Atrial FibrillationPhase 2EXPLORE-XaNCT00742859
Phase 2 Study of the Safety, Tolerability and Pilot Efficacy of Oral Factor Xa Inhibitor Betrixaban Compared to Warfarin
A Phase 2 study testing betrixaban and Warfarin in people with Atrial Fibrillation, run by Portola Pharmaceuticals at 21 sites in 2 countries.
Trial summary
Prevention of stroke in patients with atrial fibrillation (AF). Hypothesis: In patients with non-valvular AF, orally administered betrixaban will provide similar or better efficacy and safety than warfarin and it will offer the advantage of not requiring dose adjustments due to international normalized ratios (INRs)… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atrial Fibrillation
- What is being tested?
- betrixaban and Warfarin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 508 participants
- Where
- 21 sitesin 2 countries
- Study dates
- Oct 2008to Nov 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
- Male or female, age ≥18 years.
- If the patient is a woman, she must be without reproductive potential (i.e., postmenopausal for ≥2 years or after hysterectomy).
- AF at the time of enrollment (randomization) or documented within the last year by Holter, ECG, rhythm strip, pacemaker or other intracardiac recording, resulting in an indication for anticoagulation with warfarin, acenocumerol, phenprocoumon, or other Vitamin K antagonist in the opinion of the treating physician.
- One or more of the following risk factor(s) for stroke:
- Age 75 years or older.
- Prior stroke, TIA or systemic (i.e., central nervous system) embolus at least 30 days remote from the time of screening.
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- Symptomatic congestive heart failure within 3 months echocardiography, radionuclide study or contrast angiography.
- Hypertension requiring pharmacological treatment.
- Diabetes.
- Age of 55 years or older and previous coronary artery disease or known peripheral artery disease.
Who cannot join
- Body weight less than 40 kg (88 lbs).
- Need for either hemodialysis or peritoneal dialysis (or likely to require it within one year).
- AF due to reversible causes (e.g., thyrotoxicosis, pericarditis, cardiac surgery, pulmonary embolism).
- Mechanical prosthetic valve (bioprosthetic valve is allowed) or valvular disease likely to be operated on within one year.
- History (including family history) or symptoms of a congenital or acquired bleeding disorder or vascular malformation; or a history of intracranial, retroperitoneal, or intraocular bleeding within the last 6 months; or is felt to be at high risk for bleeding for other reasons including from significant liver disease. This also includes gastrointestinal bleeding within 90 days before randomization or endoscopically verified ulcer disease within 30 days of screening.
- Conditions other than AF that require chronic anticoagulation (e.g. prosthetic mechanical heart valve).
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- Persistent, uncontrolled hypertension (SBP >160 mm Hg on repeated measurements).
- Active infective endocarditis.
- Scheduled major surgery.
- Planned pulmonary vein ablation or surgical procedure for cure of AF or flutter.
- Recent ischemic stroke, systemic embolic event or acute coronary syndrome within 30 days.
- Severe co-morbid condition with life expectancy of ≤1 year.
- Previous known history of genetic coagulopathy (e.g., Factor V Leiden, Protein C Deficiency, Protein S Deficiency, Antiphospholipid Syndrome, etc.).
- Evidence at Screening of:
- Platelet count <100,000/mm3.
- Serum alanine aminotransferase (ALT) or aspirate aminotransferase (AST) >2 times upper limit of normal (ULN).
- A history (including family history) of "Long QT Syndrome".
- Aspirin >162 mg daily.
- Use of verapamil (pending the availability of a drug interaction study with betrixaban).
- Active alcohol or drug abuse, or psychosocial reasons that make study participation impractical.
- Use of an investigational drug or device within the past 30 days.
- Inability to comply with INR monitoring or other protocol-related activities.
- Unable to give written informed consent.
Trial locations and contacts
21 sites in 2 countries.
21 sites in 2 countries
United States19 sites
Portola Investigational Site
Anaheim, California, 92801
Portola Investigational Site
Auburn, Maine, 04210
Portola Investigational Site
Aurora, Illinois, 60504
Portola Investigational Site
Colorado Springs, Colorado, 80909
Portola Investigational Site
Columbia, Maryland, 21044
Portola Investigational Site
Hillsboro, Oregon, 97123
Portola Investigational Site
Melbourne, Florida, 32901
Portola Investigational Site
Miami, Florida, 33173
Portola Investigational Site
Norfolk, Virginia, 23507
Portola Investigational Site
Ormond Beach, Florida, 32174
Portola Investigational Site
Pensacola, Florida, 32501
Portola Investigational Site
Port Charlotte, Florida, 33952
Portola Investigational Site
Poughkeepsie, New York, 12601
Portola Investigational Site
Rapid City, South Dakota, 57701
Portola Investigational Site
Salisbury, Maryland, 21804
Portola Investigational Site
St Louis, Missouri, 63110
Portola Investigational Site
Towson, Maryland, 21204
Portola Investigational Site
Tupelo, Mississippi, 38801
Portola Investigational Site
Wynnewood, Pennsylvania, 19096
Canada2 sites
Portola Investigational Site
Longueuil, Quebec
Portola Investigational Site
Montreal, Quebec
About this study
Official title: A Phase 2, Randomized, Parallel Group, Dose-Finding, Multicenter, Multinational Study of the Safety, Tolerability and Pilot Efficacy of Three Blinded Doses of the Oral Factor Xa Inhibitor Betrixaban Compared With Open-Label Dose-Adjusted Warfarin in Patients With Non-Valvular Atrial Fibrillation (EXPLORE Xa)
Prevention of stroke in patients with atrial fibrillation (AF). Hypothesis: In patients with non-valvular AF, orally administered betrixaban will provide similar or better efficacy and safety than warfarin and it will offer the advantage of not requiring dose adjustments due to international normalized ratios (INRs) outside the target range of 2.0 to 3.0 and a more consistent level of anticoagulation over time.
Read the detailed description
To assess the safety and tolerability of betrixaban at doses of 40 mg, 60 mg and 80 mg given orally once a day for at least 3 months compared to dose-adjusted warfarin in patients with non-valvular atrial fibrillation (AF).
This is a Phase 2, exploratory, randomized, parallel group, multicenter, active comparator, dose finding study of patients with documented non-valvular AF. Patients will be randomized (1:1:1:1) to 1 of 4 treatment groups (approximately 125 patients per group) using an interactive voice response system (IVRS). A dynamic randomization will be used to balance patients by country, concurrent aspirin use (yes or no) and antecedent warfarin (yes or no). The study will be open label for randomization to warfarin versus betrixaban, but the three daily doses of betrixaban, 40 mg, 60 mg or 80 mg, will be double-blind (identical capsules for all three dose levels). The warfarin-treated patients will be managed according to each center's usual clinical routine with INR monitoring and dose-adjustments in order to maintain a target INR of 2.0 to 3.0 at maximum intervals of four weeks. No loading doses or dose titrations will be used for betrixaban. The betrixaban dose should be ingested in the evening (e.g. at bedtime), preferably at least 2 hours after the evening meal. Note: acenocumerol may be substituted for warfarin as indicated by local practice.
- Conditions
- Atrial Fibrillation
- Being tested
- betrixaban, Warfarin
- Keywords
- Atrial Fibrillation, Betrixaban, Factor Xa inhibitor, Warfarin
- Medical subject headings
- Atrial Fibrillation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
betrixabanDrug
orally, once daily for at least 3 months
WarfarinDrug
Also called Coumadin, Acenocoumarol
Warfarin will be prescribed by the investigator according to the standard of care.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Betrixaban | Experimental | Betrixaban, 40 mg, orally, once daily for at least 3 months. Receives: Drug: betrixaban |
| Arm 2: Betrixaban | Experimental | Betrixaban, 60 mg, orally, once daily for at least 3 months Receives: Drug: betrixaban |
| Arm 3: Betrixaban | Experimental | Betrixaban, 80 mg, orally, once daily for at least 3 months Receives: Drug: betrixaban |
| Arm 4: Warfarin | Active comparator | Warfarin will be prescribed by investigators according to the standard of care. Receives: Drug: Warfarin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Exposure-adjusted Incidence Rate of Major or Clinically Relevant Non-major Bleeding Episode
The primary endpoint is the time to the first occurrence of major or clinically relevant non-major bleeding. This was presented as the exposure adjusted incidence rate which was calculated as number of subjects experiencing the event divided by total person years across all subjects, where if a patient experiencing the event, year was from first dose date to the first occurrence of the event, and to last study date if not. The confidence interval was calculated via the exact Poisson distribution.
Measured: A maximum of 1 year
Secondary outcomes (1)
Exposure-adjusted Incidence Rate of Any Bleeding (Major, Clinically Relevant Non-major, or Minimal)
The time to the first occurrence of any bleeding event. This was presented as the exposure adjusted incidence rate which was calculated as number of subjects experiencing the event divided by total person years across all subjects, where if a patient experiencing the event, year was from first dose date to the first occurrence of the event, and to last study date if not. The confidence interval was calculated via the exact Poisson distribution.
Measured: A maximum of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2008 (estimated)
- Study startOct 2008
- Primary completionAug 2009
- Study completionNov 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.
- 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 508 participants (actual)
Sponsor and investigators
- Lead sponsor
- Portola Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Stuart Connolly, MD, FRCP, Study chair, Population Health Research Institute, McMaster UniversityRafael Diaz, MD, Study director, Instituto Cardiovascular de Rosario, ArgentinaPaul Dorian, MD, Study director, University of Toronto, CanadaMichael Ezekowitz, MD, PhD,, Study director, Lankenau Institute for Medical Research and The Heart Center, United StatesStefan H. Hohnloser, MD, Study director, Johann Wolgang Goethe University, Frankfurt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00742859
- Sponsor's protocol ID
- 08-015
- Acronym
- EXPLORE-Xa
- Status last verified
- Aug 2023
- First submitted
- 26 Aug 2008
- Last updated
- 7 Aug 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Randomized, Parallel Group, Dose-Finding, Multicenter, Multinational Study of the Safety, Tolerability and Pilot Efficacy of Three Blinded Doses of the Oral Factor Xa Inhibitor Betrixaban Compared With Open-Label Dose-Adjusted Warfarin in Patients With Non-Valvular Atrial Fibrillation (EXPLORE Xa)
- ClinicalTrials.gov ID
- NCT00742859
- Acronym / sponsor ID
- EXPLORE-Xa / 08-015
- Conditions
- Atrial Fibrillation
- Keywords
- Atrial Fibrillation, Betrixaban, Factor Xa inhibitor, Warfarin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 508 participants (actual)
- Lead sponsor
- Portola PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Oct 2008
- Primary completion
- Aug 2009 (actual)
- Study completion
- Nov 2009 (actual)
- First posted
- 28 Aug 2008 (estimated)
- Results
- Posted 26 Sep 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Prevention of stroke in patients with atrial fibrillation (AF). Hypothesis: In patients with non-valvular AF, orally administered betrixaban will provide similar or better efficacy and safety than warfarin and it will offer the advantage of not requiring dose adjustments due to international normalized ratios (INRs) outside the target range of 2.0 to 3.0 and a more consistent level of anticoagulation over time.
Detailed description
To assess the safety and tolerability of betrixaban at doses of 40 mg, 60 mg and 80 mg given orally once a day for at least 3 months compared to dose-adjusted warfarin in patients with non-valvular atrial fibrillation (AF).
This is a Phase 2, exploratory, randomized, parallel group, multicenter, active comparator, dose finding study of patients with documented non-valvular AF. Patients will be randomized (1:1:1:1) to 1 of 4 treatment groups (approximately 125 patients per group) using an interactive voice response system (IVRS). A dynamic randomization will be used to balance patients by country, concurrent aspirin use (yes or no) and antecedent warfarin (yes or no). The study will be open label for randomization to warfarin versus betrixaban, but the three daily doses of betrixaban, 40 mg, 60 mg or 80 mg, will be double-blind (identical capsules for all three dose levels). The warfarin-treated patients will be managed according to each center's usual clinical routine with INR monitoring and dose-adjustments in order to maintain a target INR of 2.0 to 3.0 at maximum intervals of four weeks. No loading doses or dose titrations will be used for betrixaban. The betrixaban dose should be ingested in the evening (e.g. at bedtime), preferably at least 2 hours after the evening meal. Note: acenocumerol may be substituted for warfarin as indicated by local practice.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Arm 1: Betrixaban | Experimental | Drug: betrixabanBetrixaban, 40 mg, orally, once daily for at least 3 months. |
| Arm 2: Betrixaban | Experimental | Drug: betrixabanBetrixaban, 60 mg, orally, once daily for at least 3 months |
| Arm 3: Betrixaban | Experimental | Drug: betrixabanBetrixaban, 80 mg, orally, once daily for at least 3 months |
| Arm 4: Warfarin | Active comparator | Drug: WarfarinWarfarin will be prescribed by investigators according to the standard of care. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Male or female, age ≥18 years.
- If the patient is a woman, she must be without reproductive potential (i.e., postmenopausal for ≥2 years or after hysterectomy).
- AF at the time of enrollment (randomization) or documented within the last year by Holter, ECG, rhythm strip, pacemaker or other intracardiac recording, resulting in an indication for anticoagulation with warfarin, acenocumerol, phenprocoumon, or other Vitamin K antagonist in the opinion of the treating physician.
- One or more of the following risk factor(s) for stroke:
Key exclusion criteria (23 listed)
- Body weight less than 40 kg (88 lbs).
- Need for either hemodialysis or peritoneal dialysis (or likely to require it within one year).
- AF due to reversible causes (e.g., thyrotoxicosis, pericarditis, cardiac surgery, pulmonary embolism).
- Mechanical prosthetic valve (bioprosthetic valve is allowed) or valvular disease likely to be operated on within one year.
- History (including family history) or symptoms of a congenital or acquired bleeding disorder or vascular malformation; or a history of intracranial, retroperitoneal, or intraocular bleeding within the last 6 months; or is felt to be at high risk for bleeding for other reasons including from significant liver disease. This also includes gastrointestinal bleeding within 90 days before randomization or endoscopically verified ulcer disease within 30 days of screening.
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 |
|---|---|---|
| betrixabanorally, once daily for at least 3 months | Drug | Arm 1: Betrixaban, Arm 2: Betrixaban, Arm 3: Betrixaban |
| WarfarinAlso: Coumadin, AcenocoumarolWarfarin will be prescribed by the investigator according to the standard of care. | Drug | Arm 4: Warfarin |
Primary outcome
Exposure-adjusted Incidence Rate of Major or Clinically Relevant Non-major Bleeding Episode
Time frame: A maximum of 1 year
The primary endpoint is the time to the first occurrence of major or clinically relevant non-major bleeding. This was presented as the exposure adjusted incidence rate which was calculated as number of subjects experiencing the event divided by total person years across all subjects, where if a patient experiencing the event, year was from first dose date to the first occurrence of the event, and to last study date if not. The confidence interval was calculated via the exact Poisson distribution.
1 secondary outcome
Exposure-adjusted Incidence Rate of Any Bleeding (Major, Clinically Relevant Non-major, or Minimal)
Time frame: A maximum of 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Atrial Fibrillation (AF)
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.
Stuart Connolly, MD, FRCP study chair
Population Health Research Institute, McMaster University
Rafael Diaz, MD study director
Instituto Cardiovascular de Rosario, Argentina
Paul Dorian, MD study director
University of Toronto, Canada
21 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing betrixaban and Warfarin in people with Atrial Fibrillation, run by Portola Pharmaceuticals at 21 sites in 2 countries.
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 10 inclusion and 23 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 7 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in United States, 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 26 Sep 2017). 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?
Exposure-adjusted Incidence Rate of Major or Clinically Relevant Non-major Bleeding Episode (time frame: A maximum of 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Aug 2023.