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Impact of Anticoagulation Therapy on the Cognitive Decline and Dementia in Patients With Non-Valvular Atrial Fibrillation (CAF)

Primary Purpose

Dementia, Cognition Disorders, Cerebral Ischemic Events

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Dabigatran Etexilate

Warfarin

About this trial

This is an interventional other trial for Dementia

Eligibility Criteria

65 Years - undefined (Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Intermountain Heart Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Dabigatran Etexilate

Warfarin

Arm Description

150 mg BID (CrCL > 30 mL/min) or 75 mg BID (CrCL 15-30 mL/min)

Dose-adjusted warfarin (INR: 2.0-3.0)

Outcomes

Primary Outcome Measures

Incident dementia determined by a formal diagnosis of dementia by a neurologist

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.

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

Changes from baseline scores on the mini-mental status evaluation and the Hachinski Ischemic Scale.

Full Information

NCT ID

NCT03061006

First Posted

February 9, 2017

Last Updated

August 30, 2021

Sponsor

Intermountain Health Care, Inc.

Collaborators

Boehringer Ingelheim

1. Study Identification

Unique Protocol Identification Number

NCT03061006

Brief Title

Impact of Anticoagulation Therapy on the Cognitive Decline and Dementia in Patients With Non-Valvular Atrial Fibrillation

Acronym

CAF

Official Title

Impact of Anticoagulation Therapy on the Cognitive Decline and Dementia in Patients With Non-Valvular Atrial Fibrillation (CAF Trial)

Study Type

Interventional

2. Study Status

Record Verification Date

August 2021

Overall Recruitment Status

Completed

Study Start Date

April 3, 2017 (Actual)

Primary Completion Date

March 15, 2021 (Actual)

Study Completion Date

March 15, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Intermountain Health Care, Inc.

Collaborators

Boehringer Ingelheim

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Dementia, Cognition Disorders, Cerebral Ischemic Events

7. Study Design

Primary Purpose

Other

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

101 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Dabigatran Etexilate

Arm Type

Experimental

Arm Description

150 mg BID (CrCL > 30 mL/min) or 75 mg BID (CrCL 15-30 mL/min)

Arm Title

Warfarin

Arm Type

Active Comparator

Arm Description

Dose-adjusted warfarin (INR: 2.0-3.0)

Intervention Type

Drug

Intervention Name(s)

Dabigatran Etexilate

Other Intervention Name(s)

Pradaxa

Intervention Description

150 mg BID (CrCL > 30 mL/min) or 75 mg BID (CrCL > 15 to 30 mL/min); Assessment of kidney function every 6 months.

Intervention Type

Drug

Intervention Name(s)

Warfarin

Other Intervention Name(s)

Coumadin

Intervention Description

Dose-adjusted (INR 2.0 - 3.0); Standard warfarin follow-up and education based upon system criteria.

Primary Outcome Measure Information:

Title

Incident dementia determined by a formal diagnosis of dementia by a neurologist

Description

Incident dementia will be determined by a formal diagnosis of dementia by a neurologist

Time Frame

24 months

Title

Moderate decline in cognitive function based on results of the Alzheimer's Disease Assessment Scale and the Disability Assessment for Dementia.

Description

Time Frame

24 months

Secondary Outcome Measure Information:

Title

Stroke or Transient ischemic attack (TIA), intracranial bleed

Time Frame

24 months

Title

Changes from baseline scores on the mini-mental status evaluation and the Hachinski Ischemic Scale.

Time Frame

24 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility 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.

Facility Information:

Facility Name

Intermountain Heart Institute

City

Murray

State/Province

Utah

ZIP/Postal Code

84143

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

35833913

Citation

Kwan J, Hafdi M, Chiang LLW, Myint PK, Wong LS, Quinn TJ. Antithrombotic therapy to prevent cognitive decline in people with small vessel disease on neuroimaging but without dementia. Cochrane Database Syst Rev. 2022 Jul 14;7(7):CD012269. doi: 10.1002/14651858.CD012269.pub2.

Results Reference

derived

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Impact of Anticoagulation Therapy on the Cognitive Decline and Dementia in Patients With Non-Valvular Atrial Fibrillation

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