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

Phase 1

Terminated

• Conditions: Hypoprothrombinemia
• Interventions: Other: Warfarin adjustment using standard dosing; Other: Warfarin adjustment using the Fearon algorithm

• Registration Number: NCT02267408
• Lead Sponsor: McMaster University

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2014-10-14
• Study First Submitted QC: 2014-10-16
• Study First Posted: 2014-10-17
• Study Start: 2014-11
• Status Verified: 2016-03
• Primary Completion: 2017-02
• Study Completion: 2017-02-03
• Last Update Submitted: 2018-04-04
• Last Update Posted: 2018-04-06

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 42

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

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Exclusion Criteria

• Known poor compliance due to for example alcohol abuse or cognitive impairment
• Refusal to provide written informed consent

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard dosing	Warfarin adjustment using standard dosing	Warfarin adjustment using standard dosing
Fearon algorithm dosing	Warfarin adjustment using the Fearon algorithm	Warfarin adjustment using the Fearon algorithm

Primary Outcome Measures

Name	Time	Method
Improvement in TTR	6 months	The percent units of TTR during the 6 months will be compared with the percent units TTR in the previous year

Secondary Outcome Measures

Name	Time	Method
Proportion of patients with improvement in TTR	6 months	Proportion of included patients with TTR improvement of more than 5 percent units

Trial Locations

Locations (1)

Thrombosis Service, HHS-General Hospital; 🇨🇦 Hamilton, Ontario, Canada