{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T04:07:13Z","timestamp":1793851633903,"version":"4.6.1"},"reference-count":79,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":2031,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>There is broad interest in improved methods to generate robust evidence regarding best practice, especially in settings where patient conditions are heterogenous and require multiple concomitant therapies. Here, we present the rationale and design of a large, international trial that combines features of adaptive platform trials with pragmatic point-of-care trials to determine best treatment strategies for patients admitted to an intensive care unit with severe community-acquired pneumonia. The trial uses a novel design, entitled \u201ca randomized embedded multifactorial adaptive platform.\u201d The design has five key features: 1) randomization, allowing robust causal inference; 2) embedding of study procedures into routine care processes, facilitating enrollment, trial efficiency, and generalizability; 3) a multifactorial statistical model comparing multiple interventions across multiple patient subgroups; 4) response-adaptive randomization with preferential assignment to those interventions that appear most favorable; and 5) a platform structured to permit continuous, potentially perpetual enrollment beyond the evaluation of the initial treatments. The trial randomizes patients to multiple interventions within four treatment domains: antibiotics, antiviral therapy for influenza, host immunomodulation with extended macrolide therapy, and alternative corticosteroid regimens, representing 240 treatment regimens. The trial generates estimates of superiority, inferiority, and equivalence between regimens on the primary outcome of 90-day mortality, stratified by presence or absence of concomitant shock and proven or suspected influenza infection. The trial will also compare ventilatory and oxygenation strategies, and has capacity to address additional questions rapidly during pandemic respiratory infections. As of January 2020, REMAP-CAP (Randomized Embedded Multifactorial Adaptive Platform for Community-acquired Pneumonia) was approved and enrolling patients in 52 intensive care units in 13 countries on 3 continents. In February, it transitioned into pandemic mode with several design adaptations for coronavirus disease 2019. Lessons learned from the design and conduct of this trial should aid in dissemination of similar platform initiatives in other disease areas.<\/jats:p>\n                  <jats:p>Clinical trial registered with www.clinicaltrials.gov (NCT02735707).<\/jats:p>","DOI":"10.1513\/annalsats.202003-192sd","type":"journal-article","created":{"date-parts":[[2020,4,8]],"date-time":"2020-04-08T12:20:40Z","timestamp":1586348440000},"page":"879-891","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":404,"title":["The REMAP-CAP (Randomized Embedded Multifactorial Adaptive Platform for Community-acquired Pneumonia) Study. Rationale and Design"],"prefix":"10.1093","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7026-5181","authenticated-orcid":false,"given":"Derek C.","family":"Angus","sequence":"first","affiliation":[{"name":"The Clinical Research Investigation and Systems Modeling of Acute Illness Center, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Berry","sequence":"additional","affiliation":[{"name":"Berry Consultants, LLC, Austin, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0020-4869","authenticated-orcid":false,"given":"Roger J.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Berry Consultants, LLC, Austin, Texas"},{"name":"Department of Emergency Medicine, Harbor\u2013University of California Los Angeles (UCLA) Medical Center, Torrance, California"},{"name":"Department of Emergency Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4701-463X","authenticated-orcid":false,"given":"Farah","family":"Al-Beidh","sequence":"additional","affiliation":[{"name":"Division of Anaesthetics, Pain Medicine and Intensive Care Medicine, Department of Surgery and Cancer, Imperial College London and Imperial College Healthcare National Health Service Trust, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaseen","family":"Arabi","sequence":"additional","affiliation":[{"name":"Intensive Care Department, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, King Abdulaziz Medical City, Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilma","family":"van Bentum-Puijk","sequence":"additional","affiliation":[{"name":"Julius Center for Health Sciences and Primary Care"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahra","family":"Bhimani","sequence":"additional","affiliation":[{"name":"Li Ka Shing Knowledge Institute, St. Michael\u2019s Hospital, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Bonten","sequence":"additional","affiliation":[{"name":"Julius Center for Health Sciences and Primary Care"},{"name":"Department of Medical Microbiology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristine","family":"Broglio","sequence":"additional","affiliation":[{"name":"Berry Consultants, LLC, Austin, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8132-8651","authenticated-orcid":false,"given":"Frank","family":"Brunkhorst","sequence":"additional","affiliation":[{"name":"Center for Clinical 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