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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 |
|---|---|---|---|
| Rivaroxaban | Reference group |
| |
| Apixaban | Exposure group |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Rivaroxaban | Drug | Any rivaroxaban dispensing claim is used as the reference group |
|
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Major Bleeding or Clinically Relevant Non-major Bleeding Events | Claims-based algorithm: incidence of major bleeding or clinically relevant non-major bleeding events | Through study completion or censoring, up to 365 days |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Major Bleeding | Claims-based algorithm: Incidence of major bleeding | Through study completion or censoring, up to 365 days |
| Incidence of Clinically Relevant Non-major Bleeding | Claims-based algorithm: Incidence of clinically relevant non-major bleeding |
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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 apixaban users. The patients will be required to have continuous enrollment during a baseline period of 180 days before initiation of rivaroxaban or apixaban (index date). Analysis is restricted to patients with non-valvular atrial fibrillation.
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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 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 42389777 | Derived | Mahesri M, Schneeweiss S, Lin KJ, Zabotka L, Concato J, Bradley MC, Wang SV. Bleeding Risk With Apixaban Versus Rivaroxaban: A Reference Trial Emulation Predicting the Results of COBRRA-VTE and COBRRA-AF Using US Health Care Claims. Circ Popul Health Outcomes. 2026 Jul 2:e012892. doi: 10.1161/CIRCOUTCOMES.125.012892. Online ahead of print. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Rivaroxaban | Reference group Rivaroxaban: Any rivaroxaban dispensing claim is used as the reference group |
| FG001 | Apixaban | Exposure group Apixaban: Any apixaban dispensing claim is used as the exposure group |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Rivaroxaban | Reference group Rivaroxaban: Any rivaroxaban dispensing claim is used as the reference group |
| BG001 | Apixaban | Exposure group Apixaban: Any apixaban dispensing claim is used as the exposure group |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Incidence of Major Bleeding or Clinically Relevant Non-major Bleeding Events | Claims-based algorithm: incidence of major bleeding or clinically relevant non-major bleeding events | Propensity score matched population across 3 databases | Posted | Number | 95% Confidence Interval | No. of new events per 100 person-years | Through study completion or censoring, up to 365 days |
|
All-Cause Mortality was monitored/assessed from enrollment to completion of study, up to 365 days
Only All-Cause Mortality was monitored/assessed. Serious and Other (Not Including Serious) Adverse Events were not monitored/assessed
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Rivaroxaban | Reference group Rivaroxaban: Any rivaroxaban dispensing claim is used as the reference group |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Shirley Wang | Brigham and Women's Hospital | 617-525-8376 | swang1@bwh.harvard.edu |
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 7, 2022 | Jan 28, 2025 | Prot_002.pdf |
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| ID | Term |
|---|---|
| D001281 | Atrial Fibrillation |
| ID | Term |
|---|---|
| D001145 | Arrhythmias, Cardiac |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D010335 | Pathologic Processes |
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| ID | Term |
|---|---|
| D000069552 | Rivaroxaban |
| C522181 | apixaban |
| ID | Term |
|---|---|
| D013876 | Thiophenes |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D009025 | Morpholines |
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| Apixaban | Drug | Any apixaban dispensing claim is used as the exposure group |
|
|
| Through study completion or censoring, up to 365 days |
| Incidence of All-cause Mortality | Claims-based algorithm: Incidence of all-cause mortality | Through study completion or censoring, up to 365 days |
| Incidence of Stroke | Claims-based algorithm: Incidence of stroke | Through study completion or censoring, up to 365 days |
| Incidence of Extracranial Bleeding | Claims-based algorithm: Incidence of extracranial bleeding (any position) | Through study completion or censoring, up to 365 days |
| Incidence of Intracranial Bleeding | Claims-based algorithm: Incidence of intracranial bleeding (any position) | Through study completion or censoring, up to 365 days |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
|
| Secondary | Incidence of Major Bleeding | Claims-based algorithm: Incidence of major bleeding | Propensity score matched population across 3 databases | Posted | Number | 95% Confidence Interval | No. of new events per 100 person-years | Through study completion or censoring, up to 365 days |
|
|
|
| Secondary | Incidence of Clinically Relevant Non-major Bleeding | Claims-based algorithm: Incidence of clinically relevant non-major bleeding | Propensity score matched population across 3 databases | Posted | Number | 95% Confidence Interval | No. of new events per 100 person-years | Through study completion or censoring, up to 365 days |
|
|
|
| Secondary | Incidence of All-cause Mortality | Claims-based algorithm: Incidence of all-cause mortality | Propensity score matched population across 3 databases | Posted | Number | 95% Confidence Interval | No. of new events per 100 person-years | Through study completion or censoring, up to 365 days |
|
|
|
| Secondary | Incidence of Stroke | Claims-based algorithm: Incidence of stroke | Propensity score matched population across 3 databases | Posted | Number | 95% Confidence Interval | No. of new events per 100 person-years | Through study completion or censoring, up to 365 days |
|
|
|
| Secondary | Incidence of Extracranial Bleeding | Claims-based algorithm: Incidence of extracranial bleeding (any position) | Propensity score matched population across 3 databases | Posted | Number | 95% Confidence Interval | No. of new events per 100 person-years | Through study completion or censoring, up to 365 days |
|
|
|
| Secondary | Incidence of Intracranial Bleeding | Claims-based algorithm: Incidence of intracranial bleeding (any position) | Propensity score matched. population across 3 databases | Posted | Number | 95% Confidence Interval | No. of new events per 100 person-years | Through study completion or censoring, up to 365 days |
|
|
|
| 1,958 |
| 176,990 |
| 0 |
| 0 |
| 0 |
| 0 |
| EG001 | Apixaban | Exposure group Apixaban: Any apixaban dispensing claim is used as the exposure group | 1,840 | 176,990 | 0 | 0 | 0 | 0 |
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| D013568 |
| Pathological Conditions, Signs and Symptoms |
| D010078 |
| Oxazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |