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

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.

Study Overview

• Status: Completed
• Conditions: Acute Coronary Syndrome
• Intervention / Treatment: Drug: Prasugrel 10mg; Drug: Ticagrelor 90mg

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.

• Study Type: Observational
• Enrollment (Actual): 28389

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02120
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• 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.

Description

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]

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Prasugrel; Reference group	Drug: Prasugrel 10mg; Any prasugrel dispensing claim is used as the reference group
Ticagrelor; Exposure group	Drug: Ticagrelor 90mg; Any ticagrelor dispensing claim is used as the exposure group

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Investigators: Principal Investigator: Shirley Wang, PhD, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2020
• Primary Completion (Actual): September 10, 2021
• Study Completion (Actual): September 10, 2021

Study Registration Dates

• First Submitted: September 20, 2021
• First Submitted That Met QC Criteria: October 18, 2021
• First Posted (Actual): October 20, 2021

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: July 25, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Acute Coronary Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Ticagrelor; Prasugrel Hydrochloride
• Other Study ID Numbers: 2018P002966-DUP-ISAR-REACT5

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No