HypoprothrombinemiaPhase 1/2NCT02267408
Randomized Controlled Feasibility Trial of the Fearon Algorithm to Improve Management of Unstable Warfarin
A Phase 1/2 study testing Warfarin adjustment using the Fearon algorithm and Warfarin adjustment using standard dosing in people with Hypoprothrombinemia, run by McMaster University at 1 site in Canada.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hypoprothrombinemia
- What is being tested?
- Warfarin adjustment using the Fearon algorithm and Warfarin adjustment using standard dosing
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteCanada
- Study dates
- Nov 2014to 3 Feb 2017
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Known poor compliance due to for example alcohol abuse or cognitive impairment
- Refusal to provide written informed consent
Trial locations and contacts
1 site in 1 country.
Canada1 site
Thrombosis Service, HHS-General Hospital
Hamilton, Ontario, L8L 2X2
About this study
Official title: 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.
Read the 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.
- Conditions
- Hypoprothrombinemia
- Being tested
- Warfarin adjustment using the Fearon algorithm, Warfarin adjustment using standard dosing
- Keywords
- Heart valve prosthesis, Anticoagulation, Warfarin
- Medical subject headings
- Hypoprothrombinemias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Warfarin adjustment using the Fearon algorithmOther
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.
Warfarin adjustment using standard dosingOther
Patients will receive warfarin dosing instructions from a trained nurse using fixed nomograms and computer-based dosing suggestion.
| Study group | Role | What they receive |
|---|---|---|
| Fearon algorithm dosing | Experimental | Warfarin adjustment using the Fearon algorithm Receives: Other: Warfarin adjustment using the Fearon algorithm |
| Standard dosing | Active comparator | Warfarin adjustment using standard dosing Receives: Other: Warfarin adjustment using standard dosing |
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvement in TTR
The percent units of TTR during the 6 months will be compared with the percent units TTR in the previous year
Measured: 6 months
Secondary outcomes (1)
Proportion of patients with improvement in TTR
Proportion of included patients with TTR improvement of more than 5 percent units
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2014 (estimated)
- Study startNov 2014
- Primary completionFeb 2017
- Study completion3 Feb 2017
Why it stopped: Terminated by sponsor
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HypoprothrombinemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Dosing of warfarin according to the Fearon algorithm or routine during 6 months for patients with unstable INRs
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- McMaster University
- Sponsor type
- University, hospital or other
- Collaborators
- Epitome Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Sam Schulman, MD, PhD, Principal investigator, McMaster University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02267408
- Sponsor's protocol ID
- Fearon pilot RCT, version 03
- Status last verified
- Mar 2016
- First submitted
- 14 Oct 2014
- Last updated
- 6 Apr 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-site, Randomized Controlled Feasibility Trial of the Fearon Algorithm to Improve Management of Patients With Unstable Warfarin Effect.
- ClinicalTrials.gov ID
- NCT02267408
- Acronym / sponsor ID
- Fearon pilot RCT, version 03
- Conditions
- Hypoprothrombinemia
- Keywords
- Heart valve prosthesis, Anticoagulation, Warfarin
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated by sponsor
- Enrolment
- 42 participants (actual)
- Lead sponsor
- McMaster UniversityUniversity, hospital or other
- Collaborators
- Epitome Pharmaceuticals
- Study start
- Nov 2014
- Primary completion
- Feb 2017 (actual)
- Study completion
- 3 Feb 2017 (actual)
- First posted
- 17 Oct 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Dosing of warfarin according to the Fearon algorithm or routine during 6 months for patients with unstable INRs
| Arm | Type | Receives |
|---|---|---|
| Fearon algorithm dosing | Experimental | Other: Warfarin adjustment using the Fearon algorithmWarfarin adjustment using the Fearon algorithm |
| Standard dosing | Active comparator | Other: Warfarin adjustment using standard dosingWarfarin adjustment using standard dosing |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (2 listed)
- Known poor compliance due to for example alcohol abuse or cognitive impairment
- Refusal to provide written informed consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Warfarin adjustment using the Fearon algorithmAll 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. | Other | Fearon algorithm dosing |
| Warfarin adjustment using standard dosingPatients will receive warfarin dosing instructions from a trained nurse using fixed nomograms and computer-based dosing suggestion. | Other | Standard dosing |
Primary outcome
Improvement in TTR
Time frame: 6 months
The percent units of TTR during the 6 months will be compared with the percent units TTR in the previous year
1 secondary outcome
Proportion of patients with improvement in TTR
Time frame: 6 months
Results and safety
The study was stopped early (reason given: Terminated by sponsor). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2018.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sam Schulman, MD, PhD principal investigator
McMaster University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Warfarin adjustment using the Fearon algorithm and Warfarin adjustment using standard dosing in people with Hypoprothrombinemia, run by McMaster University at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 6 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Terminated by sponsor). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Improvement in TTR (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2018.