Replication of the TRITON-TIMI Antiplatelet Trial in Healthcare Claims Data

NCT ID: NCT04237922

Last Updated: 2023-07-27

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 43864 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-09-22
• Study Completion Date: 2021-02-18

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 is 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 according to 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.

Conditions

Antiplatelet

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

Clopidogrel 75 mg

Reference group

Clopidogrel 75mg

Intervention Type: DRUG

Clopidogrel 75 mg dispensing claim is used as the reference group

Prasugrel 10 mg

Exposure group

Prasugrel 10mg

Intervention Type: DRUG

Prasugrel 10mg dispensing claim is used as the exposure group

Interventions

Prasugrel 10mg

Prasugrel 10mg dispensing claim is used as the exposure group

Intervention Type: DRUG

Clopidogrel 75mg

Clopidogrel 75 mg dispensing claim is used as the reference group

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 1. Acute coronary syndrome based on the disease diagnostic criteria with planned PCI (ACS definition; one of the following):

• 1a. Moderate to high risk Unstable angina: A history of chest discomfort or ischemic symptoms of 10 min or longer at rest, 72 h or less before randomization, with persistent or transient ST-segment deviation 1 mm or higher in one or more electrocardiogram (ECG) leads without elevation of creatine kinase-MB (CK-MB) or troponin T or I but with a TIMI risk score 321 or greater
• 1b. II. Moderate to high-risk NSTEMI. A history of chest discomfort or ischemic symptoms of 10 min or longer at rest, 72 h or less before randomization with no evidence of persistent ST-segment elevation. Subjects must also have CK-MB or troponin T or I greater than the upper limit of normal (ULN) and a TIMI risk score 3 or greater. If CK-MB or troponin is not available, total CK 2 times or greater ULN is acceptable
• 1c. III. STEMI. A history of chest discomfort or ischemic symptoms of greater than 20 minutes duration at rest, within 14 days or less randomization with one of the following ECG features:

1. ST-segment elevation 1 mm or higher in 2 or more contiguous ECG leads

2. New or presumably new left bundle branch block

3. ST-segment depression 1 mm or greater in 2 anterior precordial leads (V1 through V4) with clinical history and evidence suggestive of true posterior infarction"

• 2. Legal age (and >18 y) and competent mental condition to provide written informed consent
• 3. For women of childbearing potential only, test negative for pregnancy between ACS presentation and enrollment (based on a urine or serum pregnancy test) and agree to use a reliable method of birth control during the study

Exclusion Criteria

• 1. Cardiogenic shock at the time of randomization
• 2. Refractory ventricular arrhythmias
• 3. New York Heart Association class IV congestive heart failure

• 4. Fibrin-specific fibrinolytic therapy less than 24 h before randomization
• 5. Non-fibrin-specific fibrinolytic therapy less than 48 h before randomization
• 6. Active internal bleeding or history of bleeding diathesis
• 7. Clinical findings, in the judgment of the investigator, associated with an increased risk of bleeding
• 8. Any of the following:

1. History of hemorrhagic stroke

2. Intracranial neoplasm, arteriovenous malformation, or aneurysm

3. Ischemic stroke within 3 months prior to screening

• 9. International normalized ratio known to be greater than 1.5 at the time of screening
• 10. Platelet count of less than 100000/mm3 at the time of screening
• 11. Anemia (hemoglobin b10 g/dL) at the time of screening

• 12. One or more doses of a thienopyridine 5 d or less before PCI
• 13. Oral anticoagulation or other antiplatelet therapy that cannot be safely discontinued for the duration of the study
• 14. Daily treatment with nonsteroidal antiinflammatory drugs (NSAIDs) or cyclooxygenase-2 inhibitors (COX-2 inhibitors)

• 15. Investigative site personnel directly affiliated with the study or immediate family
• 16. Employed by Eli Lilly and Company; Ube Industries Limited, Daiichi Sankyo Co.; The TIMI Study Group; Quintiles
• 17. Treatment within the last 30 d with an investigational drug or are presently enrolled in another drug or device study
• 18. Previously completed or withdrawn from this study or any other study investigating prasugrel
• 19. Women who are known to be pregnant, have given birth within the past 90 d, or are breast-feeding
• 20. Concomitant medical illness that in the opinion of the investigator is associated with reduced survival
• 21. Known severe hepatic dysfunction
• 22. Any condition associated with poor treatment compliance including alcoholism, mental illness, or drug dependence
• 23. Intolerance of or allergy to aspirin, tilopidine, or clopidogrel
• 24. May be unable to cooperate with protocol requirements and follow-up procedures

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Shirley Vichy Wang

Associate Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Shirley Wang, PhD, ScM

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

Brigham And Women's Hospital

Boston, Massachusetts, United States

Countries

United States

References

Franklin JM, Patorno E, Desai RJ, Glynn RJ, Martin D, Quinto K, Pawar A, Bessette LG, Lee H, Garry EM, Gautam N, Schneeweiss S. Emulating Randomized Clinical Trials With Nonrandomized Real-World Evidence Studies: First Results From the RCT DUPLICATE Initiative. Circulation. 2021 Mar 9;143(10):1002-1013. doi: 10.1161/CIRCULATIONAHA.120.051718. Epub 2020 Dec 17.

Reference Type: DERIVED

PMID: 33327727 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2018P002966-DUP-TRITON-TIMI

Identifier Type: -

Identifier Source: org_study_id