Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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This study has been withdrawn prior to enrollment.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

July 21, 2012
March 18, 2014
April 2014
April 2018   (final data collection date for primary outcome measure)
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.
Same as current
Complete list of historical versions of study NCT01654042 on ClinicalTrials.gov Archive Site
  • 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
Same as current
Not Provided
Not Provided
 
Prolongation of the Interval Between Prothrombin Time Tests in Stable Patients II
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

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Atrial Fibrillation
  • Valvular Heart Disease
  • Deep Vein Thrombosis
  • Pulmonary Embolism
  • Peripheral Arterial Disease
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
  • 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.
    Intervention: Other: Prolonged interval between PT testing

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Withdrawn
0
October 2018
April 2018   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Canada
 
NCT01654042
PRINT-II-2012
No
Sam Schulman, McMaster University
McMaster University
Not Provided
Principal Investigator: Sam Schulman, MD, PhD McMaster University
McMaster University
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP