Prediction of the COBRRA AF Anticoagulant Trial in Healthcare Claims Data

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.

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Drug: Rivaroxaban; Drug: Apixaban

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 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 through 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.

• Study Type: Observational
• Enrollment (Actual): 529536

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02120
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This study will involve a new user, parallel group, propensity score-matched, retrospective cohort study design comparing rivaroxaban to apixaban users. The patients will be required to have continuous enrollment during a baseline period of 180 days before initiation of rivaroxaban or apixaban (index date). Analysis is restricted to patients with non-valvular atrial fibrillation.

Description

Inclusion Criteria:

• At least 18 years of age
• Non-valvular atrial fibrillation

Exclusion Criteria:

• Prior anticoagulant use [Day -180, Day 0]
• Stage 4 or 5 chronic kidney disease or end-stage renal disease [Day -180, Day 0]
• Dialysis or renal transplant [Day -180, Day 0]
• Recent major or clinically relevant non-major bleeding [Day -180, Day 0]
• Other indications for anticoagulation (DVT, PE, or prosthetic heart valve) [Day -180, Day 0]
• Use of an antiplatelet [Day -180, Day 0]
• Significant liver disease and coagulopathy [Day -180, Day 0]
• Use of CYP3A4 or P-gp inhibitors or inducers [Day -180, Day 0]
• Pregnancy or breastfeeding [Day -180, Day 0]
• Cancer [Day -180, Day 0]
• Bypass surgery, obesity, or the use of a weight loss or appetite suppressor [Day -180, Day 0]
• Mitral stenosis with or without insufficiency, mitral rheumatic insufficiency, and other/unspecified mitral valve disorders [Day -180, Day 0]

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Rivaroxaban; Reference group	Drug: Rivaroxaban; Any rivaroxaban dispensing claim is used as the reference group; Other Names: Xarelto
Apixaban; Exposure group	Drug: Apixaban; Any apixaban dispensing claim is used as the exposure group; Other Names: Eliquis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative hazard of major bleeding or clinically relevant non-major bleeding events	Claims-based algorithm: relative hazard of major bleeding or clinically relevant non-major bleeding events	Through study completion or censoring, up to 365 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative hazard of major bleeding	Claims-based algorithm: relative hazard of major bleeding	Through study completion or censoring, up to 365 days
Relative hazard of clinically relevant non-major bleeding	Claims-based algorithm: relative hazard of clinically relevant non-major bleeding	Through study completion or censoring, up to 365 days
Relative hazard of all-cause mortality	Claims-based algorithm: relative hazard of all-cause mortality	Through study completion or censoring, up to 365 days
Relative hazard of stroke	Claims-based algorithm: stroke	Through study completion or censoring, up to 365 days
Relative hazard of extracranial bleeding	Claims-based algorithm: relative hazard of extracranial bleeding	Through study completion or censoring, up to 365 days
Relative hazard of intracranial bleeding	Claims-based algorithm: relative hazard of intracranial bleeding	Through study completion or censoring, up to 365 days

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Investigators: Principal Investigator: Shirley Wang, PhD, ScM, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2021
• Primary Completion (Actual): June 15, 2022
• Study Completion (Actual): June 15, 2022

Study Registration Dates

• First Submitted: February 16, 2022
• First Submitted That Met QC Criteria: February 16, 2022
• First Posted (Actual): February 25, 2022

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: July 25, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban; Apixaban
• Other Study ID Numbers: 2018P002966-DUP-COBRRA-AF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No