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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sam Schulman, McMaster University
ClinicalTrials.gov Identifier:
NCT00814177
First received: December 23, 2008
Last updated: July 24, 2012
Last verified: July 2012
  Purpose

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.


Condition Intervention Phase
Atrial Fibrillation
Venous Thromboembolism
Ischemic Stroke
Myocardial Infarction
Drug: warfarin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Management of Prothrombin Times Outside the Therapeutic Range in Patients on Warfarin and With Otherwise Stable Levels

Resource links provided by NLM:


Further study details as provided by McMaster University:

Primary Outcome Measures:
  • Number of Patients With Prothrombin Time Results Within the Therapeutic Range After 2 Weeks [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
    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.


Enrollment: 160
Study Start Date: July 2006
Study Completion Date: April 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Coumadin
Active Comparator: Change
Intervention Drug Warfarin One dose increased if subtherapeutic level; one dose deleted or reduced if supratherapeutic level
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 Name: Coumadin

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00814177

Locations
Canada, Ontario
Thrombosis Service, HHS-General Hospital
Hamilton, Ontario, Canada, L8L 2X2
Sponsors and Collaborators
Hamilton Health Sciences Corporation
Investigators
Principal Investigator: Sam Schulman, MD, PhD McMaster University
  More Information

Publications:
Responsible Party: Sam Schulman, Professor, MD, McMaster University
ClinicalTrials.gov Identifier: NCT00814177     History of Changes
Other Study ID Numbers: HRC060425
Study First Received: December 23, 2008
Results First Received: October 7, 2009
Last Updated: July 24, 2012
Health Authority: Canada: Ethics Review Committee

Keywords provided by McMaster University:
warfarin
dosing
prothrombin time
Heart valve prosthesis

Additional relevant MeSH terms:
Infarction
Atrial Fibrillation
Myocardial Infarction
Thromboembolism
Venous Thromboembolism
Venous Thrombosis
Ischemia
Pathologic Processes
Necrosis
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Myocardial Ischemia
Vascular Diseases
Embolism and Thrombosis
Thrombosis
Warfarin
Thrombin
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Hemostatics
Coagulants

ClinicalTrials.gov processed this record on October 02, 2014