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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Enoxaparin | Reference group |
| |
| Rivaroxaban | Exposure group |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Rivaroxaban | Drug | Any rivaroxaban dispensing claim is used as the exposure group |
|
| Measure | Description | Time Frame |
|---|---|---|
| Time to first occurrence of deep-vein thrombosis, nonfatal pulmonary embolism, or death from any cause at 36 days | The primary outcome is the time from 1 day after prescription fill of the exposure or comparator to the first occurrence of any component of the composite endpoint: deep-vein thrombosis, nonfatal pulmonary embolism, or death from any cause within 36 days after elective total hip arthroplasty, comparing rivaroxaban versus enoxaparin. | From 1 day after fill until the earliest of outcome occurrence, end of data or study period, death, treatment discontinuation +10-day grace/risk window, nursing home admission, treatment augmentation, switch to other NOAC/Warfarin, assessed up to 36 days |
| Measure | Description | Time Frame |
|---|---|---|
| Time to first occurrence of major bleeding | The control outcome is the time from 1 day after prescription fill of the exposure or comparator to the first occurrence of major bleeding as a control outcome, comparing rivaroxaban versus enoxaparin. | From 1 day after fill until the earliest of outcome occurrence, end of data or study period, death, treatment discontinuation +10-day grace/risk window, nursing home admission, treatment augmentation, switch to other NOAC/Warfarin, assessed up to 36 days |
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Please see https://drive.google.com/drive/folders/1WD618wrywYjEaXzfLTcuK-VCcnb6b-gV for full code and algorithm definitions.
Inclusion Criteria:
Exclusion Criteria:
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This study will involve a new user, parallel group, propensity score-matched, retrospective cohort study design comparing rivaroxaban to enoxaparin users. The patients will be required to have continuous enrollment during a baseline period of 180 days before initiation of rivaroxaban or enoxaparin (index date). We will restrict the analyses to patients who underwent a total hip arthroplasty.
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| Name | Affiliation | Role |
|---|---|---|
| Shirley Wang, PhD, ScM | Brigham and Women's Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Brigham and Women's Hospital | Boston | Massachusetts | 02120 | United States |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol: RCT-DUPLICATE version | Jul 9, 2021 | Jun 8, 2026 | Prot_001.pdf |
| Prot | Yes | No | No | Study Protocol: BenchExCal version | May 10, 2026 | Jun 5, 2026 | Prot_002.pdf |
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| ID | Term |
|---|---|
| D020246 | Venous Thrombosis |
| D011655 | Pulmonary Embolism |
| ID | Term |
|---|---|
| D013927 | Thrombosis |
| D016769 | Embolism and Thrombosis |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D000069552 | Rivaroxaban |
| D017984 | Enoxaparin |
| ID | Term |
|---|---|
| D013876 | Thiophenes |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D009025 | Morpholines |
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| Enoxaparin | Drug | Any enoxaparin dispensing claim is used as the reference group |
|
| Time to first occurrence of fracture or fall | 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, comparing rivaroxaban versus enoxaparin. | From 1 day after fill until the earliest of outcome occurrence, end of data or study period, death, treatment discontinuation +10-day grace/risk window, nursing home admission, treatment augmentation, switch to other NOAC/Warfarin, assessed up to 36 days |
| D008171 |
| Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D004617 | Embolism |
| D010078 |
| Oxazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006495 | Heparin, Low-Molecular-Weight |
| D006493 | Heparin |
| D006025 | Glycosaminoglycans |
| D011134 | Polysaccharides |
| D002241 | Carbohydrates |