Replication of the ISAR-REACT 5 Antiplatelet 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 ISAR-REACT 5 Antiplatelet Trial in Healthcare Claims Data

Conditions
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Acute Coronary Syndrome

Intervention / Treatment
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* Drug: Ticagrelor 90mg
* Drug: Prasugrel 10mg


Participation Criteria
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Eligibility Criteria
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Criteria: Please see https://drive.google.com/drive/folders/1WD618wrywYjEaXzfLTcuK-VCcnb6b-gV for full code and algorithm definitions. Inclusion Criteria: Hospitalization for unstable angina or acute MI AND age >= 18 years Days [ACS admission] STEMI OR NSTEMI/unstable angina (during admission) + 1 of the following >= 60 years old Days [ACS] >= 3 risk factors for coronary artery disease Diabetes mellitus Chronic renal disease Carotid stenosis >= 50% or cerebral revascularization Peripheral artery disease Days [-365, ACS] Aspirin use Angina Days [-7, ACS] Prior MI or CABG any time prior Exclusion Criteria: Acute complication PCI Days [-30, ACS admission] History of any stroke or TIA Days [all available data, 0] Intracranial neoplasm, intracranial AVM, intracranial neoplasm Days [-180, 0] Active bleeding Days [-180, 0] Platelet count < 100.000/uL Days [-180, 0] Anemia (hemoglobin < 10 g/dL) Days [-180, 0] Chronic renal insufficiency requiring dialysis Days [-180, 0] Moderate to severe hepatic dysfunction Days [-180, 0] Increased risk of bradycardia events Days [-180, 0] Life expectancy, 1 year Days [-180, 0] Pregnancy Days [-180, 0] Concomitant therapy CYP3A inhibitors, CYP3A substrates, or strong CYP3A inducers Days [-14, 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 |
| --- | --- |
| Prasugrel<br>Reference group | Drug: Prasugrel 10mg<br>* Any prasugrel dispensing claim is used as the reference group<br>|
| Ticagrelor<br>Exposure group | Drug: Ticagrelor 90mg<br>* Any ticagrelor dispensing claim is used as the exposure group<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative hazard of composite of death, myocardial infarction, or stroke at 1 year after randomization | Claims-based algorithm: Relative hazard of composite of death, myocardial infarction, or stroke at 1 year after randomization | Through study completion or censoring, up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative hazard of hospital admission for MI, hospital admission for stroke, or death | Claims-based algorithm: Relative hazard of hospital admission for MI, hospital admission for stroke, or death | Through study completion or censoring, up to 12 months | 
| Relative hazard of major bleeding | Claims-based algorithm: relative hazard of major bleeding | Through study completion or censoring, up to 12 months |