January 14th, 2022
ECRI announces the publication of the study protocol of the OPTIMAL trial, a multi-center, international, randomized, 2-year, parallel-group study to assess the superiority of IVUS-guided PCI versus qualitative angio-guided PCI in unprotected left main coronary artery (ULMCA) disease, in PLOS ONE.
Rotterdam, the Netherlands – the European Cardiovascular Research Institute (ECRI) announced today the publication of the study protocol of the OPTIMAL trial, in which Dr. Giovanni Luigi De Maria and the study leadership present a comprehensive description of the OPTIMAL trial background, its methods, statistical considerations, and imaging methods. In addition, and per requirements of PLOS ONE, a journal community that applies the Creative Commons Attribution (CC BY) license to works they publish, the full protocol of the OPTIMAL trial is now available online. Under the CC BY license, anyone may access, copy, distribute, or reuse these articles, as long as the author and original source are properly cited.
The OPTIMAL trial is a randomized, multicenter, international study designed to enroll a total of 800 patients undergoing percutaneous coronary intervention (PCI) for unprotected left main coronary artery (LMCA) disease. LMCA disease affects ~4% of patients undergoing PCI, and although not very frequent, it is among the most complex and high-risk coronary interventions, because the LMCA supplies blood to two thirds of the left ventricle and its disease usually affects its bifurcation, treatment of which increases the technical complexity.
Data from dedicated randomized clinical trials have highlighted the potential of PCI as mode of revascularization for unprotected LMCA (as an alternative to cardiac surgery), especially in patients with low to moderate degree of complexity of coronary anatomy or in patients unsuitable for cardiac surgery. This equipoise in terms of long-term mortality between PCI and cardiac surgery in unprotected LMCA disease has been recently confirmed in meta-analysis and long-term trial data. Moreover, in order to guarantee a durable result of PCI in the LMCA, that is able to match the proven outcomes from cardiac surgery, PCI has to be appropriately and meticulously planned, and the result has to be optimized. Currently two-dimensional angiography and/or intracoronary imaging (e.g. IVUS) are used to assess both the lumen, the features of the arterial wall, as well as optimal stent placement based on rigorous criteria.
Vast retrospective data and meta-analyses suggest that the use of IVUS may improve clinical outcomes after PCI in the LMCA, however, there is no prospective, randomized data that supports this observation. In OPTIMAL, patients are randomized in a 1:1 fashion to IVUS-guided PCI versus angiogram-guided PCI. In patients allocated to the IVUS guidance arm, pre-procedural IVUS assessment is highly recommended, whilst post-procedural IVUS assessment is mandatory to confirm appropriate stenting result and/or to guide stent result optimization, according to predefined criteria. Patients will be followed up to 2 years after the index procedure. The primary outcome measure is a patient-oriented composite endpoint following the standards of the Academic Research Consortium.
The study is overseen by a panel of renowned experts in cardiovascular research, including Prof. Adrian Banning (Study Chairman and Principal Investigator, John Radcliffe Hospital, Oxford, United Kingdom), Dr. Luca Testa (Deputy Chairman and Principal Investigator, IRCCS Policlinico S. Donato, Milan, Italy), Dr. José María de la Torre Hernández (National Lead Investigator, Hospital Universitario Marques de Valdecilla, Santander, Spain), Dr. Giovanni Luigi De Maria (National Lead Investigator, John Radcliffe Hospital, Oxford, United Kingdom), Dr. Francesco Bedogni (National Lead Investigator, IRCCS Policlinico S. Donato, Milan, Italy), and Dr. Ernest Spitzer (ECRI, Rotterdam, the Netherlands), as sponsor representative.
In 2021, OPTIMAL reached the “300 randomized patients’ milestone”, being a major step for a trial that targets 800 patients. The study leadership and the sponsor wish to recognize the extraordinary commitment of the Clinical Sites in 2021 in the United Kingdom, Spain, and Italy, who continuedly had to adapt to restrictions imposed by the pandemic and voluntarily stretched working hours. Likewise, the study leadership and the sponsor wish to recognize the outstanding work of the study team at Cardialysis, led by Graciëlle Schutjens (OPTIMAL Project Manager).
The OPTIMAL trial is possible through the financial support of two grant-givers, Boston Scientific and Philips Volcano, who joint this effort as funders through their respective investigator-initiated studies programs allowing to fund IIS through research grants, in observation of MedTech regulations. Passion and dedication of multi-disciplinary teams in this ambitious joint venture have been and are the cornerstone for the success of OPTIMAL. The OPTIMAL study will be the first and largest ever conducted clinical trial randomizing patients undergoing PCI to LMCA to IVUS-guidance versus angiography-guidance. Despite the widespread perception that IVUS-guidance can improve clinical outcomes, the evidence still comes from observational series or sub-analysis of other studies designed to address a different question.
ECRI is an independent organization, that brings together top clinical researchers and supporting industry in order to perform innovative and multinational investigator-initiated clinical studies that improve cardiovascular health care and to perform these clinical studies according to international regulations and within pre-defined budgets and timelines. Cardialysis (Rotterdam, The Netherlands), an expert cardiovascular research organization with almost 40 years of expertise, is responsible for trial services including trial & site management, regulatory submission, eCRF, data management, statistics, endpoint adjudication, as well as Core Laboratory activities.
Giovanni Luigi De Maria, Luca Testa, Jose M. de la Torre Hernandez, Dimitrios Terentes-Printzios, Maria Emfietzoglou, Roberto Scarsini, Francesco Bedogni, Ernest Spitzer, Adrian Banning. A multi-center, international, randomized, 2-year, parallel-group study to assess the superiority of IVUS-guided PCI versus qualitative angio-guided PCI in unprotected left main coronary artery (ULMCA) disease: Study protocol for OPTIMAL trial. PLoS One. 2022 Jan 7;17(1):e0260770. doi: 10.1371/journal.pone.0260770. eCollection 2022.