Nonvalvular Atrial FibrillationPhase 2NCT00684307
Prevention of Stroke and Systemic Embolic Events in Patients With Atrial Fibrillation
A Phase 2 study testing AZD0837 and Vitamin-K antagonist at INR 2-3 in people with Nonvalvular Atrial Fibrillation, run by AstraZeneca.
Trial summary
The main purpose of this study is to provide dose-guiding information by assessing the safety and tolerability of 4 different dosing regimens of an extended-release (ER) formulation of AZD0837 compared with well-controlled, dose-adjusted Vitamin-K antagonists (VKA) (aiming for an international normalized ratio (INR)… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Nonvalvular Atrial Fibrillation
- What is being tested?
- AZD0837 and Vitamin-K antagonist at INR 2-3
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,084 participants
- Where
- No sites listed yet
- Study dates
- Feb 2007to Jun 2008
- 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
- Nonvalvular AF (NVAF) verified by at least two ECGs in the last year separated by at least one week.
- Previous cerebral ischemic attack (stroke or TIA, >30 days prior to randomization)
- Previous systemic embolism.
- Symptomatic congestive heart failure (CHF)
- Impaired left ventricular systolic function
- Diabetes mellitus
- Hypertension requiring anti-hypertensive treatment.
Who cannot join
- AF secondary to reversible disorders, eg hyperthyroidism, drugs and pulmonary embolism
- Known contraindication to VKA treatment
- Presence of a valvular heart disease, mechanical heart valves, active endocarditis, left ventricular aneurysm or thrombus, atrial myxoma or any condition other than AF requiring chronic anticoagulation treatment
- Conditions associated with increased risk of major bleeding for example: history of intracranial bleeding, history of bleeding gastrointestinal disorder or major surgical procedure or trauma two weeks prior to randomization
About this study
Official title: A Controlled, Randomized, Parallel, Multicentre Study to Assess Safety and Tolerability of the Oral Direct Thrombin Inhibitor AZD0837, Given as an Extended-release Formulation, in the Prevention of Stroke and Systemic Embolic Events in Patients With Atrial Fibrillation
The main purpose of this study is to provide dose-guiding information by assessing the safety and tolerability of 4 different dosing regimens of an extended-release (ER) formulation of AZD0837 compared with well-controlled, dose-adjusted Vitamin-K antagonists (VKA) (aiming for an international normalized ratio (INR) 2.0 to 3.0) in patients with non-valvular atrial fibrillation (AF) with one or more additional risk factors for stroke.
- Conditions
- Nonvalvular Atrial Fibrillation
- Being tested
- AZD0837, Vitamin-K antagonist at INR 2-3
- Keywords
- Anticoagulant Treatment, Risk Factors For Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD0837Drug
ER tablet, PO, once daily for a period of 3-9 months.
Vitamin-K antagonist at INR 2-3Drug
Also called Warfarin
Tablet, PO for a period of 3-9 months.
AZD0837Drug
ER tablet, PO, twice daily for a period of 3-9 months
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | AZD0837 450 mg Receives: Drug: AZD0837 |
| 2 | Experimental | AZD0837 200 mg Receives: Drug: AZD0837 |
| 3 | Experimental | AZD0837 300 mg Receives: Drug: AZD0837 |
| 4 | Experimental | AZD0837 150 mg Receives: Drug: AZD0837 |
| 5 | Active comparator | Vitamin-K antagonist at INR 2-3 Receives: Drug: Vitamin-K antagonist at INR 2-3 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bleeding Events
Number of patients with a bleeding event while on study drug. Patients with multiple events are counted once
Measured: 36 weeks according to protocol. For patients who discontinued treatment the time frame was <36 weeks. Mean number of weeks was 21 weeks (baseline to end of treatment visit)
Creatinine
Change in Creatinine values from baseline to week 12 visit for patients while on study drug (week 12 visit-baseline)
Measured: 12 weeks according to protocol.(baseline to week 12 visit)
Alanine Aminotransferase (ALAT)
Number of patients while on study drug with ALAT>=3 times upper limit of normal.l
Measured: 36 weeks according to protocol. For patients who discontinued treatment the time frame was <36 weeks. Mean number of weeks was 21 weeks (baseline to end of treatment visit)
Bilirubin
Number of patients while on study drug with Bilirubin>=2 times upper limit of normal
Measured: 36 weeks according to protocol. For patients who discontinued treatment the time frame was <36 weeks. Mean number of weeks was 21 weeks (baseline to end of treatment visit)
Secondary outcomes (8)
D-Dimer
Change in D-Dimer values from enrolment to week 12 visit for VKA naïve patients while on study drug (week 12 visit-enrolment)
Measured: 14 weeks according to protocol.(enrolment to week 12 visit)
Activated Partial Thromboplastin Time (APTT)
Change in Activated partial thromboplastin time (APTT) from baseline to week 12 visit for VKA naïve patients while on study drug (week 12 visit-baseline)
Measured: 12 weeks according to protocol.(baseline to week 12 visit)
Ecarin Clotting Time (ECT)
Change in Ecarin clotting time (ECT) from baseline to week 12 visit for patients while on study drug (week 12 visit-baseline)
Measured: 12 weeks according to protocol.(baseline to week 12 visit)
Plasma Concentration of AZD0837 (Prodrug)
Assessment made on the week 12 visit
Measured: 12 weeks after baseline according to protocol
Plasma Concentration of AR-H067637XX (Active Metabolite)
Assessment made on the week 12 visit
Measured: 12 weeks after baseline according to protocol
Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype TT
Oral clearance of AR-H067637XX in subgroup of patients with genotype TT for gene polymorphism ABCB1 C3435T
Measured: 36 weeks according to protocol
Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype TC
Oral clearance of AR-H067637XX in subgroup of patients with genotype TC for gene polymorphism ABCB1 C3435T
Measured: 36 weeks according to protocol
Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype CC
Oral clearance of AR-H067637XX in subgroup of patients with genotype CC for gene polymorphism ABCB1 C3435T
Measured: 36 weeks according to protocol
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2008 (estimated)
- Study startFeb 2007
- Primary completionJun 2008
- Study completionJun 2008
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 Nonvalvular Atrial FibrillationStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 1,084 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gregory Y Lip, Prof, Principal investigator, University Department of Medicine, City Hospital, Birmingham, B18 7QH, England, UK
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00684307
- Sponsor's protocol ID
- D1250C00008
- Status last verified
- Mar 2012
- First submitted
- 22 May 2008
- Last updated
- 23 Mar 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Lip GY, Rasmussen LH, Olsson SB, Jensen EC, Persson AL, Eriksson U, Wahlander KF; Steering Committee. Oral direct thrombin inhibitor AZD0837 for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation: a randomized dose-guiding, safety, and tolerability study of four doses of AZD0837 vs. vitamin K antagonists. Eur Heart J. 2009 Dec;30(23):2897-907. doi: 10.1093/eurheartj/ehp318. Epub 2009 Aug 18.
PubMed 19690349
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Controlled, Randomized, Parallel, Multicentre Study to Assess Safety and Tolerability of the Oral Direct Thrombin Inhibitor AZD0837, Given as an Extended-release Formulation, in the Prevention of Stroke and Systemic Embolic Events in Patients With Atrial Fibrillation
- ClinicalTrials.gov ID
- NCT00684307
- Acronym / sponsor ID
- D1250C00008
- Conditions
- Nonvalvular Atrial Fibrillation
- Keywords
- Anticoagulant Treatment, Risk Factors For Stroke
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,084 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- Feb 2007
- Primary completion
- Jun 2008 (actual)
- Study completion
- Jun 2008 (actual)
- First posted
- 26 May 2008 (estimated)
- Results
- Posted 22 Sep 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main purpose of this study is to provide dose-guiding information by assessing the safety and tolerability of 4 different dosing regimens of an extended-release (ER) formulation of AZD0837 compared with well-controlled, dose-adjusted Vitamin-K antagonists (VKA) (aiming for an international normalized ratio (INR) 2.0 to 3.0) in patients with non-valvular atrial fibrillation (AF) with one or more additional risk factors for stroke.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: AZD0837AZD0837 450 mg |
| 2 | Experimental | Drug: AZD0837AZD0837 200 mg |
| 3 | Experimental | Drug: AZD0837AZD0837 300 mg |
| 4 | Experimental | Drug: AZD0837AZD0837 150 mg |
| 5 | Active comparator | Drug: Vitamin-K antagonist at INR 2-3Vitamin-K antagonist at INR 2-3 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Nonvalvular AF (NVAF) verified by at least two ECGs in the last year separated by at least one week.
- Previous cerebral ischemic attack (stroke or TIA, >30 days prior to randomization)
- Previous systemic embolism.
- Symptomatic congestive heart failure (CHF)
- Impaired left ventricular systolic function
Key exclusion criteria (4 listed)
- AF secondary to reversible disorders, eg hyperthyroidism, drugs and pulmonary embolism
- Known contraindication to VKA treatment
- Presence of a valvular heart disease, mechanical heart valves, active endocarditis, left ventricular aneurysm or thrombus, atrial myxoma or any condition other than AF requiring chronic anticoagulation treatment
- Conditions associated with increased risk of major bleeding for example: history of intracranial bleeding, history of bleeding gastrointestinal disorder or major surgical procedure or trauma two weeks prior to randomization
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 |
|---|---|---|
| AZD0837ER tablet, PO, once daily for a period of 3-9 months. | Drug | 1, 3, 4 |
| Vitamin-K antagonist at INR 2-3Also: WarfarinTablet, PO for a period of 3-9 months. | Drug | 5 |
| AZD0837ER tablet, PO, twice daily for a period of 3-9 months | Drug | 2 |
Primary outcome
Bleeding Events
Time frame: 36 weeks according to protocol. For patients who discontinued treatment the time frame was <36 weeks. Mean number of weeks was 21 weeks (baseline to end of treatment visit)
Number of patients with a bleeding event while on study drug. Patients with multiple events are counted once
Creatinine
Time frame: 12 weeks according to protocol.(baseline to week 12 visit)
Change in Creatinine values from baseline to week 12 visit for patients while on study drug (week 12 visit-baseline)
Alanine Aminotransferase (ALAT)
Time frame: 36 weeks according to protocol. For patients who discontinued treatment the time frame was <36 weeks. Mean number of weeks was 21 weeks (baseline to end of treatment visit)
Number of patients while on study drug with ALAT>=3 times upper limit of normal.l
Bilirubin
Time frame: 36 weeks according to protocol. For patients who discontinued treatment the time frame was <36 weeks. Mean number of weeks was 21 weeks (baseline to end of treatment visit)
Number of patients while on study drug with Bilirubin>=2 times upper limit of normal
8 secondary outcomes
D-Dimer
Time frame: 14 weeks according to protocol.(enrolment to week 12 visit)
Activated Partial Thromboplastin Time (APTT)
Time frame: 12 weeks according to protocol.(baseline to week 12 visit)
Ecarin Clotting Time (ECT)
Time frame: 12 weeks according to protocol.(baseline to week 12 visit)
Plasma Concentration of AZD0837 (Prodrug)
Time frame: 12 weeks after baseline according to protocol
Plasma Concentration of AR-H067637XX (Active Metabolite)
Time frame: 12 weeks after baseline according to protocol
Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype TT
Time frame: 36 weeks according to protocol
Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype TC
Time frame: 36 weeks according to protocol
Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype CC
Time frame: 36 weeks according to protocol
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 19690349Lip GY, Rasmussen LH, Olsson SB, Jensen EC, Persson AL, Eriksson U, Wahlander KF; Steering Committee. Oral direct thrombin inhibitor AZD0837 for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation: a randomized dose-guiding, safety, and tolerability study of four doses of AZD0837 vs. vitamin K antagonists. Eur Heart J. 2009 Dec;30(23):2897-907. doi: 10.1093/eurheartj/ehp318. Epub 2009 Aug 18.
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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.
Gregory Y Lip, Prof principal investigator
University Department of Medicine, City Hospital, Birmingham, B18 7QH, England, UK
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AZD0837 and Vitamin-K antagonist at INR 2-3 in people with Nonvalvular Atrial Fibrillation, run by AstraZeneca.
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 7 inclusion and 4 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 23 Mar 2012. Status can change between updates, so confirm with the study contact before making plans.
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 22 Sep 2011). 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?
Bleeding Events (time frame: 36 weeks according to protocol. For patients who discontinued treatment the time frame was <36 weeks. Mean number of weeks was 21 weeks (baseline to end of treatment visit)). The study lists 4 primary outcomes in all. 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 NCT00684307, 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 23 Mar 2012; AzTrials last refreshed its copy on 26 Oct 2026.