Comparing the Safety and Efficacy of Apixaban and Rivaroxaban

NCT06953726 | Not Yet Recruiting Phase 4 DMC FDA Drug

• 2 other identifiers: 2037T2037
• Study Type: interventional
• Target: 10,000
• Locations: 1 country
• Sites: 1

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") or atrial flutter. Most participants will be age 65 or older, and should already be taking apixaban or rivaroxaban.
• The investigators 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.

Conditions

Atrial Fibrillation

Keywords

Atrial Fibrillation; Ischemic Stroke; Bleeding; Major bleeding

Outcome Measures

Primary Outcomes (4)

• Onset of ISTH Major Bleeding Event

  Hospitalization for first ISTH-defined major bleeding, as determined by ICD-10 codes associated with hospitalization. This is the primary safety outcome.

  3 years

• Time to First Stroke

  Hospitalization for first stroke, as determined by ICD-10 codes associated with hospitalization. The primary efficacy outcome is time to first event of stroke or systemic embolism, or death of any cause, in days.

  3 years

• Time to First Systemic Embolism

  Hospitalization for first systemic embolism, as determined by ICD-10 codes associated with hospitalization. The primary efficacy outcome is time to first event of stroke or systemic embolism, or death of any cause, in days.

  3 years

• Time to All-Cause Mortality

  Time to all-cause mortality, as determined by VA data on vital status. The primary efficacy outcome is time to first event of stroke or systemic embolism, or death of any cause, in days.

  3 years

Secondary Outcomes (5)

• Time to First Stroke, Systemic Embolism, or All-Cause Mortality

  3 years

• Time to First Stroke

  3 years

• Time to First Hospitalization for Heart Failure, Myocardial Infarction, or Acute Coronary Syndrome

  3 years

• Time to First systemic embolism

  3 years

• All-Cause Mortality

  3 years

Study Arms (2)

Apixaban Arm

ACTIVE COMPARATOR

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 or older, body weight of 60 kg or lower, serum creatinine of 1.5 mg/dL or higher

Drug: Apixaban

Rivaroxaban Arm

ACTIVE COMPARATOR

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

Drug: Rivaroxaban

Interventions

Apixaban 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.

Apixaban Arm

Rivaroxaban 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.

Rivaroxaban Arm

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• Male or female Veteran, aged 22 years or older
• Diagnosis of atrial fibrillation (AF) or atrial flutter (AFL) and currently taking either apixaban or rivaroxaban.
• CHA2DS2-Vasc of 3 or more
• Ability to take oral medication and self-reported willingness to adhere to the prespecified apixaban or rivaroxaban regimen

You may not qualify if:

• Current use of oral or injectable anticoagulation, without ability to switch to the assigned study medication
• Another indication for anticoagulation, such as pulmonary embolism
• Contraindication to oral anticoagulation
• Known bleeding diathesis
• Documented current pregnancy or lactation in the EHR or self-reported current pregnancy or lactation
• Known allergic reactions or intolerance to apixaban or rivaroxaban
• Most recent estimated glomerular filtration rate (eGFR) is \< 30 mL/minute/1.73m2. An eGFR result must have been obtained within 18 months before randomization.
• Known mechanical heart valve
• Known moderate-severe mitral stenosis
• Known history of left atrial occlusion, excision, or ligation
• Current or planned use of systemic ritonavir, itraconazole, or ketoconazole (topical use of ketoconazole only is allowed)
• Cardiac or thoracic surgery in the past 3 months

Sponsors & Collaborators

• VA Office of Research and Development: lead
• U.S. Food and Drug Administration (FDA): collaborator

Study Sites (1)

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

Boston, Massachusetts, 02130-4817, United States

Location

MeSH Terms

Conditions

Atrial Fibrillation; Ischemic Stroke; Hemorrhage

Interventions

apixaban; Rivaroxaban

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• William E. Boden, MD

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

  STUDY CHAIR

• Cara N Pellegrini

  San Francisco VA Medical Center, San Francisco, CA

  STUDY CHAIR

Central Study Contacts

Mustabeen Ashfaq, MS

CONTACT

(857) 364-6026; mustabeen.ashfaq@va.gov

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Drug assignment will be unblinded and distributed through VA's usual mechanism for filling medications (i.e., local pharmacy or Consolidated Mail Outpatient Pharmacy \[CMOP\]). Randomization: Allocation occurs via a centralized online tool (IWRS). Each site uses permuted-block randomization with random block sizes, pre-programmed before study start; no stratification is applied at randomization.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: Apixaban arm: 5 mg orally twice daily; 2.5 mg twice daily if the participant meets 2 or more of 3 criteria: age 80 years or older, body weight of 60 kg or lower, serum creatinine of 1.5 mg/dL or higher (per product labeling and protocol). Rivaroxaban arm: 20 mg orally once daily if creatinine clearance of 50 mL/min or more; 15 mg once daily if creatinine clearance 15-50 mL/min. (Note: eGFR \<30 mL/min/1.73 m² is an exclusion criterion in the protocol.) Participants are already taking apixaban or rivaroxaban at enrollment (AF or AFL; CHA2DS2-Vasc of 3 or more), and must be willing to switch if randomized to the other DOAC.

Study Record Dates

• First Submitted: April 23, 2025
• First Posted: May 1, 2025
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): October 4, 2032
• Study Completion (Estimated): October 3, 2033
• Last Updated: April 9, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)