Replication of the RECORD1 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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Replication of the RECORD1 Anticoagulant Trial in Healthcare Claims Data

Conditions
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Deep Vein Thrombosis, Pulmonary Embolus

Intervention / Treatment
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* Drug: Rivaroxaban
* Drug: Enoxaparin


Participation Criteria
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Eligibility Criteria
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Please see https://drive.google.com/drive/folders/1WD618wrywYjEaXzfLTcuK-VCcnb6b-gV for full code and algorithm definitions. Inclusion Criteria: At least 18 years of age Scheduled to undergo elective total hip arthroplasty Exclusion Criteria: Scheduled to undergo staged, bilateral hip arthroplasty [Day -30, Day 0] Pregnany or breastfeeding [Day -180, Day 0] Had active bleeding or high risk of bleeding [Day -180, Day 0] Had conditions preventing bilateral venography [Day -30, Day 0] Congestive heart failure [Day -180, Day 0] Pulmonary hypertension [Day -180, Day 0] Edema of legs [Day -180, Day 0] Substantial liver disease [Day -180, Day 0] Severe renal impairment (creatinine clearance <30 ml per minute) [Day -180, Day 0] Concomitant use of protease inhibitors for the treatment of HIV [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 |
| --- | --- |
| Enoxaparin<br>Reference group | Drug: Enoxaparin<br>* Any enoxaparin dispensing claim is used as the reference group<br>|
| Rivaroxaban<br>Exposure group | Drug: Rivaroxaban<br>* Any rivaroxaban dispensing claim is used as the exposure group<br>* Other names: Xarelto;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative hazard of any deep vein thrombosis, non-fatal pulmonary embolism, or death from any cause | Claims-based algorithm: relative hazard of any deep vein thrombosis, non-fatal pulmonary embolism, or death from any cause. | Through study completion or censoring, up to 36 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 36 days |