FindTrial
Sign In

Long-term Safety in Atrial Fibrillation Patients

Long-term Treatment With the Oral Direct Thrombin Inhibitor AZD0837, Compared to Vitamin-K Antagonists, as Stroke Prevention in Patients With Non-valvular Atrial Fibrillation and One or More Risk Factors for Stroke and Systemic Embolic Events. A 5-year Follow-up Study

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00645853
Enrollment
523
Registered
2008-03-28
Start date
2007-10-31
Completion date
2009-05-31
Last updated
2012-03-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Persistent or Permanent Nonvalvular Atrial Fibrillation

Brief summary

The purpose of this study is to provide safety and tolerability data for AZD0837 during long-term treatment (5 years) in patients with non-valvular atrial fibrillation (AF) and one or more additional risk factors for stroke and systemic embolic events (moderate to high risk patients).

Interventions

DRUGAZD0837

Treatment with AZD0837 starting with 4 different doses, 150 mg od, 300 mg od, 200 mg bid or 450 mg od and then switching to one general common dose, 300 mg od

DRUGVKA INR 2-3

Vitamin K antagonists (VKA), titrated to an international normalised ratio (INR) of 2.0 to 3.0 with a target value of 2.5

Sponsors

AstraZeneca
Lead SponsorINDUSTRY

Study design

Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion criteria

* Patients with paroxysmal, persistent or permanent Non Valvular Atrial Fibrillation with one or more additional risk factors for stroke and systemic embolic event * completing treatment with study drug in D1250C00008.

Exclusion criteria

* Atrial Fibrillation secondary to reversible disorders, eg hyperthyroidism * Presence of a valvular heart disease, mechanical heart valves, active endocarditis, left ventricular aneurysm or thrombus, atrial myxoma or any condition other than Atrial Fibrillation requiring chronic anticoagulation treatment * Myocardial infarction, heart surgery or percutaneous coronary intervention (PCI) within the previous three months prior to inclusion; Stroke and/or systemic embolism within the previous 30 days prior to inclusion * Conditions associated with increased risk of major bleeding.

Design outcomes

Primary

MeasureTime frameDescription
Bleeding: Number of Patients With Any Bleeding Event, During Treatment Period154-711 days on treatmentParticipants

Secondary

MeasureTime frameDescription
Bilirubin: Number of Patients With Bilirubin>=2xULN, Post BaselineFrom baseline to Follow up—
Creatinine: Absolute Change From Baseline, at End of TreatmentBaseline and End of treatment—
D-dimer:Median and Quartile Range at End of TreatmentEnd of treatmentMedian (Lower Quartile-Upper Quartile ), ng/mL
Alanine Transaminase (ALAT): Number of Patients With ALAT>=3xULN, Post BaselineFrom baseline to Follow upULN=Upper limit of Normal
Electroconvulsive Therapy (ECT): Absolute Change From Baseline to End of TreatmentBaseline and End of Treatment—
AZD0837: Plasma Concentration of AZD0837 at End of TreatmentEnd of treatment—
AR-H067637XX, the Active Major Metabolite of AD0837: Plasma Concentration of AR-H067637XX, at End of Treatment154-711 days on treatment—
Activated Partial Thromboplastin Time (APTT): Absolute Change From Baseline to End of TreatmentBaseline and End of treatmentMedian Full range, Seconds

Participant flow

Recruitment details

The study population included male and female participants \>18 years of age with chronic non-valvular Atrial Fibrillation. The participants were recruited during the time period from 25 October 2007 to 20 May 2008 at medical clinics in Europe.

Pre-assignment details

All participants had previously participated in the Prevention of Stroke and Systemic Embolic Events in Patients With Atrial Fibrillation (NCT00684307) study

Participants by arm

ArmCount
AZD0837
Treatment with AZD0837 starting with 4 different doses, 150 mg od, 300 mg od, 200 mg bid or 450 mg od, then switching to one general common dose, 300 mg od.
288
VKA, INR 2-3
Vitamin K antagonists (VKA), titrated to an international normalised ratio (INR) of 2.0 to 3.0 with a target value of 2.5
235
Total523

Withdrawals & dropouts

PeriodReasonFG000FG001
Overall StudyAdverse Event187
Overall StudyAZ study closure in Hungary6040
Overall StudyDiscontinuation criteria22
Overall StudyProtocol Violation02
Overall Studyrecall of ICF, planned operation, death74
Overall StudyWithdrawal by Subject52

Baseline characteristics

CharacteristicAZD0837VKA, INR 2-3Total
Age Continuous69.9 Years68.0 Years68.95 Years
Sex: Female, Male
Female
90 Participants73 Participants163 Participants
Sex: Female, Male
Male
198 Participants162 Participants360 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
— / —— / —
other
Total, other adverse events
125 / 288106 / 235
serious
Total, serious adverse events
73 / 28861 / 235

Outcome results

Primary

Bleeding: Number of Patients With Any Bleeding Event, During Treatment Period

Participants

Time frame: 154-711 days on treatment

ArmMeasureValue (NUMBER)
AZD0837Bleeding: Number of Patients With Any Bleeding Event, During Treatment Period55 Participants
VKA, INR 2-3Bleeding: Number of Patients With Any Bleeding Event, During Treatment Period56 Participants
Secondary

Activated Partial Thromboplastin Time (APTT): Absolute Change From Baseline to End of Treatment

Median Full range, Seconds

Time frame: Baseline and End of treatment

Population: Only patients who switched to one common dose, 300 mg od, are included in the AZD0837 analysis

ArmMeasureValue (MEDIAN)
AZD0837Activated Partial Thromboplastin Time (APTT): Absolute Change From Baseline to End of Treatment12.9 sec
Secondary

Alanine Transaminase (ALAT): Number of Patients With ALAT>=3xULN, Post Baseline

ULN=Upper limit of Normal

Time frame: From baseline to Follow up

ArmMeasureValue (NUMBER)
AZD0837Alanine Transaminase (ALAT): Number of Patients With ALAT>=3xULN, Post Baseline9 Participants
VKA, INR 2-3Alanine Transaminase (ALAT): Number of Patients With ALAT>=3xULN, Post Baseline6 Participants
Secondary

AR-H067637XX, the Active Major Metabolite of AD0837: Plasma Concentration of AR-H067637XX, at End of Treatment

Time frame: 154-711 days on treatment

Population: Only patients who switched to one dose, 300 mg od, are included in the AZD0837 analysis

ArmMeasureValue (MEDIAN)
AZD0837AR-H067637XX, the Active Major Metabolite of AD0837: Plasma Concentration of AR-H067637XX, at End of Treatment341 nmol/L
Secondary

AZD0837: Plasma Concentration of AZD0837 at End of Treatment

Time frame: End of treatment

Population: Only patients who switched to one dose, 300 mg od, are included in the AZD0837 analysis

ArmMeasureValue (MEDIAN)
AZD0837AZD0837: Plasma Concentration of AZD0837 at End of Treatment675 nmol/L
Secondary

Bilirubin: Number of Patients With Bilirubin>=2xULN, Post Baseline

Time frame: From baseline to Follow up

ArmMeasureValue (NUMBER)
AZD0837Bilirubin: Number of Patients With Bilirubin>=2xULN, Post Baseline3 Participants
VKA, INR 2-3Bilirubin: Number of Patients With Bilirubin>=2xULN, Post Baseline3 Participants
Secondary

Creatinine: Absolute Change From Baseline, at End of Treatment

Time frame: Baseline and End of treatment

ArmMeasureValue (MEAN)Dispersion
AZD0837Creatinine: Absolute Change From Baseline, at End of Treatment3.70 µmol/LFull Range -67
VKA, INR 2-3Creatinine: Absolute Change From Baseline, at End of Treatment-1.17 µmol/LFull Range -56
Secondary

D-dimer:Median and Quartile Range at End of Treatment

Median (Lower Quartile-Upper Quartile ), ng/mL

Time frame: End of treatment

Population: Only patients who switched to one common dose, 300 mg od, are included in the AZD0837 analysis

ArmMeasureValue (MEDIAN)
AZD0837D-dimer:Median and Quartile Range at End of Treatment68.9 ng/mL
VKA, INR 2-3D-dimer:Median and Quartile Range at End of Treatment54.9 ng/mL
Secondary

Electroconvulsive Therapy (ECT): Absolute Change From Baseline to End of Treatment

Time frame: Baseline and End of Treatment

Population: Only patients who switched to one dose, 300 mg od, are included in the AZD0837 analysis

ArmMeasureValue (MEDIAN)
AZD0837Electroconvulsive Therapy (ECT): Absolute Change From Baseline to End of Treatment49.0 sec

Source: ClinicalTrials.gov · Data processed: Apr 2, 2026