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Replication of the PLATO Antiplatelet Trial in Healthcare Claims Data

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ClinicalTrials.gov Identifier: NCT04237935
Recruitment Status : Active, not recruiting
First Posted : January 23, 2020
Last Update Posted : January 23, 2020
Sponsor:
Information provided by (Responsible Party):
Jessica Franklin, Brigham and Women's Hospital

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.

Condition or disease Intervention/treatment
Antiplatelet Drug: Ticagrelor 90mg Drug: Clopidogrel 75mg

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.

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Study Type : Observational
Actual Enrollment : 27960 participants
Observational Model: Cohort
Time Perspective: Retrospective
Official Title: Replication of the PLATO Antiplatelet Trial in Healthcare Claims Data
Actual Study Start Date : September 22, 2019
Estimated Primary Completion Date : September 22, 2020
Estimated Study Completion Date : September 22, 2020

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Clopidogrel 75 mg
Reference group
Drug: Clopidogrel 75mg
Clopidogrel 75 mg dispensing claim is used as the reference group

Ticagrelor 90 mg
Exposure group
Drug: Ticagrelor 90mg
Ticagrelor 90 mg dispensing claim is used as the exposure group




Primary Outcome Measures :
  1. Relative hazard of 3-P MACE (composite outcome of Stroke, MI, and Mortality) [ Time Frame: Through study completion (a median of 163-219 days) ]
    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.


Secondary Outcome Measures :
  1. Relative hazard of Hospital admission for MI [ Time Frame: Through study completion (a median of 163-219 days) ]
    Relative hazard of Hospital admission for MI - Please refer to uploaded protocol for full definition due to size limitations.

  2. Relative hazard of Hospital admission for stroke [ Time Frame: Through study completion (a median of 163-219 days) ]
    Relative hazard of Hospital admission for stroke - Please refer to uploaded protocol for full definition due to size limitations.

  3. Relative hazard of All-cause mortality/CV mortality [ Time Frame: Through study completion (a median of 163-219 days) ]
    Relative hazard of All-cause mortality/CV mortality- Please refer to uploaded protocol for full definition due to size limitations.


Other Outcome Measures:
  1. Relative hazard of Major bleeding (Control outcome) [ Time Frame: Through study completion (a median of 163-219 days) ]
    Relative hazard of Major bleeding (Control outcome) - Please refer to uploaded protocol for full definition due to size limitations.

  2. Relative hazard of Pneumonia (Control outcome) [ Time Frame: Through study completion (a median of 163-219 days) ]
    Relative hazard of Pneumonia (Control outcome) - Please refer to uploaded protocol for full definition due to size limitations.



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
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.
Criteria

Please see: https://drive.google.com/drive/folders/1WD618wrywYjEaXzfLTcuK-VCcnb6b-gV for full code and algorithm definitions.

Market availability of ticagrelor in the U.S. started on 2011-07-20.

  • For Marketscan: 2011-07-20 to 2017-12-31 (end of data availability).
  • For Optum: 2011-07-20 to 2019-03-31 (end of data availability).

Inclusion Criteria:

  • 1-4 ALL REQUIRED

    • 1. 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
    • 2. ≥18 years of age
    • 3. 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.
    • 4. With informed consent 1-4 AND 5A OR 5B
  • 5A. ≥2 of the following:

    • 1. ST-segment changes on ECG indicating ischemia. ST-segment depression or transient elevation ≥ 1 mm in two or more 2 contiguous leads"
    • 2. Positive biomarker indicating myocardial necrosis. Troponin I or T or CK-MB greater than the upper limit of normal
    • 3. One of the following:

      1. ≥60 y of age
      2. Previous MI or CABG
      3. CAD with ≥50% stenosis in ≥2 vessels
      4. Previous ischemic stroke, TIA (hospital-based diagnosis), carotid stenosis (≥50%), or cerebral revascularization
      5. Diabetes mellitus
      6. Peripheral artery disease
      7. Chronic renal dysfunction
  • OR
  • 5B. Persistent ST-segment elevation ≥1 mm (not known to be preexisting or due to a coexisting disorder) in ≥2 contiguous leads or new LBBB plus primary PCI planned.

Exclusion Criteria:

  • Drug related

    • 1. 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)"
    • 2. Oral anticoagulation therapy that cannot be stopped
    • 3. Fibrinolytic therapy planned or within the previous 24 h
    • 4. 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

    • 1. Index event is an acute complication of PCI
    • 2. PCI after index event and before first study dose
  • Medical

    • 1. Increased risk of bradycardiac events
    • 2. Dialysis required
    • 3. Known clinically important thrombocytopenia
    • 4. Known clinically important anemia
    • 5. 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

    • 1. Participant in another investigational drug or device study within 30 days
    • 2. Pregnancy or lactation
    • 3. Any condition that increases the risk for noncompliance or being lost to follow-up
    • 4. Involvement in the planning or conduct of the study
    • 5. Previous enrollment or randomization in this study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04237935


Locations
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United States, Massachusetts
Brigham And Women's Hospital
Boston, Massachusetts, United States, 02120
Sponsors and Collaborators
Brigham and Women's Hospital
Investigators
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Principal Investigator: Jessica Franklin, PhD Brigham and Women's Hospital
  Study Documents (Full-Text)

Documents provided by Jessica Franklin, Brigham and Women's Hospital:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Jessica Franklin, Assistant Professor of Medicine, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT04237935    
Other Study ID Numbers: DUPLICATE-PLATO
First Posted: January 23, 2020    Key Record Dates
Last Update Posted: January 23, 2020
Last Verified: January 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Clopidogrel
Ticagrelor
Platelet Aggregation Inhibitors
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs