Prolongation of the Interval Between Prothrombin Time Tests in Stable Patients II (PRINT-II)

This study has been withdrawn prior to enrollment.
(No funding obtained)
Sponsor:
Information provided by (Responsible Party):
Sam Schulman, McMaster University
ClinicalTrials.gov Identifier:
NCT01654042
First received: July 21, 2012
Last updated: March 18, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Atrial Fibrillation
Valvular Heart Disease
Deep Vein Thrombosis
Pulmonary Embolism
Peripheral Arterial Disease
Other: Prolonged interval between PT testing
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by McMaster University:

Primary Outcome Measures:
  • Composite of major bleeding and objectively verified arterial or venous thromboembolism [ Time Frame: Average 3 years ] [ Designated as safety issue: Yes ]
    The justification for a composite outcome including both bleeding and thromboembolism is that 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 prothrombin time, which may result in an increased rate of short as well as long prothrombin times and therefore potentially an increase of both types of clinical events.


Secondary Outcome Measures:
  • All-cause mortality [ Time Frame: Average 3 years ] [ Designated as safety issue: Yes ]
  • Any bleeding [ Time Frame: Average 3 years ] [ Designated as safety issue: Yes ]
    This is the composite of major and minor bleeding


Enrollment: 0
Study Start Date: April 2014
Estimated Study Completion Date: October 2018
Estimated Primary Completion Date: April 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Standard interval between PT testing
Prothrombin time (PT) is tested every 4 weeks, according to American College of Chest Physicians (ACCP) Guidelines up to 2008 for stable patients on warfarin.
Experimental: Prolonged interval between PT testing
Prothrombin time (PT) is tested every 12 weeks, according to suggestion in American College of Chest Physicians (ACCP) Guidelines of 2012 for stable patients on warfarin.
Other: Prolonged interval between PT testing
Patients in the intervention group will be scheduled for prothrombin time testing and dosing of warfarin every 12 weeks instead of every 4 weeks. This has been suggested in the latest edition of the ACCP guidelines as a possibility for very stable patients. In order to change this from a suggestion to a formal recommendation a study powered for clinically important outcomes is needed.
Other Name: INR (International Normalized Ratio) tests

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01654042

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

Publications:
Responsible Party: Sam Schulman, SSchulman, McMaster University
ClinicalTrials.gov Identifier: NCT01654042     History of Changes
Other Study ID Numbers: PRINT-II-2012
Study First Received: July 21, 2012
Last Updated: March 18, 2014
Health Authority: Canada: Health Canada

Keywords provided by McMaster University:
anticoagulation
warfarin
monitoring
bleeding
thromboembolism

Additional relevant MeSH terms:
Atrial Fibrillation
Embolism
Heart Diseases
Heart Valve Diseases
Pulmonary Embolism
Thrombosis
Venous Thrombosis
Peripheral Arterial Disease
Peripheral Vascular Diseases
Arrhythmias, Cardiac
Cardiovascular Diseases
Pathologic Processes
Embolism and Thrombosis
Vascular Diseases
Lung Diseases
Respiratory Tract Diseases
Atherosclerosis
Arteriosclerosis
Arterial Occlusive Diseases
Thrombin
Warfarin
Hemostatics
Coagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Anticoagulants

ClinicalTrials.gov processed this record on July 20, 2014