Atrial FibrillationPhase 3PRINT-IINCT01654042
Prolongation of the Interval Between Prothrombin Time Tests in Stable Patients II
A Phase 3 study testing Prolonged interval between PT testing in people with Atrial Fibrillation and Valvular Heart Disease, run by McMaster University at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atrial Fibrillation, Valvular Heart Disease, Deep Vein Thrombosis
- What is being tested?
- Prolonged interval between PT testing
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteCanada
- Study dates
- Apr 2014to Oct 2018
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Canada1 site
Hamilton Health Sciences - General Hospital
Hamilton, Ontario, L8L 2X2
About this study
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
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.
Read the 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.
- Conditions
- Atrial Fibrillation, Valvular Heart Disease, Deep Vein Thrombosis, Pulmonary Embolism, Peripheral Arterial Disease
- Being tested
- Prolonged interval between PT testing
- Keywords
- anticoagulation, warfarin, monitoring, bleeding, thromboembolism
- Medical subject headings
- Atrial Fibrillation, Heart Valve Diseases, Venous Thrombosis, Pulmonary Embolism, Peripheral Arterial Disease, Hemorrhage, Thromboembolism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Prolonged interval between PT testingOther
Also called INR (International Normalized Ratio) tests
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.
| Study group | Role | What they receive |
|---|---|---|
| Standard interval between PT testing | No intervention | 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. |
| Prolonged interval between PT testing | Experimental | 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. Receives: Other: Prolonged interval between PT testing |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite of major bleeding and objectively verified arterial or venous thromboembolism
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.
Measured: Average 3 years
Secondary outcomes (2)
All-cause mortality
Measured: Average 3 years
Any bleeding
This is the composite of major and minor bleeding
Measured: Average 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2012 (estimated)
- Study startApr 2014
- Primary completionApr 2018 (estimated)
- Study completionOct 2018 (estimated)
Why it stopped: No funding obtained
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Atrial FibrillationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- McMaster University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sam Schulman, McMaster University
- Investigators
- Sam Schulman, MD, PhD, Principal investigator, McMaster University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01654042
- Sponsor's protocol ID
- PRINT-II-2012
- Acronym
- PRINT-II
- Status last verified
- Mar 2014
- First submitted
- 21 Jul 2012
- Last updated
- 20 Mar 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 22084331Pengo 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.
PubMed 14671984
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01654042
- Acronym / sponsor ID
- PRINT-II / PRINT-II-2012
- Conditions
- Atrial Fibrillation, Valvular Heart Disease, Deep Vein Thrombosis, Pulmonary Embolism, Peripheral Arterial Disease
- Keywords
- anticoagulation, warfarin, monitoring, bleeding, thromboembolism
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: No funding obtained
- Enrolment
- 0 participants (actual)
- Lead sponsor
- McMaster UniversityUniversity, hospital or other
- Study start
- Apr 2014
- Primary completion
- Apr 2018 (estimated)
- Study completion
- Oct 2018 (estimated)
- First posted
- 31 Jul 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard interval between PT testing | No intervention | –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. |
| Prolonged interval between PT testing | Experimental | Other: Prolonged interval between PT testingProthrombin 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Prolonged interval between PT testingAlso: INR (International Normalized Ratio) testsPatients 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 | Prolonged interval between PT testing |
Primary outcome
Composite of major bleeding and objectively verified arterial or venous thromboembolism
Time frame: Average 3 years
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.
2 secondary outcomes
All-cause mortality
Time frame: Average 3 years
Any bleeding
Time frame: Average 3 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2014.
- Background: PubMed 22084331Schulman 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.
- Background: PubMed 14671984Pengo 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sam Schulman, MD, PhD principal investigator
McMaster University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Prolonged interval between PT testing in people with Atrial Fibrillation and Valvular Heart Disease, run by McMaster University at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 20 Mar 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite of major bleeding and objectively verified arterial or venous thromboembolism (time frame: Average 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01654042, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2014.