Prothrombin Times Outside the Therapeutic Range in Otherwise Stable Patients

NCT00814177 | Completed Phase 2 Results DMC

• 1 other identifier: HRC060425
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

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.

Conditions

Atrial Fibrillation; Venous Thromboembolism; Ischemic Stroke; Myocardial Infarction

Keywords

warfarin; dosing; prothrombin time; Heart valve prosthesis

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Prothrombin Time Results Within the Therapeutic Range After 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

Study Arms (2)

No change

EXPERIMENTAL

Intervention Drug warfarin no change in the dose is performed

Drug: warfarin

Change

ACTIVE COMPARATOR

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

Drug: warfarin

Interventions

warfarin DRUG

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

Also known as: Coumadin

No change

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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,
• Anticoagulant therapy managed by the clinic (HHS - General Hospital) for at least 3 months prior to enrolment, and
• Maintenance dose of warfarin unchanged for the previous 3 months or longer.
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Hamilton Health Sciences Corporation: lead

Study Sites (1)

Thrombosis Service, HHS-General Hospital

Hamilton, Ontario, L8L 2X2, Canada

Location

Related Publications (1)

• 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.

  PMID: 19640572 RESULT

MeSH Terms

Conditions

Atrial Fibrillation; Venous Thromboembolism; Ischemic Stroke; Myocardial Infarction

Interventions

Warfarin

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Myocardial Ischemia; Infarction; Ischemia; Necrosis

Intervention Hierarchy (Ancestors)

4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Sam Schulman, MD
• Organization: McMaster University

schulms@mcmaster.ca

1-905-5270271

Study Officials

• Sam Schulman, MD, PhD

  McMaster University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, MD

Study Record Dates

• First Submitted: December 23, 2008
• First Posted: December 24, 2008
• Study Start: July 1, 2006
• Primary Completion: January 1, 2009
• Study Completion: April 1, 2009
• Last Updated: August 1, 2012
• Results First Posted: November 25, 2009

Record last verified: 2012-07

Locations

CA (1)