Replication of the ARISTOTLE Anticoagulant Trial in Healthcare Claims Data

NCT ID: NCT04593030

Last Updated: 2023-07-27

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 220518 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-09-01
• Study Completion Date: 2021-02-18

Brief Summary

Investigators are building an empirical evidence base for real world data through large-scale replication of randomized controlled trials. The investigators' goal is to understand for what types of clinical questions real world data analyses can be conducted with confidence and how to implement such studies.

Detailed Description

This is a non-randomized, non-interventional study that is part of the RCT DUPLICATE initiative (www.rctduplicate.org) of the Brigham and Women's Hospital, Harvard Medical School. It is intended to replicate, as closely as is possible in healthcare insurance claims data, the trial listed below/above. Although many features of the trial cannot be directly replicated in healthcare claims, key design features, including outcomes, exposures, and inclusion/exclusion criteria, were selected to proxy those features from the trial. Randomization is also not replicable in healthcare claims data but was proxied through a statistical balancing of measured covariates according to standard practice. Investigators assume that the RCT provides the reference standard treatment effect estimate and that failure to replicate RCT findings is indicative of the inadequacy of the healthcare claims data for replication for a range of possible reasons and does not provide information on the validity of the original RCT finding.

Conditions

Atrial Fibrillation

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

Warfarin

Reference group

Warfarin

Intervention Type: DRUG

Warfarin dispensing claim is used as the reference

Apixaban

Exposure group

Apixaban

Intervention Type: DRUG

Apixaban dispensing claim is used as the exposure

Interventions

Warfarin

Warfarin dispensing claim is used as the reference

Intervention Type: DRUG

Apixaban

Apixaban dispensing claim is used as the exposure

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 1. Age ≥ 18 years
• 2. Atrial fibrillation - either of the following:

• 2a. In atrial fibrillation or atrial flutter not due to a reversible cause and documented by ECG at the time of enrollment
• 2b. If not in atrial fibrillation/flutter at the time of enrollment, must have atrial fibrillation/flutter documented on two separate occasions, not due to a reversible cause at least 2 weeks apart in the 12 months prior to enrollment. Atrial fibrillation/flutter may be documented by ECG, or as an episode lasting at least one minute on a rhythm strip, Holter recording, or intracardiac electrogram (from an implanted pacemaker or defibrillator)
• 3. One or more of the following risk factor(s) for stroke:

• 3a. Age 75 years or older
• 3b. Prior stroke, TIA, or systemic embolus
• 3c. Either symptomatic congestive heart failure within 3 months or left ventricular dysfunction with an LV ejection fraction (LVEF) ≤ 40% by echocardiography, radionuclide study or contrast angiography
• 3d. Diabetes mellitus
• 3e. Hypertension requiring pharmacological treatment

Exclusion Criteria

• 2. Clinically significant (moderate or severe) mitral stenosis
• 3. Increased bleeding risk that is believed to be a contraindication to oral anticoagulation (e.g. previous intracranial hemorrhage)
• 4. Conditions other than atrial fibrillation that require chronic anticoagulation (e.g. prosthetic mechanical heart valve)
• 5. Persistent, uncontrolled hypertension (systolic BP > 180 mm Hg, or diastolic BP > 100 mm Hg)
• 6. Active infective endocarditis
• 11. Simultaneous treatment with both aspirin and a thienopyridine (e.g., clopidogrel, ticlopidine)
• 12. Severe comorbid condition with life expectancy of ≤ 1 year
• 13. Active alcohol or drug abuse, or psychosocial reasons that make study participation impractical
• 14. Recent ischemic stroke (within 7 days)
• 15. Severe renal insufficiency (serum creatinine > 2.5 mg/dL or a calculated creatinine clearance < 25 mL/min, See Section 6.3.2.2)
• 17. Platelet count ≤ 100,000/ mm3
• 18. Hemoglobin < 9 g/dL
• 19. Women of child bearing potential (WOCBP) unwilling or unable to use an acceptable method to avoid pregnancy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Shirley Vichy Wang

Associate Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jessica Franklin, PhD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

Brigham And Women's Hospital

Boston, Massachusetts, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2018P002966-DUP-ARISTOTLE

Identifier Type: -

Identifier Source: org_study_id