Impact of Anticoagulation Therapy on the Cognitive Decline and Dementia in Patients With Non-Valvular Atrial Fibrillation (CAF Trial)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 101
- 试验地点
- 1
- 主要终点
- Number of Participants With Incident Dementia Determined by a Formal Diagnosis of Dementia by a Neurologist
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 ≥
- •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.
排除标准
- •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.
研究组 & 干预措施
Dabigatran Etexilate
150 mg BID (CrCL > 30 mL/min) or 75 mg BID (CrCL 15-30 mL/min)
干预措施: Dabigatran Etexilate (Drug)
Warfarin
Dose-adjusted warfarin (INR: 2.0-3.0)
干预措施: Warfarin (Drug)
结局指标
主要结局
Number of Participants With Incident Dementia Determined by a Formal Diagnosis of Dementia by a Neurologist
时间窗: 24 months
Incident dementia will be determined by a formal diagnosis of dementia by a neurologist
Number of Participants With Moderate Decline in Cognitive Function Based on Results of the Alzheimer's Disease Assessment Scale and the Disability Assessment for Dementia.
时间窗: 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.
次要结局
- Number of Participants With Stroke or Transient Ischemic Attack (TIA) or Intracranial Bleed(24 months)
- Percent Change From Baseline in Mini-Mental State Examination Scores.(24 months)
- Changes From Baseline Scores on the Hachinski Ischemic Scale(24 months)