Replication of the RECORD1 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: Deep Vein Thrombosis, Pulmonary Embolus
• Intervention / Treatment: Drug: Enoxaparin; Drug: Rivaroxaban

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): 89215

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 enoxaparin users. The patients will be required to have continuous enrollment during a baseline period of 180 days before initiation of rivaroxaban or enoxaparin (index date). We will restrict the analyses to patients who underwent a total hip arthroplasty.

Description

Please see https://drive.google.com/drive/folders/1WD618wrywYjEaXzfLTcuK-VCcnb6b-gV for full code and algorithm definitions.

Inclusion Criteria:

• At least 18 years of age
• Scheduled to undergo elective total hip arthroplasty

Exclusion Criteria:

• Scheduled to undergo staged, bilateral hip arthroplasty [Day -30, Day 0]
• Pregnany or breastfeeding [Day -180, Day 0]
• Had active bleeding or high risk of bleeding [Day -180, Day 0]
• Had conditions preventing bilateral venography [Day -30, Day 0]
• Congestive heart failure [Day -180, Day 0]
• Pulmonary hypertension [Day -180, Day 0]
• Edema of legs [Day -180, Day 0]
• Substantial liver disease [Day -180, Day 0]
• Severe renal impairment (creatinine clearance <30 ml per minute) [Day -180, Day 0]
• Concomitant use of protease inhibitors for the treatment of HIV [Day -180, Day 0]

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative hazard of any deep vein thrombosis, non-fatal pulmonary embolism, or death from any cause	Claims-based algorithm: relative hazard of any deep vein thrombosis, non-fatal pulmonary embolism, or death from any cause.	Through study completion or censoring, up to 36 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 36 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): September 22, 2020
• Primary Completion (Actual): July 21, 2021
• Study Completion (Actual): July 22, 2021

Study Registration Dates

• First Submitted: September 20, 2021
• First Submitted That Met QC Criteria: October 18, 2021
• First Posted (Actual): October 19, 2021

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: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Embolism; Thrombosis; Venous Thrombosis; Pulmonary Embolism; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Fibrinolytic Agents; Fibrin Modulating Agents; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban; Enoxaparin
• Other Study ID Numbers: 2018P002966-DUP-RECORD1

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