Rationale and design of a prospective substudy of clinical endpoint adjudication processes within an investigator-reported randomised controlled trial in patients with coronary artery disease: the GLOBAL LEADERS Adjudication Sub-StudY (GLASSY)

Sergio Leonardi, Anna Franzone, Raffaele Piccolo, Eugene McFadden, Pascal Vranckx, Patrick Serruys, Edouard Benit, Christoph Liebetrau, Luc Janssens, Maurizio Ferrario, Aleksander Zurakowski, Robert-Jan van Geuns, Marcello Dominici, Kurt Huber, Ton Slagboom, Paweł Buszman, Leonardo Bolognese, Carlo Tumscitz, Krzysztof Bryniarski, Adel Aminian, Mathias Vrolix, Ivo Petrov, Scot Garg, Christoph Naber, Janusz Prokopczuk, Christian Hamm, Gabriel Steg, Dik Heg, Peter Juni, Stephan Windecker, Marco Valgimigli, Sergio Leonardi, Anna Franzone, Raffaele Piccolo, Eugene McFadden, Pascal Vranckx, Patrick Serruys, Edouard Benit, Christoph Liebetrau, Luc Janssens, Maurizio Ferrario, Aleksander Zurakowski, Robert-Jan van Geuns, Marcello Dominici, Kurt Huber, Ton Slagboom, Paweł Buszman, Leonardo Bolognese, Carlo Tumscitz, Krzysztof Bryniarski, Adel Aminian, Mathias Vrolix, Ivo Petrov, Scot Garg, Christoph Naber, Janusz Prokopczuk, Christian Hamm, Gabriel Steg, Dik Heg, Peter Juni, Stephan Windecker, Marco Valgimigli

Abstract

Introduction: The GLOBAL LEADERS is an open-label, pragmatic and superiority randomised controlled trial designed to challenge the current treatment paradigm of dual antiplatelet therapy (DAPT) for 12 months followed by aspirin monotherapy among patients undergoing percutaneous coronary intervention. By design, all study endpoints are investigator reported (IR) and not subject to formal adjudication by an independent Clinical Event Committee (CEC), which may introduce detection, reporting or ascertainment bias.

Methods and analysis: We designed the GLOBAL LEADERS Adjudication Sub-StudY (GLASSY) to prospectively implement, in a large sample of patients enrolled within the GLOBAL LEADERS trial (7585 of 15 991, 47.5%), an independent adjudication process of reported and unreported potential endpoints, using standardised CEC procedures, in order to assess whether 23-month ticagrelor monotherapy (90 mg twice daily) after 1-month DAPT is non-inferior to a standard regimen of DAPT for 12 months followed by aspirin monotherapy for the primary efficacy endpoint of death, non-fatal myocardial infarction, non-fatal stroke or urgent target vessel revascularisation and superior for the primary safety endpoint of type 3 or 5 bleeding according to the Bleeding Academic Research Consortium criteria.This study will comprehensively assess the comparative safety and efficacy of the two tested antithrombotic strategies on CEC-adjudicated ischaemic and bleeding endpoints and will provide insights into the role of a standardised CEC adjudication process on the interpretation of study findings by quantifying the level of concordance between IR-reported and CEC-adjudicated events.

Ethics and dissemination: GLASSY has been approved by local ethics committee of all study sites and/or by the central ethics committee for the country depending on country-specific regulations. In all cases, they deemed that it was not necessary to obtain further informed consent from individual subjects.

Trial registration number: NCT01813435.

Keywords: coronary heart disease; coronary intervention; ischaemic heart disease; myocardial infarction.

Conflict of interest statement

Competing interests: SL reports personal fees for advisory board participation from AstraZeneca, Chiesi and The Medicine Company. M Val reports grants from The Medicines Company, grants from Terumo, during the study; grants from AstraZeneca, and personal fees from Terumo, St Jude Vascular and Abbott Vascular, outside the submitted work.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
GLOBAL LEADERS design. ACS, acute coronary syndrome; ASA, aspirin; CAD, coronary artery disease; MI, myocardial infarction; PCI, percutaneous coronary intervention.
Figure 2
Figure 2
GLASSY design. CEC, Clinical Event Committee; GLASSY, GLOBAL LEADERS Adjudication Sub-StudY.

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