CAF: Impact of Anticoagulation Therapy on the Cognitive Decline and Dementia in Patients With Non-Valvular Atrial Fibrillation
Study Details
Study Description
Brief Summary
Patients will be screened at Intermountain Medical Center and at Intermountain-affiliated anticoagulation clinics in the Salt Lake City region. Patients with non-valvular atrial fibrillation will be considered for study. After written informed consent is obtained, subjects who meet eligibility criteria will be randomized 1:1 to 2 treatment arms: Group 1: Dabigatran etexilate (150 mg BID if CrCL > 30 mL/min, or 75 mg BID if CrCL > 15 to 30 mL/min or per USPI; and Group 2: Warfarin (Dose-adjusted (INR 2.0 - 3.0). Assessment of kidney function every 6 months will be done for Group 1. Standard warfarin follow-up and education, based upon system criteria, will be done for Group 2. All subjects will be followed for 24 months, and will be assessed at 1-week, then 3-, 6-, 12-, 18- and 24-months post-anticoagulation visits as well as other visits deem necessary for clinical care. All subjects will undergo protocol-specified laboratory tests and will complete 6 standard, validated questionnaires at each follow-up visit following the week 1 visit, except at the 3-month visit when only one questionnaire will be administered. To determine brain volume and characteristic changes representative of micro-bleeding, the first 10 subjects in each treatment group who are willing and able to undergo the procedure will participate in a MRI sub-study. The cranial MRI will be done at baseline and at 24-months post-anticoagulation on this sub-group.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 4 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Dabigatran Etexilate 150 mg BID (CrCL > 30 mL/min) or 75 mg BID (CrCL 15-30 mL/min) |
Drug: Dabigatran Etexilate
150 mg BID (CrCL > 30 mL/min) or 75 mg BID (CrCL > 15 to 30 mL/min); Assessment of kidney function every 6 months.
Other Names:
|
Active Comparator: Warfarin Dose-adjusted warfarin (INR: 2.0-3.0) |
Drug: Warfarin
Dose-adjusted (INR 2.0 - 3.0); Standard warfarin follow-up and education based upon system criteria.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Incident dementia determined by a formal diagnosis of dementia by a neurologist [24 months]
Incident dementia will be determined by a formal diagnosis of dementia by a neurologist
- Moderate decline in cognitive function based on results of the Alzheimer's Disease Assessment Scale and the Disability Assessment for Dementia. [24 months]
Determined by measuring the change from baseline to study conclusion on the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog11, with scores ranging from 0 to 70, and higher scores indicating greater impairment) and the Disability Assessment for Dementia (DAD, with scores ranging from 0 to 100, and higher scores indicating less impairment). An increase in ADAS-cog11 of >30% is considered significant for moderate cognitive decline. In subjects that score <50% on the DAD, there is a direct correlation with global deterioration scales and scores. Subjects with a 30% decrease in DAD score or those with a score <50% will be considered to have moderate cognitive decline. These scores will be aggregated and if a patient meets either one of the cognitive decline definitions they will be deemed positive for cognitive impairment.
Secondary Outcome Measures
- Stroke or Transient ischemic attack (TIA), intracranial bleed [24 months]
- Changes from baseline scores on the mini-mental status evaluation and the Hachinski Ischemic Scale. [24 months]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male or female >65 years of age.
-
Non-valvular atrial fibrillation documented by electrocardiogram, ambulatory event monitor, or telemetry within 12 months of enrollment.
-
Moderate risk of thromboembolism based upon a CHADS score or CHADS2 Vasc score of ≥2.
-
Ability to complete a mini-mental status evaluation.
-
Ability to independently comprehend and complete a quality of life and dementia questionnaires.
-
Ability to provide informed consent for study participation.
-
Willing and able to comply with the prescribed follow-up tests and schedule of evaluations.
Exclusion Criteria:
-
Inability to take an anticoagulant due to known or perceived bleeding risk.
-
Known coagulopathy that may impact the choice, duration, efficacy and safety of anticoagulation therapy.
-
Atrial Fibrillation in the setting of valvular heart disease. Valvular heart disease defined as any surgical valve, mitral stenosis, or moderate-severe valvular heart disease.
-
Severe renal dysfunction, defined as a creatinine clearance rate <15 mL/min (documented within the last 3 months).
-
History of any form of dementia.
-
A life expectancy less than 24 months.
-
Inability to comply with the follow-up schedule.
-
Current participation in a clinical investigation that includes an active pharmacologic treatment arm.
-
An upper age limit not to be used if participation inclusion criteria are met.
-
Participation in any other clinical trials involving investigational or marketed products within 30 days prior to entry in the study.
-
Other conditions that in the opinion of the Principal Investigator(s) may increase risk to the subject and/or compromise the quality of the clinical trial.
-
Concurrent pharmacologic treatment that is required to treat a condition long-term in which concurrent use of dabigatran etexilate is contraindicated.
-
Treatment with any anticoagulant drug for stroke prevention for more than 30 days.
-
Aspirin and P2Y12 inhibitors (e.g. clopidogrel (Plavix), or prasugrel (Effient)) are not considered anticoagulant drugs.
-
If the subject has received any anticoagulant drug for stroke prevention for less than 30 days, the Principal Investigator(s) or a Co-Investigator will decide whether or not the subject is eligible for this study
- The Principal Investigator(s) determine(s) that the subject is not eligible for participation in this research study.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Intermountain Heart Institute | Murray | Utah | United States | 84143 |
Sponsors and Collaborators
- Intermountain Health Care, Inc.
- Boehringer Ingelheim
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 1050164