Emulation of the RECORD3 Trial Using 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: Active, not recruiting
• 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): 149248

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: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients aged 18 years or older undergoing elective total knee arthroplasty. In addition, patients will be excluded with fractures or falls prior to the follow-up time window (30 days) when studying the negative outcome, respectively.

Description

Inclusion Criteria:

• At least 18 years of age
• Scheduled to undergo elective total knee replacement

Exclusion Criteria:

• Pregnany or breastfeeding [Day -365, Day 0]
• Had active bleeding or high risk of bleeding [Day -183, Day 0]
• Had contraindications for prophylaxis with enoxaparin [Day -183, Day 0]
• Drug or alcohol abuse [Day -183, Day 0]
• Concomitant use of protease inhibitors for the treatment of HIV [Day -183, Day 0]
• Had planned intermittent pneumatic compression [Day -183, Day 0]
• Had a requirement for anticoagulant therapy that could not be stopped [Day -183, Day 0]
• Substantial liver disease [Day -180, Day 0]
• Severe renal impairment (creatinine clearance <30 ml per minute) [Day -180, Day 0]
• Concurrent use of both drugs [Day 0, 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; Initiation of rivaroxaban described in electronic health records is used as the exposure.; Other Names: Xarelto
Enoxaparin; Reference group	Drug: Enoxaparin; Initiation of enoxaparin described in electronic health records is used as the reference.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite of deep-vein thrombosis, nonfatal pulmonary embolism, or death from any cause at 17 days.	To compare the comparative effect of rivaroxaban vs enoxaparin on the risk of deep vein thrombosis, nonfatal pulmonary embolism or death from any cause in patients who underwent elective total knee arthroplasty.	One day after prescription fill of exposure or comparator until outcome, end of data, end of study period, death, discontinuation (7 day grace and risk-window), nursing home admission, augmentation/additional exposure or switch to other NOAC or warfarin

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fractures or falls	To evaluate the comparative effect of rivaroxaban vs enoxaparin on the control outcome fractures or falls.	One day after prescription fill of exposure or comparator until outcome, end of data, end of study period, death, discontinuation (7 day grace and risk-window), nursing home admission, augmentation/additional exposure or switch to other NOAC or warfarin

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): October 13, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: May 14, 2026
• First Submitted That Met QC Criteria: May 14, 2026
• First Posted (Actual): May 20, 2026

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 14, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Embolism; Thrombosis; Pulmonary Embolism; Venous Thrombosis; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbohydrates; Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Morpholines; Oxazines; Thiophenes; Rivaroxaban; Enoxaparin
• Other Study ID Numbers: 2018P002966-RECORD3

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