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

NCT ID: NCT03061006

Last Updated: 2021-09-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 101 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-04-03
• Study Completion Date: 2021-03-15

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.

Conditions

Dementia; Cognition Disorders; Cerebral Ischemic Events

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Dabigatran Etexilate

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

Group Type: EXPERIMENTAL

Dabigatran Etexilate

Intervention Type: DRUG

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

Warfarin

Dose-adjusted warfarin (INR: 2.0-3.0)

Group Type: ACTIVE_COMPARATOR

Warfarin

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: DRUG

Warfarin

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

Intervention Type: DRUG

Other Intervention Names

Pradaxa; Coumadin

Eligibility Criteria

Inclusion Criteria

1. Male or female >65 years of age.

2. Non-valvular atrial fibrillation documented by electrocardiogram, ambulatory event monitor, or telemetry within 12 months of enrollment.

3. Moderate risk of thromboembolism based upon a CHADS score or CHADS2 Vasc score of ≥2.

4. Ability to complete a mini-mental status evaluation.

5. Ability to independently comprehend and complete a quality of life and dementia questionnaires.

6. Ability to provide informed consent for study participation.

7. Willing and able to comply with the prescribed follow-up tests and schedule of evaluations.

10. Participation in any other clinical trials involving investigational or marketed products within 30 days prior to entry in the study.

11. 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.

12. Concurrent pharmacologic treatment that is required to treat a condition long-term in which concurrent use of dabigatran etexilate is contraindicated.

13. 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

14. The Principal Investigator(s) determine(s) that the subject is not eligible for participation in this research study.

Exclusion Criteria

1. Inability to take an anticoagulant due to known or perceived bleeding risk.

2. Known coagulopathy that may impact the choice, duration, efficacy and safety of anticoagulation therapy.

3. 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.

4. Severe renal dysfunction, defined as a creatinine clearance rate <15 mL/min (documented within the last 3 months).

5. History of any form of dementia.

6. A life expectancy less than 24 months.

7. Inability to comply with the follow-up schedule.

8. Current participation in a clinical investigation that includes an active pharmacologic treatment arm.

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: collaborator

Intermountain Health Care, Inc.

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Intermountain Heart Institute

Murray, Utah, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 35833913 (View on PubMed)

Other Identifiers

1050164

Identifier Type: -

Identifier Source: org_study_id