Prediction of the COBRRA VTE Anticoagulant Trial in Healthcare Claims Data

Study Overview
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Brief Summary
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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
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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.

Official Title
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Prediction of the COBRRA VTE Anticoagulant Trial in Healthcare Claims Data

Conditions
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Venous Thromboembolism, Pulmonary Embolism, DVT

Intervention / Treatment
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* Drug: Rivaroxaban
* Drug: Apixaban


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Hospitalization for PE or Proximal DVT [Day -14, Day 0] At least 18 years of age Exclusion Criteria: Prior use of a DOAC or warfarin [Day -180, Day 0] Stage 4 or 5 chronic kidney disease or end-stage renal disease [Day -180, Day 0] Dialysis or renal transplant [Day -180, Day 0] Recent major or clinically relevant non-major bleeding [Day -180, Day 0] Cancer [Day -180, Day 0] Bypass surgery, obesity, or the use of a weight loss or appetite suppressor [Day -180, Day 0] Significant liver disease and coagulopathy [Day -180, Day 0] Use of CYP3A4 or P-gp inhibitors or inducers [Day -180, Day 0] Other indications for anticoagulation (atrial fibrillation or prosthetic heart valve) [Day -180, Day 0] Pregnancy or breastfeeding [Day -180, Day 0] Use of an antiplatelet [Day -180, Day 0]

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Rivaroxaban<br>Reference group | Drug: Rivaroxaban<br>* Any rivaroxaban dispensing claim is used as the reference group<br>* Other names: Xarelto;|
| Apixaban<br>Exposure group | Drug: Apixaban<br>* Any apixaban dispensing claim is used as the exposure group<br>* Other names: Eliquis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative hazard of major bleeding or clinically relevant non-major bleeding events | Claims-based algorithm: relative hazard of major bleeding or clinically relevant non-major bleeding events | Through study completion or censoring, up to 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative hazard of major bleeding | Claims-based algorithm: relative hazard of major bleeding | Through study completion or censoring, up to 90 days | 
| Relative hazard of clinically relevant non-major bleeding | Claims-based algorithm: relative hazard of clinically relevant non-major bleeding | Through study completion or censoring, up to 90 days | 
| Relative hazard of all-cause mortality | Claims-based algorithm: relative hazard of all-cause mortality | Through study completion, up to 90 days | 
| Relative hazard of recurrent VTE | Claims-based algorithm: relative hazard of recurrent VTE | Through study completion, up to 90 days | 
| Relative hazard of extracranial bleeding | Claims-based algorithm: relative hazard of extracranial bleeding | Through study completion, up to 90 days | 
| Relative hazard of intracranial bleeding | Claims-based algorithm: relative hazard of intracranial bleeding | Through study completion, up to 90 days |