Atrial FibrillationPhase 2FORESPEAK-0NCT00814177
Prothrombin Times Outside the Therapeutic Range in Otherwise Stable Patients
A Phase 2 study testing warfarin in people with Atrial Fibrillation and Venous Thromboembolism, run by Hamilton Health Sciences Corporation at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atrial Fibrillation, Venous Thromboembolism, Ischemic Stroke
- What is being tested?
- warfarin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 160 participants
- Where
- 1 siteCanada
- Study dates
- Jul 2006to Apr 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Canada1 site
Thrombosis Service, HHS-General Hospital
Hamilton, Ontario, L8L 2X2
About this study
Official title: Management of Prothrombin Times Outside the Therapeutic Range in Patients on Warfarin and With Otherwise Stable Levels
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".
Read more
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.
Read the detailed description
Setting:
Thrombosis Service at HHS - General Hospital. This center monitors the warfarin treatment for 1300 patients in the region. These patient regularly go to a laboratory where they live. Test results (INR-results) are faxed to the Thrombosis Service, which calls the patient the same day to inform them of the results, how to continue dosing the warfarin and when to go for the following blood test.
- Being tested
- warfarin
- Keywords
- warfarin, dosing, prothrombin time, Heart valve prosthesis
- Medical subject headings
- Atrial Fibrillation, Venous Thromboembolism, Ischemic Stroke, Myocardial Infarction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
warfarinDrug
Also called Coumadin
No change: Continue without any change in spite of prothrombin time outside the therapeutic range.
warfarinDrug
Also called Coumadin
Change: Increase one dose in case prothrombin time is below the therapeutic range; delete or reduce one dose in case prothrombin time is above the therapeutic range.
| Study group | Role | What they receive |
|---|---|---|
| No change | Experimental | Intervention Drug warfarin no change in the dose is performed Receives: Drug: warfarin |
| Change | Active comparator | Intervention Drug Warfarin One dose increased if subtherapeutic level; one dose deleted or reduced if supratherapeutic level Receives: Drug: warfarin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2008 (estimated)
- Study startJul 2006
- Primary completionJan 2009
- Study completionApr 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 160 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hamilton Health Sciences Corporation
- 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
- NCT00814177
- Sponsor's protocol ID
- HRC060425
- Acronym
- FORESPEAK-0
- Status last verified
- Jul 2012
- First submitted
- 23 Dec 2008
- Last updated
- 1 Aug 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 19640572
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Management of Prothrombin Times Outside the Therapeutic Range in Patients on Warfarin and With Otherwise Stable Levels
- ClinicalTrials.gov ID
- NCT00814177
- Acronym / sponsor ID
- FORESPEAK-0 / HRC060425
- Keywords
- warfarin, dosing, prothrombin time, Heart valve prosthesis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 160 participants (actual)
- Lead sponsor
- Hamilton Health Sciences CorporationUniversity, hospital or other
- Study start
- Jul 2006
- Primary completion
- Jan 2009 (actual)
- Study completion
- Apr 2009 (actual)
- First posted
- 24 Dec 2008 (estimated)
- Results
- Posted 25 Nov 2009
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Setting:
Thrombosis Service at HHS - General Hospital. This center monitors the warfarin treatment for 1300 patients in the region. These patient regularly go to a laboratory where they live. Test results (INR-results) are faxed to the Thrombosis Service, which calls the patient the same day to inform them of the results, how to continue dosing the warfarin and when to go for the following blood test.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| No change | Experimental | Drug: warfarinIntervention Drug warfarin no change in the dose is performed |
| Change | Active comparator | Drug: warfarinIntervention Drug Warfarin One dose increased if subtherapeutic level; one dose deleted or reduced if supratherapeutic level |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
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 |
|---|---|---|
| warfarinAlso: CoumadinNo change: Continue without any change in spite of prothrombin time outside the therapeutic range. | Drug | No change |
| warfarinAlso: CoumadinChange: Increase one dose in case prothrombin time is below the therapeutic range; delete or reduce one dose in case prothrombin time is above the therapeutic range. | Drug | Change |
Primary outcome
Number of Patients With Prothrombin Time Results Within the Therapeutic Range After 2 Weeks
Time frame: 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 19640572Schulman 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.
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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 2 study testing warfarin in people with Atrial Fibrillation and Venous Thromboembolism, run by Hamilton Health Sciences Corporation 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 5 inclusion and 5 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: finished, as of the sponsor's last update on 1 Aug 2012. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Nov 2009). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Patients With Prothrombin Time Results Within the Therapeutic Range After 2 Weeks (time frame: 2 weeks). 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 NCT00814177, which also lists 1 linked publication.
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 1 Aug 2012.