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

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

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.

Study Overview

• Status: Terminated
• Conditions: Hypoprothrombinemia
• Intervention / Treatment: Other: Warfarin adjustment using the Fearon algorithm; Other: Warfarin adjustment using standard dosing

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 Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Thrombosis Service, HHS-General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fearon algorithm dosing; Warfarin adjustment using the Fearon algorithm	Other: Warfarin adjustment using the Fearon algorithm; 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.
Active Comparator: Standard dosing; Warfarin adjustment using standard dosing	Other: Warfarin adjustment using standard dosing; Patients will receive warfarin dosing instructions from a trained nurse using fixed nomograms and computer-based dosing suggestion.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: McMaster University
• Collaborators: Epitome Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Actual): February 1, 2017
• Study Completion (Actual): February 3, 2017

Study Registration Dates

• First Submitted: October 14, 2014
• First Submitted That Met QC Criteria: October 16, 2014
• First Posted (Estimate): October 17, 2014

Study Record Updates

• Last Update Posted (Actual): April 6, 2018
• Last Update Submitted That Met QC Criteria: April 4, 2018
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: Anticoagulation; Warfarin; Heart valve prosthesis
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Hypoprothrombinemias; Anticoagulants; Warfarin
• Other Study ID Numbers: Fearon pilot RCT, version 03