Venous Thromboembolism
Conditions
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.
Interventions
DRUGRivaroxaban
Rivaroxaban dispensing claim is used as the exposure group
DRUGWarfarin
Warfarin dispensing claim is used as the reference group
Sponsors
Brigham and Women's Hospital
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to first occurrence of venous thromboembolism | From 1 day after prescription fill until outcome occurrence or censoring due to end of follow-up, death, treatment discontinuation, nursing home admission, treatment augmentation, or switch to another NOAC, assessed up to 1 year. | The primary outcome is the time from 1 day after prescription fill of the exposure or comparator to the first occurrence of venous thromboembolism up to 1 year |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to first occurrence of major bleeding | From 1 day after prescription fill until outcome occurrence or censoring due to end of follow-up, death, treatment discontinuation, nursing home admission, treatment augmentation, or switch to another NOAC, assessed up to 1 year. | The control outcome is the time from 1 day after prescription fill of the exposure or comparator to the first occurrence of a major bleeding event as a control outcome up to 1 year |
| Time to first occurrence of fracture or fall | From 1 day after prescription fill until outcome occurrence or censoring due to end of follow-up, death, treatment discontinuation, nursing home admission, treatment augmentation, or switch to another NOAC, assessed up to 1 year. | The control outcome is the time from 1 day after prescription fill of the exposure or comparator to the first occurrence of fracture or fall as a control outcome up to 1 year |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORShirley Wang, PhD, ScM
Brigham and Women's Hospital
Outcome results
None listed