{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T11:33:11Z","timestamp":1775561591355,"version":"3.50.1"},"reference-count":23,"publisher":"Cambridge University Press (CUP)","issue":"1","license":[{"start":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T00:00:00Z","timestamp":1698710400000},"content-version":"unspecified","delay-in-days":303,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Trans. Sci."],"published-print":{"date-parts":[[2023]]},"abstract":"<jats:title>Abstract<\/jats:title>\n\t  <jats:p>Despite the availability of vaccinations, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to cause Coronavirus Disease 2019 (COVID-19) infection with a spectrum of disease in the acute setting. Transmission, infection, and severe disease remain common. There is a critical need to establish treatment regimens in the ambulatory setting that can reduce symptom burden and potentially prevent progression to severe disease and death. Many existing medicines previously approved for other uses may have benefit but remain unproven in informative clinical trials.<\/jats:p>\n\t  <jats:p>Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV)-6 is a decentralized, placebo-controlled, double-blind, randomized, platform trial that has now enrolled more than 7500 participants and has reported on the effectiveness of ivermectin at two doses, fluticasone, and fluvoxamine for helping people with COVID-19. With additional repurposed therapies added to the platform, ACTIV-6 continues to enroll symptomatic outpatients aged \u2265 30 years with a confirmed positive PCR or antigen test for SARS-CoV-2. Potential participants are screened and enrolled online, through a call center, or facilitated by local study sites. Participants consent electronically and are randomized to placebo or to one of the open study drugs for which they are eligible at the time of enrollment. A shared, contemporary placebo approach is used. Participants receive study drug in the mail and remain on study for up to 180 days. While enrolled, electronic patient-reported outcome assessments are used to monitor symptoms, healthcare utilization, and mortality. The primary endpoint is time to recovery or a composite of hospitalization and mortality within 28 days. Symptoms, acute healthcare utilization, and the Patient-Reported Outcomes Measurement Information System-29 are collected for up to 180 days.<\/jats:p>\n\t  <jats:p>Using a decentralized trial approach allowed the ACTIV-6 platform to increase both reach and rate of enrollment. The decentralized approach did not simplify regulatory oversight, and we found unanticipated challenges in patient behavior and the study drug delivery process. Despite challenges, ACTIV-6 has enrolled thousands of participants from across the USA and continues to test the effectiveness of repurposed medicines for treating COVID-19. Our lessons learned contribute to the emerging understanding of how to optimize decentralized trials.<\/jats:p>","DOI":"10.1017\/cts.2023.644","type":"journal-article","created":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T11:39:11Z","timestamp":1698752351000},"source":"Crossref","is-referenced-by-count":13,"title":["ACTIV-6: Operationalizing a decentralized, outpatient randomized platform trial to evaluate efficacy of repurposed medicines for COVID-19"],"prefix":"10.1017","volume":"7","author":[{"name":"The Accelerating Covid-19 Therapeutic Interventions and Vaccines (ACTIV)-6 Study Group","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"56","published-online":{"date-parts":[[2023,10,31]]},"reference":[{"key":"S2059866123006441_ref7","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.8920"},{"key":"S2059866123006441_ref14","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.1650"},{"key":"S2059866123006441_ref22","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm7104e2"},{"key":"S2059866123006441_ref15","unstructured":"15. U.S. Food and Drug Administration. COVID-19: Developing Drugs and Biological Products for Treatment or Prevention. Published June 23, 2021. (https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/covid-19-developing-drugs-and-biological-products-treatment-or-prevention). Accessed April 27, 2022."},{"key":"S2059866123006441_ref3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2118542"},{"key":"S2059866123006441_ref4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2116044"},{"key":"S2059866123006441_ref18","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.625678"},{"key":"S2059866123006441_ref19","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2021.100959"},{"key":"S2059866123006441_ref23","doi-asserted-by":"publisher","DOI":"10.1007\/s42399-022-01167-4"},{"key":"S2059866123006441_ref1","unstructured":"1. Center for Systems Science and Engineering at Johns Hopkins University. Coronavirus COVID-19 (2019-nCoV). (https:\/\/www.arcgis.com\/apps\/dashboards\/bda7594740fd40299423467b48e9ecf6). Accessed May 11, 2023."},{"key":"S2059866123006441_ref9","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000005295"},{"key":"S2059866123006441_ref6","unstructured":"6. National Institutes of Health. Immunomodulators Summary Recommendations. COVID-19 Treatment Guidelines. (https:\/\/www.covid19treatmentguidelines.nih.gov\/therapies\/immunomodulators\/summary-recommendations\/). Accessed April 15, 2022."},{"key":"S2059866123006441_ref12","doi-asserted-by":"publisher","DOI":"10.1101\/2022.07.12.22277548"},{"key":"S2059866123006441_ref16","unstructured":"16. World Health Organization. COVID-19 Therapeutic Trial Synopsis. (https:\/\/cdn.who.int\/media\/docs\/default-source\/blue-print\/covid-19-therapeutic-trial-synopsis.pdf?sfvrsn=44b83344_1&download=true). Accessed February 18, 2020."},{"key":"S2059866123006441_ref5","unstructured":"5. U.S. Food and Drug Administration. Coronavirus (COVID-19) | Drugs. Published March 31, 2022. (https:\/\/www.fda.gov\/drugs\/emergency-preparedness-drugs\/coronavirus-covid-19-drugs). Accessed April 15, 2022."},{"key":"S2059866123006441_ref17","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2010.04.011"},{"key":"S2059866123006441_ref13","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2022.24100"},{"key":"S2059866123006441_ref8","doi-asserted-by":"publisher","DOI":"10.7326\/M21-1269"},{"key":"S2059866123006441_ref2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2007764"},{"key":"S2059866123006441_ref11","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2022.18590"},{"key":"S2059866123006441_ref21","unstructured":"21. Centers for Disease Control and Prevention. COVID Data Tracker. Published March 28, 2020. (https:\/\/covid.cdc.gov\/covid-data-tracker). Accessed July 27, 2021."},{"key":"S2059866123006441_ref20","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkz524"},{"key":"S2059866123006441_ref10","article-title":"The ACTIV-6 stakeholder advisory committee: a model for virtual engagement in decentralized clinical trials","author":"Hamm","journal-title":"J Clin Transl Sci"}],"container-title":["Journal of Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S2059866123006441","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T11:39:17Z","timestamp":1698752357000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S2059866123006441\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023]]},"references-count":23,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023]]}},"alternative-id":["S2059866123006441"],"URL":"https:\/\/doi.org\/10.1017\/cts.2023.644","relation":{},"ISSN":["2059-8661"],"issn-type":[{"value":"2059-8661","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023]]},"article-number":"e221"}}