{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:38:09Z","timestamp":1792798689848,"version":"4.5.0"},"reference-count":13,"publisher":"BMJ","issue":"11","funder":[{"name":"Funda\u00e7\u00e3o Faculdade de Medicina USP","id":[{"id":"https:\/\/ror.org\/03mhtag13","id-type":"ROR","asserted-by":"crossref"}]},{"name":"FAPESP, S\u00e3o Paulo Foundation for Research","award":["2016\/01735-2"],"award-info":[{"award-number":["2016\/01735-2"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2019,9,18]]},"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>An ongoing outbreak of yellow fever (YF) has been reported in Brazil with 1261 confirmed cases and 409 deaths since July 2017. To date, there is no specific treatment available for YF. Recently published papers describing in vitro and animal models suggest a potential effect of antiviral drugs (approved for the treatment of hepatitis virus) against flaviviruses, including YF. The primary aim of this study is to analyse the effect of sofosbuvir on viral kinetics and clinical outcomes among patients presenting with YF. This is a multicentre open-label randomised controlled trial with 1:1 individual allocation, stratified by severity and by recruiting centre.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>Adults with suspected or confirmed YF infection and symptoms lasting up to 15 days are screened. Eligible and consenting patients are randomised to receive oral sofosbuvir 400\u2009mg daily for 10 days or to receive standard clinical care. Viral kinetics are measured daily and the reduction in YF plasma viral load from the sample at inclusion to 72\u2009hours after randomisation will be compared between active and control groups. Clinical outcomes include severity meeting criteria for intensive care support, liver transplantation, in-hospital mortality and mortality within 60 days.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>Ethics approval was obtained at the participating sites and at the national research ethics committee (CAAE 82673018.6.1001.0068). The trial has been submitted for ethical approval at additional potential recruiting centres. Results of the study will be published in journals and presented at scientific meetings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>Brazilian Clinical Trials Registry (RBR-93dp9n).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2018-027207","type":"journal-article","created":{"date-parts":[[2019,11,26]],"date-time":"2019-11-26T05:54:13Z","timestamp":1574747653000},"page":"e027207","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":20,"title":["Efficacy of sofosbuvir as treatment for yellow fever: protocol for a randomised controlled trial in Brazil (SOFFA study)"],"prefix":"10.1136","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6264-5395","authenticated-orcid":false,"given":"Claudia","family":"Figueiredo-Mello","sequence":"first","affiliation":[{"name":"Department of Education and Research, Instituto de Infectologia Emilio Ribas, Sao Paulo, SP, Brazil"},{"name":"Department of Infectious and Parasitic Diseases, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8341-8960","authenticated-orcid":false,"given":"Luciana Vilas Boas","family":"Casadio","sequence":"additional","affiliation":[{"name":"Department of Infectious and Parasitic Diseases, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil"},{"name":"Department of Gastroenterology (LIM07), Faculdade de Medicina FMUSP, Universidade de S\u00e3o Paulo, Sao Paulo, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivian Iida","family":"Avelino-Silva","sequence":"additional","affiliation":[{"name":"Department of Infectious and Parasitic Diseases, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8719-2508","authenticated-orcid":false,"given":"Ho","family":"Yeh-Li","sequence":"additional","affiliation":[{"name":"Department of Infectious and Parasitic Diseases, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaques","family":"Sztajnbok","sequence":"additional","affiliation":[{"name":"Medical Division-Intensive Care Unit, Instituto de Infectologia Emilio Ribas, Sao Paulo, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Joelsons","sequence":"additional","affiliation":[{"name":"Department of Infectious and Parasitic Diseases, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilia Bordignon","family":"Antonio","sequence":"additional","affiliation":[{"name":"Department of Infectious and Parasitic Diseases, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3999-0489","authenticated-orcid":false,"given":"Jo\u00e3o Renato Rebello","family":"Pinho","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology (LIM07), Faculdade de Medicina FMUSP, Universidade de S\u00e3o Paulo, Sao Paulo, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8887-5060","authenticated-orcid":false,"given":"Fernanda de Mello","family":"Malta","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology (LIM07), Faculdade de Medicina FMUSP, Universidade de S\u00e3o Paulo, Sao Paulo, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5932-2360","authenticated-orcid":false,"given":"Michele Soares","family":"Gomes-Gouv\u00eaa","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology (LIM07), Faculdade de Medicina FMUSP, Universidade de S\u00e3o Paulo, Sao Paulo, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4205-9401","authenticated-orcid":false,"given":"Ana Paula Moreira","family":"Salles","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology (LIM07), Faculdade de Medicina FMUSP, Universidade de S\u00e3o Paulo, Sao Paulo, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline Pivetta","family":"Cor\u00e1","sequence":"additional","affiliation":[{"name":"Clinical Lab, Instituto de Infectologia Emilio Ribas, Sao Paulo, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Henrique Valente","family":"Moreira","sequence":"additional","affiliation":[{"name":"Inpatient Unit, Instituto de Infectologia Emilio Ribas, Sao Paulo, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Freitas","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Epidemiology Service, Instituto de Infectologia Emilio Ribas, Sao Paulo, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5415-6156","authenticated-orcid":false,"given":"Ana Catharina de Seixas Santos","family":"Nastri","sequence":"additional","affiliation":[{"name":"Department of Infectious and Parasitic Diseases, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil"},{"name":"Department of Gastroenterology (LIM07), Faculdade de Medicina FMUSP, Universidade de S\u00e3o Paulo, Sao Paulo, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ceila Maria Sant'Ana","family":"Malaque","sequence":"additional","affiliation":[{"name":"Medical Division-Intensive Care Unit, Instituto de Infectologia Emilio Ribas, Sao Paulo, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralcyon Francis Azevedo","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Medical Division, Instituto de Infectologia Emilio Ribas, Sao Paulo, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana Marques Sans\u00e3o","family":"Borges","sequence":"additional","affiliation":[{"name":"Medical Emergency Department, Instituto de Infectologia Emilio Ribas, Sao Paulo, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario Periba\u00f1ez","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Outpatients Clinic, Instituto de Infectologia Emilio Ribas, Sao Paulo, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiz Carlos Pereira","family":"Junior","sequence":"additional","affiliation":[{"name":"Technical Department, Instituto de Infectologia Emilio Ribas, Sao Paulo, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T\u00e2mara Newman Lobato","family":"Souza","sequence":"additional","affiliation":[{"name":"ER and Outpatient Service, Instituto de Infectologia Emilio Ribas, Sao Paulo, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6992-9326","authenticated-orcid":false,"given":"Alice Tung Wan","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiz Augusto Carneiro","family":"D'Albuquerque","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edson","family":"Abdala","sequence":"additional","affiliation":[{"name":"Department of Infectious and Parasitic Diseases, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil"},{"name":"Infectious Diseases, Universidade de Sao Paulo Instituto do Cancer do Estado de Sao Paulo, Sao Paulo, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5162-138X","authenticated-orcid":false,"given":"Wellington","family":"Andraus","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo Bronze de","family":"Martino","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana","family":"Ducatti","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilherme Marques","family":"Andrade","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiz Marcelo S\u00e1","family":"Malbouisson","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izabel Marcilio de","family":"Souza","sequence":"additional","affiliation":[{"name":"Epidemiologic Surveillance Department, Universidade de S\u00e3o Paulo Hospital das Cl\u00ednicas, Sao Paulo, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flair Jos\u00e9","family":"Carrilho","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2623-5126","authenticated-orcid":false,"given":"Ester Cerdeira","family":"Sabino","sequence":"additional","affiliation":[{"name":"Department of Infectious and Parasitic Diseases, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna S","family":"Levin","sequence":"additional","affiliation":[{"name":"Department of Infectious and Parasitic Diseases, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2019,11,25]]},"reference":[{"key":"2025121222060894000_9.11.e027207.1","unstructured":"Minist\u00e9rio da Sa\u00fade . Monitoramento do Per\u00edodo Sazonal dA Febre Amarela Brasil 2017-2018. Available: http:\/\/portalarquivos2.saude.gov.br\/images\/pdf\/2018\/maio\/09\/Informe-FA.pdf [Accessed 26 Sep 2018]."},{"key":"2025121222060894000_9.11.e027207.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2014.08.030"},{"key":"2025121222060894000_9.11.e027207.3","doi-asserted-by":"publisher","DOI":"10.1038\/srep41926"},{"key":"2025121222060894000_9.11.e027207.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2016.11.023"},{"key":"2025121222060894000_9.11.e027207.5","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0007072","article-title":"Yellow fever virus is susceptible to sofosbuvir both in vitro and in vivo","volume":"13","author":"de Freitas","year":"2019","journal-title":"PLoS Negl Trop Dis"},{"key":"2025121222060894000_9.11.e027207.6","doi-asserted-by":"publisher","DOI":"10.1038\/srep41926"},{"key":"2025121222060894000_9.11.e027207.7","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1016\/j.aohep.2019.09.001","article-title":"Sofosbuvir inhibits yellow fever virus in vitro and in patients with acute liver failure","volume":"18","author":"Mendes","year":"2019","journal-title":"Ann Hepatol"},{"key":"2025121222060894000_9.11.e027207.8","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2002.31250"},{"key":"2025121222060894000_9.11.e027207.9","unstructured":"Sealed Envelope Ltd . Create a blocked randomisation list, 2017. Available: https:\/\/www.sealedenvelope.com\/simple-randomiser\/v1\/lists [Accessed 8 May 2018]."},{"key":"2025121222060894000_9.11.e027207.10","doi-asserted-by":"crossref","first-page":"4001","DOI":"10.1016\/j.jchromb.2009.10.013","article-title":"Highly sensitive determination of HCV protease inhibitors boceprevir (SCH 503034) and telaprevir (VX 950) in human plasma by LC\u2013MS\/MS","volume":"877","author":"Farnik","year":"2009","journal-title":"Journal of Chromatography B"},{"key":"2025121222060894000_9.11.e027207.11","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.865"},{"key":"2025121222060894000_9.11.e027207.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbi.2008.08.010"},{"key":"2025121222060894000_9.11.e027207.13","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-158-3-201302050-00583"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2018-027207","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T06:06:18Z","timestamp":1765605978000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2018-027207"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11]]},"references-count":13,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2019,11,25]]},"published-print":{"date-parts":[[2019,11]]}},"alternative-id":["10.1136\/bmjopen-2018-027207"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2018-027207","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11]]}}}