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

Completed

• Conditions: Venous Thromboembolism
• Interventions: Drug: Rivaroxaban; Drug: Warfarin

• Registration Number: NCT04736420
• 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: 2020-09-22
• Study First Submitted: 2021-01-25
• Study First Submitted QC: 2021-01-29
• Study First Posted: 2021-02-03
• Primary Completion: 2021-02-18
• Study Completion: 2021-02-18
• Status Verified: 2023-07
• Last Update Submitted: 2023-07-25
• Last Update Posted: 2023-07-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 78605

Inclusion Criteria

• Confirmed acute symptomatic proximal DVT without symptomatic PE

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Exclusion Criteria

• Age ≤ 18

• Thrombectomy, insertion of a caval filter, or use of a fibrinolytic agent to treat the current episode of DVT or PE two weeks prior to and including day of enrollment

• Other indications for VKA than DVT and/or PE six months prior to and including day of enrollment

• Any of the following six months prior to and including day of enrollment:

  • Creatine clearance < 30 ml/min
  • Significant liver disease (e.g. acute hepatitis, chronic active hepatitis, cirrhosis) or ALAT>3 ULN
  • Bacterial endocarditis
  • Active bleeding or high risk for bleeding contraindicating treatment with enoxaparin or VKA
  • Systolic blood pressure > 180 mgHg or diastolic blood pressure > 110 mgHg
  • Childbearing potential without proper contraceptive measures, pregnancy, or breastfeeding

• Life expectancy < 3 months in the last year prior to and including day of enrollment

• Concomitant use of strong CYP3A4 inhibitors (e.g. HIV protease inhibitors, systemic ketoconazole) or strong CYP3A4 inducers two weeks prior to and including day of enrollment

• Symptomatic pulmonary embolism two weeks prior to and including day of enrollment

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Rivaroxaban	Rivaroxaban	Exposure group
Warfarin	Warfarin	Reference group

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Relative hazard of a major bleeding event	Through study completion or point of 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