Prothrombin Times Outside the Therapeutic Range in Otherwise Stable Patients (FORESPEAK-0)

July 24, 2012 updated by: Sam Schulman, Hamilton Health Sciences Corporation

Management of Prothrombin Times Outside the Therapeutic Range in Patients on Warfarin and With Otherwise Stable Levels

Warfarin is very effective for the prevention of blood clots (thrombosis). A test of coagulation, the prothrombin time (PT) is used to monitor the effect. The PT response to warfarin can fluctuate as a result of interactions with a large number of other drugs, food or herbal agents as well as for no apparent reason. Thus, frequent monitoring of the PT and dose adjustments according to the results are required. One third of our patients remain on the same maintenance dose over 6 months. However, also these patients sometimes have a PT result moderately outside the therapeutic range without any obvious explanation. Too short PTs may be due to missed dose(s) or more dark green vegetables in the diet. Too long PTs may be due to a course of antibiotic therapy or less dark green vegetables. Laboratory errors may also occur and can cause deviations in any direction. Most likely, unnoticed fluctuations in the PT occur as well between the time points of monitoring.

There are no guidelines on how to manage the treatment in this situation but there are some typical "behaviours".

Behavior A: Some physicians simply let the patient continue with the same dose. "It is extremely unlikely that the very temporary dose adjustment has any effect on the PT result 4 weeks later and this is a "cosmetic procedure"." Behavior B: Others recommend the patients to take ½ - 1 additional dose in case of short PT and to skip a dose or take half dose in case of long PT, and thereafter to continue with the usual dose. "The investigators need to quickly correct the temporary aberration in order to avoid thrombotic or bleeding complications the next few days.

This may seem like an issue of no importance. The investigators are however performing a series of studies to evaluate if these stable patients can be managed with blood tests less often than every 4 weeks. For that purpose it is important to know how often and why aberrant results occur, the implication and to what extent they can be ignored.

The investigators hypothesis is that in patients with very stable PT-results and unchanged dose for 3 months, should continue with exactly the same maintenance dose, even when the result unexpectedly is slightly above or below the therapeutic range. The investigators believe that most of these occasional PT-results outside the therapeutic range are due to laboratory errors, perhaps missed doses by the patient or temporary change in diet or medications.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Setting:

Thrombosis Service at HHS - General Hospital. This center monitors the warfarin treatment for 1300 patients in the region. These patient regularly go to a laboratory where they live. Test results (INR-results) are faxed to the Thrombosis Service, which calls the patient the same day to inform them of the results, how to continue dosing the warfarin and when to go for the following blood test.

Study Type

Interventional

Enrollment (Actual)

160

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  1. Patients on long-term warfarin (for prophylaxis of arterial embolism in patients with atrial fibrillation or mechanical heart valve replacement, or secondary prophylaxis after VTE) with a target INR of 2.0-3.0 or 2.5-3.5,
  2. Anticoagulant therapy managed by the clinic (HHS - General Hospital) for at least 3 months prior to enrolment, and
  3. Maintenance dose of warfarin unchanged for the previous 3 months or longer.
  4. The INR result is outside the therapeutic range as follows:

For those with target 2.0-3.0: Either an INR of 1.5-1.9 or an INR of 3.1-4.4. For those with target 2.5-3.5: Either an INR of 1.5-2.4 or an INR of 3.6-4.4.

Exclusion Criteria:

  1. Age <18 years,
  2. Long-term (>1 week) change in any other medication
  3. Long-term (>1 week) change in diet, especially regarding green vegetables.
  4. Attending physician believes the patient is not suitable for the study (e.g. psychiatric disorder, history of non-compliance),
  5. Failure to obtain telephone consent.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: No change
Intervention Drug warfarin no change in the dose is performed
Drug: warfarin
No change: Continue without any change in spite of prothrombin time outside the therapeutic range.
Other Names:
  • Coumadin
Drug: warfarin
Change: Increase one dose in case prothrombin time is below the therapeutic range; delete or reduce one dose in case prothrombin time is above the therapeutic range.
Other Names:
  • Coumadin
Active Comparator: Change
Intervention Drug Warfarin One dose increased if subtherapeutic level; one dose deleted or reduced if supratherapeutic level
Drug: warfarin
No change: Continue without any change in spite of prothrombin time outside the therapeutic range.
Other Names:
  • Coumadin
Drug: warfarin
Change: Increase one dose in case prothrombin time is below the therapeutic range; delete or reduce one dose in case prothrombin time is above the therapeutic range.
Other Names:
  • Coumadin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Patients With Prothrombin Time Results Within the Therapeutic Range After 2 Weeks
Time Frame: 2 weeks
The number of patients with "follow-up INRs" within the therapeutic range was compared for patients with a single dose skipped/reduced/added versus patients with no change of dose.
2 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hamilton Health Sciences Corporation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2006

Primary Completion (Actual)

January 1, 2009

Study Completion (Actual)

April 1, 2009

Study Registration Dates

First Submitted

December 23, 2008

First Submitted That Met QC Criteria

December 23, 2008

First Posted (Estimate)

December 24, 2008

Study Record Updates

Last Update Posted (Estimate)

August 1, 2012

Last Update Submitted That Met QC Criteria

July 24, 2012

Last Verified

July 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HRC060425

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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