Clinical trial NCT01654042: Prolongation of the Interval Between Prothrombin Time Tests in Stable Patients II
Official title: Prolongation of the Interval Between Prothrombin Time Tests in Stable Patients II (the PRINT II Study): a Randomized Controlled, Non-inferiority Trial Comparing 4-weekly With 12-weekly Testing and Dose-assessment
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Atrial Fibrillation
Valvular Heart Disease
Deep Vein Thrombosis
Pulmonary Embolism
Peripheral Arterial Disease
Keywords: anticoagulation
warfarin
monitoring
bleeding
thromboembolism
Lead sponsor: McMaster University
Sponsor class: OTHER
First posted: 2012-07-31
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: More than 2 million patients in North America are treated with warfarin - a "blood thinner" - to prevent blood clots in arteries or veins. The treatment has to be monitored with a blood test and the dose changed accordingly every 1-4 weeks. One third of the patients have very stable results and hardly ever have to change the dose. The investigators wish to show that the level of control of the treatment with warfarin in these very stable patients is not worse with 12-weekly testing. A pilot study the investigators performed indicated that 12-weekly testing would be safe but this has to be confirmed in a large study. One third of patients taking warfarin have not had any changes in the dose for the past 6 months or longer. These patients will be asked about participation in the study. They will be randomized to testing and dosing every 4 or 12 weeks. Each patient is in the study until it ends, which will be minimum 1 year and can be up to about 4 years. The study is designed to show that 12-weekly testing does not significantly increase the risk for major bleeding or blood clots. The results would be important for a large number of patients. An increase of the interval between blood tests from 4 to 12 weeks would reduce the burden for these patients on life-long treatment considerably.

Detailed description: The study is a randomized, controlled, open-label, multi-center non-inferiority trial to demonstrate that the interval between internation normalized ration (INR) tests can be extended from the recommended 4 weeks to 12 weeks for patients with stable INRs. PROBE design. Patients receiving warfarin therapy that have exhibited INR stability, defined as no change in maintenance dose for at least 6 months, are potentially eligible for enrolment in the study. The primary outcome is a composite of major bleeding (ISTH criteria) plus objectively verified arterial or venous thromboembolism (excluding superficial thrombophlebitis) plus death related to thromboembolism. Justification: the study is not reflecting a "trade-off" scenario where one regimen is expected to be more effective at the cost of increased harm compared to the other regimen. Conversely, the potential disadvantage of the experimental regimen in this trial is increased variability in INR, which may result in an increased rate of low as well as high INRs and therefore potentially an increase of both types of clinical events.

Eligibility criteria: Inclusion Criteria:

* long-term warfarin for prophylaxis of arterial embolism due to atrial fibrillation or mechanical heart valve replacement OR secondary prophylaxis after VTE
* therapeutic INR range of 2.0-3.0 or 2.5-3.5
* anticoagulation therapy has been managed by the study site for at least 6 months prior to enrollment
* warfarin maintenance dose has remained unchanged for the previous 6 months or longer

Exclusion Criteria:

* Age \< 18 years
* Life expectancy of less than 1 year
* Congestive heart failure or other diagnosis where the condition or its treatment is expected to affect the stability of INR (e.g. cancer requiring chemotherapy)
* Attending physician believes that patient is not suitable for the study (for instance, psychiatric disorder; history of non-compliance; newly diagnosed disease which by itself, via the treatment required or the effects thereof may cause instability of INRs)
* Patients who perform self-testing
* Geographic inaccessibility
* Failure to obtain written consent

Primary outcomes:
measure: Composite of major bleeding and objectively verified arterial or venous thromboembolism
timeFrame: Average 3 years
Secondary outcomes:
measure: All-cause mortality
timeFrame: Average 3 years
measure: Any bleeding
timeFrame: Average 3 years
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: Hamilton Health Sciences - General Hospital
state: Ontario
Study officials:
affiliation: McMaster University
name: Sam Schulman, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Schulman S, Parpia S, Stewart C, Rudd-Scott L, Julian JA, Levine M. Warfarin dose assessment every 4 weeks versus every 12 weeks in patients with stable international normalized ratios: a randomized trial. Ann Intern Med. 2011 Nov 15;155(10):653-9, W201-3. doi: 10.7326/0003-4819-155-10-201111150-00003.
citation: Pengo V, Barbero F, Biasiolo A, Pegoraro C, Cucchini U, Iliceto S. A comparison between six- and four-week intervals in surveillance of oral anticoagulant treatment. Am J Clin Pathol. 2003 Dec;120(6):944-7. doi: 10.1309/U716-4E0X-H5UE-RKRV.