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Long-term Safety in Atrial Fibrillation Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00645853
Recruitment Status : Completed
First Posted : March 28, 2008
Results First Posted : March 6, 2012
Last Update Posted : March 23, 2012
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Prevention
Condition Persistent or Permanent Nonvalvular Atrial Fibrillation
Interventions Drug: AZD0837
Drug: VKA INR 2-3
Enrollment 523
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
Arm/Group Title AZD0837 VKA, INR 2-3
Hide Arm/Group Description 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. Vitamin K antagonists (VKA), titrated to an international normalised ratio (INR) of 2.0 to 3.0 with a target value of 2.5
Period Title: Overall Study
Started 288 235
No of Patients After Dose Switch 209 [1] 188 [2]
Discontinued Patient No Due to Closure 196 [3] 178 [3]
AZ Study Closure in Hungary 60 40
Completed 196 178
Not Completed 92 57
Reason Not Completed
Adverse Event             18             7
AZ study closure in Hungary             60             40
Withdrawal by Subject             5             2
Protocol Violation             0             2
Discontinuation criteria             2             2
recall of ICF, planned operation, death             7             4
[1]
All patients in the AZD0837 arm switched from their initial doses, to a general dose of 300 mg od
[2]
No changes for VKA patients
[3]
No of patients discontinued due the study termination caused tablet formulation stability problems
Arm/Group Title AZD0837 VKA, INR 2-3 Total
Hide Arm/Group Description 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. Vitamin K antagonists (VKA), titrated to an international normalised ratio (INR) of 2.0 to 3.0 with a target value of 2.5 Total of all reporting groups
Overall Number of Baseline Participants 288 235 523
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 288 participants 235 participants 523 participants
69.9
(34 to 93)
68.0
(33 to 86)
68.95
(33 to 93)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 288 participants 235 participants 523 participants
Female
90
  31.3%
73
  31.1%
163
  31.2%
Male
198
  68.8%
162
  68.9%
360
  68.8%
1.Primary Outcome
Title Bleeding: Number of Patients With Any Bleeding Event, During Treatment Period
Hide Description Participants
Time Frame 154-711 days on treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title AZD0837 VKA, INR 2-3
Hide Arm/Group Description:
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.
Vitamin K antagonists (VKA), titrated to an international normalised ratio (INR) of 2.0 to 3.0 with a target value of 2.5
Overall Number of Participants Analyzed 288 235
Measure Type: Number
Unit of Measure: Participants
55 56
2.Secondary Outcome
Title Alanine Transaminase (ALAT): Number of Patients With ALAT>=3xULN, Post Baseline
Hide Description ULN=Upper limit of Normal
Time Frame From baseline to Follow up
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title AZD0837 VKA, INR 2-3
Hide Arm/Group Description:
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.
Vitamin K antagonists (VKA), titrated to an international normalised ratio (INR) of 2.0 to 3.0 with a target value of 2.5
Overall Number of Participants Analyzed 288 235
Measure Type: Number
Unit of Measure: Participants
9 6
3.Secondary Outcome
Title Bilirubin: Number of Patients With Bilirubin>=2xULN, Post Baseline
Hide Description [Not Specified]
Time Frame From baseline to Follow up
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title AZD0837 VKA, INR 2-3
Hide Arm/Group Description:
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.
Vitamin K antagonists (VKA), titrated to an international normalised ratio (INR) of 2.0 to 3.0 with a target value of 2.5
Overall Number of Participants Analyzed 288 235
Measure Type: Number
Unit of Measure: Participants
3 3
4.Secondary Outcome
Title Creatinine: Absolute Change From Baseline, at End of Treatment
Hide Description [Not Specified]
Time Frame Baseline and End of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title AZD0837 VKA, INR 2-3
Hide Arm/Group Description:
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.
Vitamin K antagonists (VKA), titrated to an international normalised ratio (INR) of 2.0 to 3.0 with a target value of 2.5
Overall Number of Participants Analyzed 288 235
Mean (Full Range)
Unit of Measure: µmol/L
3.70
(-67.0 to 120.0)
-1.17
(-56.0 to 116)
5.Secondary Outcome
Title D-dimer:Median and Quartile Range at End of Treatment
Hide Description Median (Lower Quartile-Upper Quartile ), ng/mL
Time Frame End of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Only patients who switched to one common dose, 300 mg od, are included in the AZD0837 analysis
Arm/Group Title AZD0837 VKA, INR 2-3
Hide Arm/Group Description:
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.
Vitamin K antagonists (VKA), titrated to an international normalised ratio (INR) of 2.0 to 3.0 with a target value of 2.5
Overall Number of Participants Analyzed 193 232
Median (Inter-Quartile Range)
Unit of Measure: ng/mL
68.9
(43.3 to 128.4)
54.9
(31.9 to 99.0)
6.Secondary Outcome
Title Activated Partial Thromboplastin Time (APTT): Absolute Change From Baseline to End of Treatment
Hide Description Median Full range, Seconds
Time Frame Baseline and End of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Only patients who switched to one common dose, 300 mg od, are included in the AZD0837 analysis
Arm/Group Title AZD0837
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 173
Median (Full Range)
Unit of Measure: sec
12.9
(-62 to 43)
7.Secondary Outcome
Title Electroconvulsive Therapy (ECT): Absolute Change From Baseline to End of Treatment
Hide Description [Not Specified]
Time Frame Baseline and End of Treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Only patients who switched to one dose, 300 mg od, are included in the AZD0837 analysis
Arm/Group Title AZD0837
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 129
Median (Full Range)
Unit of Measure: sec
49.0
(-5 to 96)
8.Secondary Outcome
Title AZD0837: Plasma Concentration of AZD0837 at End of Treatment
Hide Description [Not Specified]
Time Frame End of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Only patients who switched to one dose, 300 mg od, are included in the AZD0837 analysis
Arm/Group Title AZD0837
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 195
Median (Full Range)
Unit of Measure: nmol/L
675
(10 to 4090)
9.Secondary Outcome
Title AR-H067637XX, the Active Major Metabolite of AD0837: Plasma Concentration of AR-H067637XX, at End of Treatment
Hide Description [Not Specified]
Time Frame 154-711 days on treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Only patients who switched to one dose, 300 mg od, are included in the AZD0837 analysis
Arm/Group Title AZD0837
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 195
Median (Full Range)
Unit of Measure: nmol/L
341
(10 to 929)
Time Frame 154-711 days on treatment
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title AZD0837 VKA INR 2-3
Hide Arm/Group Description 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 Vitamin K antagonists (VKA), titrated to an international normalised ratio (INR) of 2.0 to 3.0 with a target value of 2.5
All-Cause Mortality
AZD0837 VKA INR 2-3
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
AZD0837 VKA INR 2-3
Affected / at Risk (%) Affected / at Risk (%)
Total   73/288 (25.35%)   61/235 (25.96%) 
Blood and lymphatic system disorders     
Neutropenia † 1  1/288 (0.35%)  0/235 (0.00%) 
Cardiac disorders     
Cardiac Failure † 1  7/288 (2.43%)  6/235 (2.55%) 
Atrial Fibrillation † 1  4/288 (1.39%)  4/235 (1.70%) 
Angina Unstable † 1  0/288 (0.00%)  3/235 (1.28%) 
Bradycardia † 1  3/288 (1.04%)  2/235 (0.85%) 
Angina Pectoris † 1  2/288 (0.69%)  1/235 (0.43%) 
Sick Sinus Syndrome † 1  2/288 (0.69%)  1/235 (0.43%) 
Acute Coronary Syndrome † 1  0/288 (0.00%)  1/235 (0.43%) 
Atrial Flutter † 1  0/288 (0.00%)  1/235 (0.43%) 
Bradyarrhythmia † 1  0/288 (0.00%)  1/235 (0.43%) 
Cardiac Failure Congestive † 1  1/288 (0.35%)  0/235 (0.00%) 
Chordae Tendinae Rupture † 1  0/288 (0.00%)  1/235 (0.43%) 
Coronary Artery Stenosis † 1  1/288 (0.35%)  0/235 (0.00%) 
Heart Valve Incompetence † 1  1/288 (0.35%)  0/235 (0.00%) 
Myocardial Ischaemia † 1  0/288 (0.00%)  1/235 (0.43%) 
Palpitations † 1  0/288 (0.00%)  1/235 (0.43%) 
Tachyarrhythmia † 1  0/288 (0.00%)  1/235 (0.43%) 
Tachycardia † 1  1/288 (0.35%)  1/235 (0.43%) 
Ventricular Tachycardia † 1  0/288 (0.00%)  1/235 (0.43%) 
Endocrine disorders     
Hyperthyroidism † 1  1/288 (0.35%)  0/235 (0.00%) 
Eye disorders     
Cataract † 1  1/288 (0.35%)  2/235 (0.85%) 
Eye Haemorrhage † 1  0/288 (0.00%)  1/235 (0.43%) 
Glaucoma † 1  0/288 (0.00%)  1/235 (0.43%) 
Retinal Artery Embolism † 1  1/288 (0.35%)  0/235 (0.00%) 
Gastrointestinal disorders     
Gastrointestinal Haemorrhage † 1  0/288 (0.00%)  3/235 (1.28%) 
Gastric Ulcer † 1  0/288 (0.00%)  2/235 (0.85%) 
Abdominal Hernia † 1  1/288 (0.35%)  0/235 (0.00%) 
Abdominal Pain † 1  0/288 (0.00%)  1/235 (0.43%) 
Abdominal Pain Lower † 1  0/288 (0.00%)  1/235 (0.43%) 
Anal Haemorrhage † 1  1/288 (0.35%)  0/235 (0.00%) 
Anal Ulcer † 1  0/288 (0.00%)  1/235 (0.43%) 
Diarrhoea † 1  0/288 (0.00%)  1/235 (0.43%) 
Gastritis † 1  0/288 (0.00%)  1/235 (0.43%) 
Haematemesis † 1  0/288 (0.00%)  1/235 (0.43%) 
Inguinal Hernia † 1  1/288 (0.35%)  1/235 (0.43%) 
Melaena † 1  0/288 (0.00%)  1/235 (0.43%) 
Nausea † 1  1/288 (0.35%)  0/235 (0.00%) 
Periodontal Disease † 1  0/288 (0.00%)  1/235 (0.43%) 
General disorders     
Death † 1  2/288 (0.69%)  0/235 (0.00%) 
Non-Cardiac Chest Pain † 1  0/288 (0.00%)  2/235 (0.85%) 
Asthenia † 1  1/288 (0.35%)  0/235 (0.00%) 
Hepatobiliary disorders     
Cholecystitis Chronic † 1  0/288 (0.00%)  1/235 (0.43%) 
Cholelithiasis † 1  0/288 (0.00%)  1/235 (0.43%) 
Jaundice Cholestatic † 1  0/288 (0.00%)  1/235 (0.43%) 
Immune system disorders     
Corneal Graft Rejection † 1  0/288 (0.00%)  1/235 (0.43%) 
Infections and infestations     
Bronchitis † 1  2/288 (0.69%)  3/235 (1.28%) 
Erysipelas † 1  3/288 (1.04%)  1/235 (0.43%) 
Pneumonia † 1  3/288 (1.04%)  3/235 (1.28%) 
Abscess Limb † 1  1/288 (0.35%)  0/235 (0.00%) 
Endocarditis † 1  0/288 (0.00%)  1/235 (0.43%) 
Gastroenteritis † 1  1/288 (0.35%)  1/235 (0.43%) 
Intervertebral Discitis † 1  0/288 (0.00%)  1/235 (0.43%) 
Laryngitis † 1  1/288 (0.35%)  0/235 (0.00%) 
Pyelonephritis † 1  1/288 (0.35%)  0/235 (0.00%) 
Respiratory Tract Infection † 1  1/288 (0.35%)  0/235 (0.00%) 
Sinusitis † 1  1/288 (0.35%)  0/235 (0.00%) 
Urinary Tract Infection † 1  0/288 (0.00%)  1/235 (0.43%) 
Urosepsis † 1  0/288 (0.00%)  1/235 (0.43%) 
Injury, poisoning and procedural complications     
Concussion † 1  0/288 (0.00%)  1/235 (0.43%) 
Contusion † 1  0/288 (0.00%)  1/235 (0.43%) 
Foreign Body Trauma † 1  0/288 (0.00%)  1/235 (0.43%) 
Head Injury † 1  0/288 (0.00%)  1/235 (0.43%) 
Joint Dislocation † 1  1/288 (0.35%)  0/235 (0.00%) 
Post Procedural Haemorrhage † 1  0/288 (0.00%)  1/235 (0.43%) 
Subdural Haematoma † 1  0/288 (0.00%)  1/235 (0.43%) 
Tibia Fracture † 1  1/288 (0.35%)  0/235 (0.00%) 
Investigations     
Alanine Aminotransferase Increased † 1  2/288 (0.69%)  1/235 (0.43%) 
Haemoglobin Decreased † 1  1/288 (0.35%)  2/235 (0.85%) 
Blood Alkaline Phosphatase Increased † 1  0/288 (0.00%)  1/235 (0.43%) 
Blood Glucose Increased † 1  0/288 (0.00%)  1/235 (0.43%) 
International Normalised Ratio Increased † 1  0/288 (0.00%)  1/235 (0.43%) 
Metabolism and nutrition disorders     
Diabetes Mellitus † 1  2/288 (0.69%)  1/235 (0.43%) 
Dehydration † 1  1/288 (0.35%)  1/235 (0.43%) 
Hyperkalaemia † 1  1/288 (0.35%)  0/235 (0.00%) 
Hypoglycaemia † 1  1/288 (0.35%)  0/235 (0.00%) 
Musculoskeletal and connective tissue disorders     
Arthritis † 1  0/288 (0.00%)  2/235 (0.85%) 
Osteoarthritis † 1  2/288 (0.69%)  0/235 (0.00%) 
Arthralgia † 1  1/288 (0.35%)  0/235 (0.00%) 
Back Pain † 1  1/288 (0.35%)  1/235 (0.43%) 
Bursitis † 1  1/288 (0.35%)  0/235 (0.00%) 
Inguinal Mass † 1  0/288 (0.00%)  1/235 (0.43%) 
Muscle Atrophy † 1  0/288 (0.00%)  1/235 (0.43%) 
Muscular Weakness † 1  1/288 (0.35%)  0/235 (0.00%) 
Myalgia † 1  0/288 (0.00%)  1/235 (0.43%) 
Osteitis † 1  1/288 (0.35%)  0/235 (0.00%) 
Rheumatoid Arthritis † 1  0/288 (0.00%)  1/235 (0.43%) 
Scleroderma † 1  1/288 (0.35%)  0/235 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Colon Cancer † 1  3/288 (1.04%)  0/235 (0.00%) 
Basal Cell Carcinoma † 1  1/288 (0.35%)  0/235 (0.00%) 
Colon Adenoma † 1  0/288 (0.00%)  1/235 (0.43%) 
Colon Cancer Metastatic † 1  0/288 (0.00%)  1/235 (0.43%) 
Metastases To Central Nervous System † 1  1/288 (0.35%)  0/235 (0.00%) 
Nervous system disorders     
Syncope † 1  3/288 (1.04%)  1/235 (0.43%) 
Headache † 1  0/288 (0.00%)  2/235 (0.85%) 
Transient Ischaemic Attack † 1  1/288 (0.35%)  2/235 (0.85%) 
Cerebral Artery Embolism † 1  0/288 (0.00%)  1/235 (0.43%) 
Cerebrovascular Accident † 1  1/288 (0.35%)  1/235 (0.43%) 
Dizziness † 1  1/288 (0.35%)  1/235 (0.43%) 
Encephalitis † 1  1/288 (0.35%)  0/235 (0.00%) 
Epilepsy † 1  1/288 (0.35%)  0/235 (0.00%) 
Ischaemic Stroke † 1  1/288 (0.35%)  0/235 (0.00%) 
Status Epilepticus † 1  1/288 (0.35%)  0/235 (0.00%) 
Vascular Encephalopathy † 1  1/288 (0.35%)  0/235 (0.00%) 
Vertebrobasilar Insufficiency † 1  1/288 (0.35%)  0/235 (0.00%) 
Psychiatric disorders     
Delusional Disorder, Persecutory Type † 1  1/288 (0.35%)  0/235 (0.00%) 
Dysthymic Disorder † 1  1/288 (0.35%)  0/235 (0.00%) 
Renal and urinary disorders     
Haematuria † 1  2/288 (0.69%)  1/235 (0.43%) 
Dysuria † 1  1/288 (0.35%)  0/235 (0.00%) 
Renal Failure † 1  1/288 (0.35%)  0/235 (0.00%) 
Urinary Bladder Haemorrhage † 1  0/288 (0.00%)  1/235 (0.43%) 
Reproductive system and breast disorders     
Postmenopausal Haemorrhage † 1  1/288 (0.35%)  0/235 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea † 1  2/288 (0.69%)  1/235 (0.43%) 
Dyspnoea Exertional † 1  1/288 (0.35%)  0/235 (0.00%) 
Haemoptysis † 1  0/288 (0.00%)  1/235 (0.43%) 
Pleural Effusion † 1  1/288 (0.35%)  1/235 (0.43%) 
Skin and subcutaneous tissue disorders     
Rash † 1  0/288 (0.00%)  1/235 (0.43%) 
Vascular disorders     
Arterial Occlusive Disease † 1  1/288 (0.35%)  0/235 (0.00%) 
Arterial Stenosis Limb † 1  1/288 (0.35%)  0/235 (0.00%) 
Hypertension † 1  1/288 (0.35%)  0/235 (0.00%) 
Orthostatic Hypotension † 1  1/288 (0.35%)  0/235 (0.00%) 
Peripheral Artery Aneurysm † 1  1/288 (0.35%)  0/235 (0.00%) 
Peripheral Embolism † 1  1/288 (0.35%)  0/235 (0.00%) 
Subclavian Vein Thrombosis † 1  1/288 (0.35%)  0/235 (0.00%) 
800003Varicose Vein † 1  1/288 (0.35%)  0/235 (0.00%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 10.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
AZD0837 VKA INR 2-3
Affected / at Risk (%) Affected / at Risk (%)
Total   125/288 (43.40%)   106/235 (45.11%) 
Gastrointestinal disorders     
Diarrhoea † 1  37/288 (12.85%)  18/235 (7.66%) 
Flatulence † 1  20/288 (6.94%)  1/235 (0.43%) 
General disorders     
Oedema Peripheral † 1  25/288 (8.68%)  20/235 (8.51%) 
Fatigue † 1  19/288 (6.60%)  9/235 (3.83%) 
Infections and infestations     
Nasopharyngitis † 1  35/288 (12.15%)  30/235 (12.77%) 
Bronchitis † 1  14/288 (4.86%)  18/235 (7.66%) 
Urinary Tract Infection † 1  13/288 (4.51%)  15/235 (6.38%) 
Injury, poisoning and procedural complications     
Fall † 1  4/288 (1.39%)  12/235 (5.11%) 
Musculoskeletal and connective tissue disorders     
Back Pain † 1  15/288 (5.21%)  12/235 (5.11%) 
Arthralgia † 1  9/288 (3.13%)  13/235 (5.53%) 
Nervous system disorders     
Dizziness † 1  24/288 (8.33%)  17/235 (7.23%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 10.0
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Gerard Lynch
Organization: AstraZeneca
EMail: aztrial_results_posting@astrazeneca.com
Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00645853     History of Changes
Other Study ID Numbers: D1250C00042
First Submitted: March 19, 2008
First Posted: March 28, 2008
Results First Submitted: June 30, 2011
Results First Posted: March 6, 2012
Last Update Posted: March 23, 2012