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

Venous Thromboembolism Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04736420
• Other study ID #: 2018P002966-DUP-EINSTEIN-DVT
• Status: Completed
• Start date: September 22, 2020
• Est. completion date: February 18, 2021

Study information

• Verified date: July 2023
• Source: Brigham and Women's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 78605
• Est. completion date: February 18, 2021
• Est. primary completion date: February 18, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Criteria:

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

Inclusion Criteria:

• Confirmed acute symptomatic proximal DVT without symptomatic PE

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

Related Conditions & MeSH terms

• Thromboembolism
• Venous Thromboembolism

Intervention

Drug:
• Rivaroxaban
Rivaroxaban dispensing claim is used as the exposure group
• Warfarin
Warfarin dispensing claim is used as the reference group

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Brigham and Women's Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Relative hazard of venous thromboembolism	Claims-based algorithm: see attached protocol for full definition	Through study completion or point of censoring, up to 12 months
Secondary	Relative hazard of a major bleeding event	Claims-based algorithm: see attached protocol for full definition	Through study completion or point of censoring, up to 12 months