Comparing the Safety and Efficacy of Apixaban and Rivaroxaban

NCT ID: NCT06953726

Last Updated: 2025-05-01

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 10000 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-06-02
• Study Completion Date: 2033-10-03

Brief Summary

• The trial will compare two anticoagulants ("blood thinners") that are currently used in the VA and are considered standard care to prevent strokes in patients with atrial fibrillation. The two most commonly-used anticoagulants will be compared: apixaban (Eliquis) and rivaroxaban (Xarelto). They are considered by many doctors to have similar benefits and risks, but no one knows for sure.
• The trial only enrolls patients with a diagnosis of atrial fibrillation ("A Fib").
• We will measure, in about 10,000 VA patients nationally, whether the rates of stroke, major bleeding, or death differ between these two drugs.
• The trial will last about 7 years, but after the first prescription, all information will be collected from electronic medical records.

Detailed Description

The study hypothesis is that apixaban will be superior to rivaroxaban with respect to safety using the International Society of Thrombosis and Haemostasis (ISTH) definition of major bleeding and at least non-inferior with respect to efficacy among patients with atrial fibrillation (AF) or atrial flutter (AFL), henceforth noted collectively as "AF". This pragmatic, point-of-care trial will enroll approximately 10,000 Veterans >=age 65 years with AF and a CHA2DS2-VASc score >=3 and randomize them to receive apixaban or rivaroxaban in a 1:1 allocation.

Co-Primary Objectives: Determine in VA trial participants >=age 65 years with non-valvular AF whether oral anticoagulation with apixaban is:

1. Superior to rivaroxaban for the composite safety outcome of ISTH major bleeding

2. Non-inferior to rivaroxaban for the composite efficacy outcome of ischemic stroke, systemic embolism, or all-cause death

Secondary Objectives:

1. Determine in VA trial participants with non-valvular AF whether oral anticoagulation with apixaban is superior to rivaroxaban for the composite efficacy outcome of ischemic stroke, systemic embolism, or all-cause death.

2. Assess impact of anticoagulant therapy on hospitalization for: heart failure, myocardial infarction, or acute coronary syndromes/unstable angina.

3. Examine each component of the composite efficacy endpoint individually (ischemic stroke, systemic embolism, all-cause mortality).

Co-Primary Endpoints:

1. Time to first ISTH-defined major bleeding (Superiority Hypothesis)

2. Time to first ischemic stroke, systemic embolism, or all-cause mortality (Non-Inferiority Hypothesis)

Secondary Endpoints (hierarchically ranked):

1. Time to first ischemic stroke, systemic embolism, or all-cause mortality (Superiority Hypothesis)

2. Time to first ischemic stroke

3. Time to first hospitalization for heart failure, myocardial infarction, or acute coronary syndrome

4. Time to first systemic embolism

5. Time to all-cause death

The estimated number of enrollees will be 10,000 Veterans from approximately 100 VA Medical Centers throughout the U.S.; broad geographical representation in every region is anticipated. Efforts will be made to recruit female Veterans as well as Veterans from diverse racial and ethnic backgrounds with representation of both academic tertiary urban centers and rural community-based outpatient clinics (CBOCs). Strong consideration will be given to selecting enrolling sites based on their prior experience with ambulatory cardiac monitors and, in particular, the 14-day patch monitor (Ziopatch XT), since sites must participate in both the Screening and Treatment Trials. The study will not include enrolling sites outside the U.S.

The primary analysis will comprise Veterans >=65 years, with AF or atrial flutter and CHA2DS2-VASc score >=3. Patients already taking OACs (warfarin or any DOAC) for AF will be eligible. Those on single or dual antiplatelet agents will also be eligible.

Study participants will be randomized to twice daily oral administration of apixaban 5mg or daily oral administration of rivaroxaban 20mg. Reduced dose apixaban (2.5 mg twice daily) will be given to participants who meet 2 of the 3 criteria: age 80 years, body weight 60 kg, and serum creatinine 1.5 mg/dL. Reduced dose rivaroxaban (15 mg once daily) will be given to participants with a creatinine clearance 15-50 mL/min.

The study is planned for 3 years of active enrollment and at least 3 years of remote follow-up of the last enrolled participant, thus 6 years of data collection, with an additional year to completion of data analysis: 7 years (84 months) total.

Enrollment and initiation of anticoagulant will take less than one month for most patients, and up to 90 days for patients randomized to switch to a different OAC who recently received a 90-day supply of their current medication. After randomization to either apixaban or rivaroxaban, all clinical management is per the participants' providers, and all electronic data are collected remotely.

Conditions

Atrial Fibrillation

Study Design

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

Study Groups

Apixaban Arm

Study participants will be randomized to twice daily oral administration of apixaban 5mg. Reduced dose apixaban (2.5 mg twice daily) will be given to participants who meet 2 of the 3 criteria: age 80 years, body weight 60 kg, and serum creatinine 1.5 mg/dL.

Group Type: ACTIVE_COMPARATOR

Apixaban

Intervention Type: DRUG

Study participants will be randomized to twice daily oral administration of apixaban 5mg. Reduced dose apixaban (2.5 mg twice daily) will be given to participants who meet 2 of the 3 criteria: age 80 years, body weight 60 kg, and serum creatinine 1.5 mg/dL.

Rivaroxaban Arm

Study participants will be randomized to daily oral administration of rivaroxaban 20mg. Reduced dose rivaroxaban (15 mg once daily) will be given to participants with a creatinine clearance 15-50 mL/min.

Group Type: ACTIVE_COMPARATOR

Rivaroxaban

Intervention Type: DRUG

Study participants will be randomized to daily oral administration of rivaroxaban 20mg. Reduced dose rivaroxaban (15 mg once daily) will be given to participants with a creatinine clearance 15-50 mL/min.

Interventions

Apixaban

Study participants will be randomized to twice daily oral administration of apixaban 5mg. Reduced dose apixaban (2.5 mg twice daily) will be given to participants who meet 2 of the 3 criteria: age 80 years, body weight 60 kg, and serum creatinine 1.5 mg/dL.

Intervention Type: DRUG

Rivaroxaban

Study participants will be randomized to daily oral administration of rivaroxaban 20mg. Reduced dose rivaroxaban (15 mg once daily) will be given to participants with a creatinine clearance 15-50 mL/min.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. Male or female Veteran, aged 22 years or older

2. Diagnosis of AF or AFL

3. CHADS2VASc >=3

4. Ability to take oral medication and self-reported willingness to adhere to the prespecified apixaban or rivaroxaban regimen

Exclusion Criteria

An individual who meets any of the following criteria will be excluded from participation in this study; notably use of antiplatelet agents or prior OAC use will not be an exclusion criterion:

1. Current use of oral or injectable anticoagulation, without ability to switch to the assigned study medication

2. Another indication for anticoagulation, such as pulmonary embolism

3. Contraindication to oral anticoagulation

4. Known bleeding diathesis

5. Pregnancy or lactation

6. Known allergic reactions or intolerance to apixaban or rivaroxaban

7. Estimated glomerular filtration rate (eGFR) of < 30 mL/minute

8. Mechanical heart valve

9. Moderate-severe mitral stenosis

10. History of left atrial occlusion, excision, or ligation

11. Current or planned use of ritonavir, itraconazole, or ketoconazole

12. Cardiac or thoracic surgery in the past 3 months

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

Sponsors

U.S. Food and Drug Administration (FDA)

UNKNOWN

Sponsor Role: collaborator

VA Office of Research and Development

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

William E. Boden, MD

Role: STUDY_CHAIR

VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

Cara N Pellegrini

Role: STUDY_CHAIR

San Francisco VA Medical Center, San Francisco, CA

Locations

VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

Boston, Massachusetts, United States

Countries

United States

Central Contacts

Mustabeen Ashfaq, MS

Role: CONTACT

mustabeen.ashfaq@va.gov

(857) 364-6026

Facility Contacts

Mustabeen Ashfaq, MS

Role: primary

mustabeen.ashfaq@va.gov

857-364-6026

Other Identifiers

2037

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

2037T

Identifier Type: -

Identifier Source: org_study_id