Replication of the RELY Anticoagulant Trial in Healthcare Claims Data

NCT ID: NCT04593043

Last Updated: 2023-07-27

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 78140 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-01-01
• 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

Dabigatran

Exposure group

Dabigatran

Intervention Type: DRUG

Dabigatran dispensing claim is used as the exposure

Interventions

Warfarin

Warfarin dispensing claim is used as the reference

Intervention Type: DRUG

Dabigatran

Dabigatran dispensing claim is used as the exposure

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 1. AF documented as follows: (1a or 1b or 1c)

• 1a. There is ECG documented AF on the day of screening or randomization
• 1b. The patient has had a symptomatic episode of paroxysmal or persistent AF documented by 12-lead ECG within 6 m before randomization
• 1c. There is documentation of symptomatic or asymptomatic paroxysmal or persistent AF on 2 separate occasions, at least 1 day apart, one of which is within 6 m before randomization.
• 2. In addition to documented AF, patients must have one of the following: (2a or 2b or 2c or 2d or 2e)

• 2a. History of previous stroke, TIA, or systemic embolism
• 2b. Ejection fraction <40% documented by echocardiogram, radionuclide or contrast angiogram in the last 6 m
• 2c. Symptomatic heart failure, New York Heart Association class 2 or higher in the last 6 m
• 2d. Age ≥75 y
• 2e. Age ≥65 y and one of the following:

• Diabetes mellitus on treatment
• Documented coronary artery disease (any of: prior myocardial infarction, positive stress test, positive nuclear perfusion study, prior CABG surgery or PCI, angiogram showing ≥75% stenosis in a major coronary artery
• Hypertension requiring medical treatment
• 3. Age >18 y at entry

Exclusion Criteria

• 1. History of heart valve disorders (ie, prosthetic valve or hemodynamically relevant valve disease)
• 2. Severe, disabling stroke within the previous 6 months or Any stroke within the previous 14 days
• 3. Conditions associated with an increased risk of bleeding:

• 3a. Major surgery in the previous month
• 3c. History of intracranial, intraocular, spinal, retroperitoneal or atraumatic intra-articular bleeding
• 3d. Gastrointestinal hemorrhage within the past year
• 3e. Symptomatic or endoscopically documented gastroduodenal ulcer disease in the previous 30 days
• 3f. Hemorrhagic disorder or bleeding diathesis
• 3i. Uncontrolled hypertension (systolic blood pressure >180 mm Hg and/ or diastolic blood pressure >100 mm Hg)
• 7. Severe renal impairment (estimated creatinine clearance ≤30 mL/min)
• 8. Active infective endocarditis
• 9. Active liver disease
• 10. Women who are pregnant or of childbearing potential who refuse to use a medically acceptable form of contraception throughout the study
• 11. Anemia (hemoglobin level < 100g/L) or thrombocytopenia (platelet count <100 × 109/L)
• 14. Patients considered unreliable by the investigator or have a life expectancy less than the expected duration of the trial because of concomitant disease, or has any condition which in the opinion of the investigator, would not allow safe participation in the study (eg, drug addiction, alcohol abuse)

• 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

Shirley Wang, 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-RELY

Identifier Type: -

Identifier Source: org_study_id