Clinical trial NCT04879407: Replication of the EINSTEIN-PE Anticoagulant Trial in Healthcare Claims Data
Official title: Replication of the EINSTEIN-PE Anticoagulant Trial in Healthcare Claims Data
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pulmonary Embolism
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
First posted: 2021-05-10
Enrollment: 98947
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This study will involve a new user, parallel group, propensity score-matched, retrospective cohort study design comparing rivaroxaban to warfarin users. The patients will be required to have continuous enrollment during a baseline period of 180 days before initiation of rivaroxaban or warfarin (index date). We will restrict the analyses to patients with a diagnosis of acute symptomatic proximal PE with or without symptomatic DVT.

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.

Eligibility criteria: 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 \[Day -14, Day 0\]

Primary outcomes:
measure: Relative hazard of recurrent venous thromboembolic events
timeFrame: Through study completion or censoring, up to 12 months
Secondary outcomes:
measure: Relative hazard of major bleeding
timeFrame: Through study completion or censoring, up to 12 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Shirley Wang, PhD, ScM
role: PRINCIPAL_INVESTIGATOR
References: