CClinicalTrials.gg
Sign In
CompletedNCT00645853Updated Mar 23, 2012Results posted

Long-term Safety in Atrial Fibrillation Patients

A Phase 2 interventional study of AZD0837 and VKA INR 2-3 in Persistent or Permanent Nonvalvular Atrial Fibrillation, sponsored by AstraZeneca. Completed. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2012-03-23.

Sponsored by AstraZeneca · Phase 2, Interventional, and Prevention

Phase
Phase 2
Study type
Interventional
Enrollment
523
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study 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).

02

Conditions studied

  • Persistent or Permanent Nonvalvular Atrial Fibrillation

Browse trials for

03

In context

Atrial Fibrillation

3,869 studies on the registry are indexed under Atrial Fibrillation; 923 are open to participants now.

This study's enrollment of 523 is above the median of 144 across 2,380 interventional studies indexed under Atrial Fibrillation.

Browse Atrial Fibrillation studies →

Lead sponsor

AstraZeneca is the lead sponsor of 3,429 studies on the registry; 270 are open to participants now.

Of its 357 completed or terminated interventional studies of FDA-regulated products, 173 (48%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts 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

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.
05

Study design

Phase
Phase 2
Primary purpose
Prevention
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
523 participants (actual)

Study arms

  • Experimental
    1

    Drug: AZD0837

  • Active comparator
    2

    Drug: VKA INR 2-3

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

    Also known as: warfarin

06

What researchers measure

Primary outcomes

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

    Participants

    Time frame: 154-711 days on treatment

Secondary outcomes

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

    ULN=Upper limit of Normal

    Time frame: From baseline to Follow up

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

    Time frame: From baseline to Follow up

  3. Creatinine: Absolute Change From Baseline, at End of Treatment

    Time frame: Baseline and End of treatment

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

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

    Time frame: End of treatment

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

    Median Full range, Seconds

    Time frame: Baseline and End of treatment

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

    Time frame: Baseline and End of Treatment

  7. AZD0837: Plasma Concentration of AZD0837 at End of Treatment

    Time frame: End of treatment

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

    Time frame: 154-711 days on treatment

07

Results

Posted Mar 6, 2012

Participant flow

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.

Participant flow — Overall Study
MilestoneAZD0837VKA, INR 2-3
Started288235
No of patients after dose switch209188
Discontinued patient no due to closure196178
Az study closure in hungary6040
Completed196178
Not completed9257
Withdrew: Adverse event187
Withdrew: Az study closure in hungary6040
Withdrew: Withdrawal by subject52
Withdrew: Protocol violation02
Withdrew: Discontinuation criteria22
Withdrew: Recall of icf, planned operation, death74

Outcome measures

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

Participants

Time frame:
154-711 days on treatment
Reported as:
Number · Participants
Bleeding: Number of Patients With Any Bleeding Event, During Treatment Period
ParticipantsAZD0837VKA, INR 2-3
Bleeding: Number of Patients With Any Bleeding Event, During Treatment Period5556
SecondaryAlanine Transaminase (ALAT): Number of Patients With ALAT>=3xULN, Post Baseline

ULN=Upper limit of Normal

Time frame:
From baseline to Follow up
Reported as:
Number · Participants
Alanine Transaminase (ALAT): Number of Patients With ALAT>=3xULN, Post Baseline
ParticipantsAZD0837VKA, INR 2-3
Alanine Transaminase (ALAT): Number of Patients With ALAT>=3xULN, Post Baseline96
SecondaryBilirubin: Number of Patients With Bilirubin>=2xULN, Post Baseline
Time frame:
From baseline to Follow up
Reported as:
Number · Participants
Bilirubin: Number of Patients With Bilirubin>=2xULN, Post Baseline
ParticipantsAZD0837VKA, INR 2-3
Bilirubin: Number of Patients With Bilirubin>=2xULN, Post Baseline33
SecondaryCreatinine: Absolute Change From Baseline, at End of Treatment
Time frame:
Baseline and End of treatment
Reported as:
Mean · µmol/L
Creatinine: Absolute Change From Baseline, at End of Treatment
µmol/LAZD0837VKA, INR 2-3
Creatinine: Absolute Change From Baseline, at End of Treatment3.70 ± -67.0-1.17 ± -56.0
SecondaryD-dimer:Median and Quartile Range at End of Treatment

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

Time frame:
End of treatment
Reported as:
Median · ng/mL
D-dimer:Median and Quartile Range at End of Treatment
ng/mLAZD0837VKA, INR 2-3
D-dimer:Median and Quartile Range at End of Treatment68.9 (43.3 to 128.4)54.9 (31.9 to 99.0)
SecondaryActivated Partial Thromboplastin Time (APTT): Absolute Change From Baseline to End of Treatment

Median Full range, Seconds

Time frame:
Baseline and End of treatment
Reported as:
Median · sec
Activated Partial Thromboplastin Time (APTT): Absolute Change From Baseline to End of Treatment
secAZD0837
Activated Partial Thromboplastin Time (APTT): Absolute Change From Baseline to End of Treatment12.9 (-62 to 43)
SecondaryElectroconvulsive Therapy (ECT): Absolute Change From Baseline to End of Treatment
Time frame:
Baseline and End of Treatment
Reported as:
Median · sec
Electroconvulsive Therapy (ECT): Absolute Change From Baseline to End of Treatment
secAZD0837
Electroconvulsive Therapy (ECT): Absolute Change From Baseline to End of Treatment49.0 (-5 to 96)
SecondaryAZD0837: Plasma Concentration of AZD0837 at End of Treatment
Time frame:
End of treatment
Reported as:
Median · nmol/L
AZD0837: Plasma Concentration of AZD0837 at End of Treatment
nmol/LAZD0837
AZD0837: Plasma Concentration of AZD0837 at End of Treatment675 (10 to 4090)
SecondaryAR-H067637XX, the Active Major Metabolite of AD0837: Plasma Concentration of AR-H067637XX, at End of Treatment
Time frame:
154-711 days on treatment
Reported as:
Median · nmol/L
AR-H067637XX, the Active Major Metabolite of AD0837: Plasma Concentration of AR-H067637XX, at End of Treatment
nmol/LAZD0837
AR-H067637XX, the Active Major Metabolite of AD0837: Plasma Concentration of AR-H067637XX, at End of Treatment341 (10 to 929)

Adverse events

Collected over 154-711 days on treatment. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
AZD0837—73/288 (25.3%)125/288 (43.4%)
VKA INR 2-3—61/235 (26%)106/235 (45.1%)
Most frequent serious events
Showing 10 of 124
Most frequent serious events
EventAZD0837VKA INR 2-3
Cardiac FailureCardiac disorders7/2886/235
Atrial FibrillationCardiac disorders4/2884/235
Angina UnstableCardiac disorders0/2883/235
Gastrointestinal HaemorrhageGastrointestinal disorders0/2883/235
BronchitisInfections and infestations2/2883/235
PneumoniaInfections and infestations3/2883/235
BradycardiaCardiac disorders3/2882/235
ErysipelasInfections and infestations3/2881/235
Colon CancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)3/2880/235
SyncopeNervous system disorders3/2881/235
Most frequent other events
Showing 10 of 11
Most frequent other events
EventAZD0837VKA INR 2-3
DiarrhoeaGastrointestinal disorders37/28818/235
NasopharyngitisInfections and infestations35/28830/235
Oedema PeripheralGeneral disorders25/28820/235
DizzinessNervous system disorders24/28817/235
BronchitisInfections and infestations14/28818/235
FlatulenceGastrointestinal disorders20/2881/235
FatigueGeneral disorders19/2889/235
Urinary Tract InfectionInfections and infestations13/28815/235
ArthralgiaMusculoskeletal and connective tissue disorders9/28813/235
Back PainMusculoskeletal and connective tissue disorders15/28812/235

Baseline characteristics

Age Continuous
Age Continuous(Years)AZD0837VKA, INR 2-3Total
Mean69.9 (34 to 93)68.0 (33 to 86)68.95 (33 to 93)
Sex: Female, Male
Sex: Female, Male(Participants)AZD0837VKA, INR 2-3Total
Female9073163
Male198162360
08

Study locations

No study locations are listed for this record.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 23, 2012, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT00645853
Lead sponsor
AstraZeneca
Responsible party
Sponsor
First posted
Mar 28, 2008
Start date
Oct 2007
Primary completion
May 2009
Completion
May 2009
Results posted
Mar 6, 2012
Last update
Mar 23, 2012

Study contacts

Lars Hvilstedt Rasmussen, MD, PhD, FESC
principal investigator · Head of Cardiology at Heart Centre Aalborg Aarhus University Hospital DK 9100 Aalborg Denmark

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Mar 2012. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Atrial Fibrillation→

Other studies from this sponsor

AstraZeneca

Start the discussion