Clinical trial NCT04736420: Replication of the EINSTEIN-DVT Anticoagulant Trial in Healthcare Claims Data
Official title: Replication of the EINSTEIN-DVT Anticoagulant Trial in Healthcare Claims Data
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Venous Thromboembolism
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
First posted: 2021-02-03
Enrollment: 78605
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 proximal DVT without symptomatic PE.

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 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

Primary outcomes:
measure: Relative hazard of venous thromboembolism
timeFrame: Through study completion or point of censoring, up to 12 months
Secondary outcomes:
measure: Relative hazard of a major bleeding event
timeFrame: Through study completion or point of 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: