months will be compared with the percent units TTR in the previous year | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with improvement in TTR | Proportion of included patients with TTR improvement of more than 5 percent units | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart valve prosthesis, Anticoagulation, Warfarin