Prothrombin Times Outside the Therapeutic Range in Otherwise Stable Patients

NCT ID: NCT00814177

Last Updated: 2012-08-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-07-31
• Study Completion Date: 2009-04-30

Brief Summary

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.

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.

Conditions

Atrial Fibrillation; Venous Thromboembolism; Ischemic Stroke; Myocardial Infarction

Keywords

warfarin; dosing; prothrombin time; Heart valve prosthesis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

No change

Intervention Drug warfarin no change in the dose is performed

Group Type: EXPERIMENTAL

warfarin

Intervention Type: DRUG

No change: Continue without any change in spite of prothrombin time outside the therapeutic range.

Change

Intervention Drug Warfarin One dose increased if subtherapeutic level; one dose deleted or reduced if supratherapeutic level

Group Type: ACTIVE_COMPARATOR

warfarin

Intervention Type: DRUG

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.

Interventions

warfarin

No change: Continue without any change in spite of prothrombin time outside the therapeutic range.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Coumadin; Coumadin

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hamilton Health Sciences Corporation

OTHER

Sponsor Role: lead

Responsible Party

Sam Schulman

Professor, MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sam Schulman, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

McMaster University

Locations

Thrombosis Service, HHS-General Hospital

Hamilton, Ontario, Canada

Countries

Canada

References

Schulman S, Melinyshyn A, Ennis D, Rudd-Scott L. Single-dose adjustment versus no adjustment of warfarin in stably anticoagulated patients with an occasional international normalized ratio (INR) out of range. Thromb Res. 2010 May;125(5):393-7. doi: 10.1016/j.thromres.2009.07.006. Epub 2009 Jul 29.

Reference Type: RESULT

PMID: 19640572 (View on PubMed)

Other Identifiers

HRC060425

Identifier Type: -

Identifier Source: org_study_id