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

Pulmonary Embolism Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04879407
• Other study ID #: 2018P002966-DUP-EINSTEIN-PE
• Status: Completed
• Start date: October 10, 2020
• Est. completion date: June 11, 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: 98947
• Est. completion date: June 11, 2021
• Est. primary completion date: June 11, 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 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]

Related Conditions & MeSH terms

• Embolism
• Pulmonary Embolism

Intervention

Drug:
• Rivaroxaban
Any rivaroxaban dispensing claim is used as the exposure group
• Warfarin
Any 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 recurrent venous thromboembolic events	Claims-based algorithm: see attached protocol for full definition	Through study completion or censoring, up to 12 months
Secondary	Relative hazard of major bleeding	Claims-based algorithm: see attached protocol for full definition	Through study completion or censoring, up to 12 months