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

NCT04237922 | Completed FDA Drug

• 1 other identifier: 2018P002966-DUP-TRITON-TIMI
• Study Type: observational
• Target: 43,864
• Locations: 1 country
• Sites: 1

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.

Conditions

Antiplatelet

Outcome Measures

Primary Outcomes (1)

• Relative hazard of 3-P MACE (composite outcome of Stroke, MI, and Mortality)

  Relative hazard of 3-point major adverse cardiovascular events (MACE), i.e., non-fatal myocardial infarction, non-fatal stroke, or all-cause/CV mortality- Please refer to uploaded protocol for full definition due to size limitations.

  Through study completion (a median of 276-312 days)

Secondary Outcomes (3)

• Relative hazard of Hospital admission for MI

  Through study completion (a median of 276-312 days)

• Relative hazard of Hospital admission for stroke

  Through study completion (a median of 276-312 days)

• Relative hazard of All-cause mortality/CV mortality

  Through study completion (a median of 276-312 days)

Other Outcomes (2)

• Relative hazard of Major bleeding (Control outcome)

  Through study completion (a median of 276-312 days)

• Relative hazard of Pneumonia (Control outcome)

  Through study completion (a median of 276-312 days)

Study Arms (2)

Clopidogrel 75 mg

Reference group

Drug: Clopidogrel 75mg

Prasugrel 10 mg

Exposure group

Drug: Prasugrel 10mg

Interventions

Prasugrel 10mg DRUG

Prasugrel 10mg dispensing claim is used as the exposure group

Prasugrel 10 mg

Clopidogrel 75mg DRUG

Clopidogrel 75 mg dispensing claim is used as the reference group

Clopidogrel 75 mg

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This study will involve a new user, parallel group, cohort study design comparing prasugrel 90mg to clopidogrel 75mg. The patients will be required to have continuous enrollment during the baseline period of 180 days before initiation of prasugrel 90mg or a comparator drug (cohort entry date). Follow-up for the outcome (3P-MACE), begins the day after drug initiation.

You may qualify if:

• \. Acute coronary syndrome based on the disease diagnostic criteria with planned PCI (ACS definition; one of the following):
• a. 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
• b. 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
• c. 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:
• ST-segment elevation 1 mm or higher in 2 or more contiguous ECG leads
• New or presumably new left bundle branch block
• 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"
• \. Legal age (and \>18 y) and competent mental condition to provide written informed consent
• \. 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

You may not qualify if:

• \. Cardiogenic shock at the time of randomization
• \. Refractory ventricular arrhythmias
• \. New York Heart Association class IV congestive heart failure
• \. Fibrin-specific fibrinolytic therapy less than 24 h before randomization
• \. Non-fibrin-specific fibrinolytic therapy less than 48 h before randomization
• \. Active internal bleeding or history of bleeding diathesis
• \. Clinical findings, in the judgment of the investigator, associated with an increased risk of bleeding
• \. Any of the following:
• History of hemorrhagic stroke
• Intracranial neoplasm, arteriovenous malformation, or aneurysm
• Ischemic stroke within 3 months prior to screening
• \. International normalized ratio known to be greater than 1.5 at the time of screening
• \. Platelet count of less than 100000/mm3 at the time of screening
• \. Anemia (hemoglobin b10 g/dL) at the time of screening
• \. One or more doses of a thienopyridine 5 d or less before PCI

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (1)

Brigham And Women's Hospital

Boston, Massachusetts, 02120, United States

Location

Related Publications (1)

• 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.

  PMID: 33327727 DERIVED

MeSH Terms

Interventions

Prasugrel Hydrochloride; Clopidogrel

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Ticlopidine; Thienopyridines; Pyridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Shirley Wang, PhD, ScM

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: January 17, 2020
• First Posted: January 23, 2020
• Study Start: September 22, 2019
• Primary Completion: February 18, 2021
• Study Completion: February 18, 2021
• Last Updated: July 27, 2023

Record last verified: 2023-07

Locations

US (1)