Replication of the EINSTEIN-PE Anticoagulant Trial in Healthcare Claims Data

Completed

• Conditions: Pulmonary Embolism
• Interventions: Drug: Warfarin; Drug: Rivaroxaban

• Registration Number: NCT04879407
• Lead Sponsor: Brigham and Women's Hospital

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 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 Timeline

• Study Start: 2020-10-10
• Study First Submitted: 2021-05-04
• Study First Submitted QC: 2021-05-06
• Study First Posted: 2021-05-10
• Primary Completion: 2021-06-11
• Study Completion: 2021-06-11
• Status Verified: 2023-07
• Last Update Submitted: 2023-07-25
• Last Update Posted: 2023-07-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 98947

Inclusion Criteria

• Confirmed acute symptomatic proximal PE with or without symptomatic DVT

Exclusion Criteria

• Legal lower age limitations [Day 0, Day 0]
• Thrombectomy, insertion of a caval filter, or use of a fibrinolytic agent to treat the current episode of DVT or PE [Day -14, Day 0]
• Other indications for VKA than DVT and/or PE [Day -180, Day 0]
• Creatinine clearance <30 ml/min [Day -180, Day 0]
• Significant liver disease (e.g. acute hepatitis, chronic active hepatitis, cirrhosis) or ALAT>3x ULN [Day -180, Day 0]
• Bacterial endocarditis [Day -180, Day 0]
• Life expectancy <3 months [Day -365, Day 0]
• Active bleeding or high risk for bleeding contraindicating treatment with enoxaparin or VKA [Day -180, Day 0]
• Systolic blood pressure >180 mgHg or diastolic blood pressure >110mgHg [Day -180, Day 0]
• Childbearing potential without proper contraceptive measures, pregnancy or breastfeeding [Day -180, Day 0]
• Concomitant use of strong CYP3A4 inhibitors (e.g. HIV protease inhibitors, systemic ketoconazole) or strong CYP3A4 inducers rifampin [Day -14, Day 0]

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Warfarin	Warfarin	Reference group
Rivaroxaban	Rivaroxaban	Exposure group

Primary Outcome Measures

Name	Time	Method
Relative hazard of recurrent venous thromboembolic events	Through study completion or censoring, up to 12 months	Claims-based algorithm: see attached protocol for full definition

Secondary Outcome Measures

Name	Time	Method
Relative hazard of major bleeding	Through study completion or censoring, up to 12 months	Claims-based algorithm: see attached protocol for full definition

Trial Locations

Locations (1)

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States