Replication of the PLATO Antiplatelet Trial in Healthcare Claims Data

NCT04237935 | Completed FDA Drug

• 1 other identifier: 2018P002966-DUP-PLATO
• Study Type: observational
• Target: 27,960
• 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 163-219 days)

Secondary Outcomes (3)

• Relative hazard of Hospital admission for MI

  Through study completion (a median of 163-219 days)

• Relative hazard of Hospital admission for stroke

  Through study completion (a median of 163-219 days)

• Relative hazard of All-cause mortality/CV mortality

  Through study completion (a median of 163-219 days)

Other Outcomes (2)

• Relative hazard of Major bleeding (Control outcome)

  Through study completion (a median of 163-219 days)

• Relative hazard of Pneumonia (Control outcome)

  Through study completion (a median of 163-219 days)

Study Arms (2)

Clopidogrel 75 mg

Reference group

Drug: Clopidogrel 75mg

Ticagrelor 90 mg

Exposure group

Drug: Ticagrelor 90mg

Interventions

Ticagrelor 90mg DRUG

Ticagrelor 90 mg dispensing claim is used as the exposure group

Ticagrelor 90 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
• 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 ticagrelor 90mg twice daily to clopidogrel 75mg daily. The patients will be required to have continuous enrollment during the baseline period of 180 days before initiation of ticagrelor 90mg or the comparator drug (cohort entry date). Follow-up for the outcome (3P-MACE), begins the day after drug initiation.

You may qualify if:

• ALL REQUIRED
• \. Hospitalized for potential ST-segment elevation or non-ST-segment elevation ACS, with onset during the previous 24 hours, documented by cardiac ischemic symptoms due to atherosclerosis of ≥10 minutes' duration at rest
• \. ≥18 years of age
• \. Not pregnant. Urinary and/or blood pregnancy tests are to be performed in women of child-bearing potential and repeated at least every 6 months. Women of child-bearing potential must be using ≥2 forms of reliable contraception, including one barrier method.
• \. With informed consent 1-4 AND 5A OR 5B
• A. ≥2 of the following:
• \. ST-segment changes on ECG indicating ischemia. ST-segment depression or transient elevation ≥ 1 mm in two or more 2 contiguous leads"
• \. Positive biomarker indicating myocardial necrosis. Troponin I or T or CK-MB greater than the upper limit of normal
• \. One of the following:
• ≥60 y of age
• Previous MI or CABG
• CAD with ≥50% stenosis in ≥2 vessels
• Previous ischemic stroke, TIA (hospital-based diagnosis), carotid stenosis (≥50%), or cerebral revascularization
• Diabetes mellitus
• Peripheral artery disease

You may not qualify if:

• Drug related
• \. Contraindication to clopidogrel or other reason that study drug should not be administered (eg, hypersensitivity, moderate or severe liver disease, active bleeding or bleeding history, major surgery within 30 days)"
• \. Oral anticoagulation therapy that cannot be stopped
• \. Fibrinolytic therapy planned or within the previous 24 h
• \. Concomitant oral or IV therapy with strong CYP3A inhibitors (ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, grapefruit juice N1 L/d), CYP3A substrates with narrow therapeutic indices (cyclosporine, quinidine), or strong CYP3A inducers (rifampin/rifampicin, phenytoin, carbamazepine)
• Treatment related
• \. Index event is an acute complication of PCI
• \. PCI after index event and before first study dose
• Medical
• \. Increased risk of bradycardiac events
• \. Dialysis required
• \. Known clinically important thrombocytopenia
• \. Known clinically important anemia
• \. Any other condition that may put the patient at risk or influence study results in the investigators' opinion (eg, cardiogenic shock, severe hemodynamic instability, active cancer)
• General

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

Ticagrelor; Clopidogrel

Intervention Hierarchy (Ancestors)

Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-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)