Clinical trial NCT05086081: Replication of the ISAR-REACT 5 Antiplatelet Trial in Healthcare Claims Data
Official title: Replication of the ISAR-REACT 5 Antiplatelet Trial in Healthcare Claims Data
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Acute Coronary Syndrome
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
First posted: 2021-10-20
Enrollment: 28389
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: This study will involve a new user, parallel group, retrospective cohort study design comparing ticagrelor 90 mg twice daily to prasugrel 10 mg daily. The patients will be required to have continuous enrollment during the baseline period of 180 days before initiation of ticagrelor or prasugrel (index date). We will restrict the analyses to patients with an acute coronary syndrome, with or without ST-segment elevation, who were scheduled to undergo coronary angiography.

Brief summary: 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: 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.

Eligibility criteria: 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 \[-14, 0\]

Primary outcomes:
measure: Relative hazard of composite of death, myocardial infarction, or stroke at 1 year after randomization
timeFrame: Through study completion or censoring, up to 12 months
Secondary outcomes:
measure: Relative hazard of hospital admission for MI, hospital admission for stroke, or death
timeFrame: Through study completion or censoring, up to 12 months
measure: Relative hazard of major bleeding
timeFrame: Through study completion or censoring, up to 12 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Shirley Wang, PhD
role: PRINCIPAL_INVESTIGATOR
References: