{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:24:27Z","timestamp":1779236667754,"version":"3.51.4"},"reference-count":0,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,10,27]],"date-time":"2020-10-27T00:00:00Z","timestamp":1603756800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,10,27]],"date-time":"2020-10-27T00:00:00Z","timestamp":1603756800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100011917","name":"Hormozgan University of Medical Sciences","doi-asserted-by":"publisher","award":["990233"],"award-info":[{"award-number":["990233"]}],"id":[{"id":"10.13039\/501100011917","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Trials"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n<jats:title>Objectives<\/jats:title>\n<jats:p>We will evaluate the efficacy and safety of favipiravir and interferon beta-1a compared to lopinavir\/ritonavir and interferon beta-1a in patients with confirmed COVID-19, who are moderately ill.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Trial design<\/jats:title>\n<jats:p>This is a phase 3, single-center, randomized, open-label, controlled trial with a parallel-group design carried out at Shahid Mohammadi Hospital, Bandar Abbas, Iran.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Participants<\/jats:title>\n<jats:p>All patients with age\u2009\u2265\u200920\u2009years admitted at the Severe Acute Respiratory Syndrome Departments of the Shahid Mohammadi Hospital, Bandar Abbas, Iran, will be screened for the following criteria.<\/jats:p>\n<jats:p><jats:italic>Inclusion criteria<\/jats:italic>:\n<jats:list list-type=\"order\">\n\n\n<jats:list-item>\n<jats:p>Confirmed diagnosis of infection with SARS-CoV-2 using polymerase chain reaction and\/or antibody tests.<\/jats:p>\n<\/jats:list-item>\n\n\n\n<jats:list-item>\n<jats:p>Moderate COVID-19 pneumonia (via computed tomography and\/or X-ray imaging), requiring hospitalization.<\/jats:p>\n<\/jats:list-item>\n\n\n\n<jats:list-item>\n<jats:p>Hospitalized \u2264\u200948\u2009h.<\/jats:p>\n<\/jats:list-item>\n\n\n\n<jats:list-item>\n<jats:p>Signing informed consent and willingness of the participant to accept randomization to any assigned treatment arm.<\/jats:p>\n<\/jats:list-item>\n\n<\/jats:list><\/jats:p>\n<jats:p><jats:italic>Exclusion criteria<\/jats:italic>:\n<jats:list list-type=\"order\">\n\n\n<jats:list-item>\n<jats:p>Underlying conditions, including chronic hepatitis, cirrhosis, cholestatic liver diseases, cholecystitis, peptic ulcers, acute and chronic renal failure, and peptic ulcers.<\/jats:p>\n<\/jats:list-item>\n\n\n\n<jats:list-item>\n<jats:p>Severe and critical COVID-19 pneumonia.<\/jats:p>\n<\/jats:list-item>\n\n\n\n<jats:list-item>\n<jats:p>History of allergy to favipiravir, lopinavir\/ritonavir, and interferon beta-1a.<\/jats:p>\n<\/jats:list-item>\n\n\n\n<jats:list-item>\n<jats:p>Pregnancy and breastfeeding.<\/jats:p>\n<\/jats:list-item>\n\n<\/jats:list><\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Intervention and comparator<\/jats:title>\n<jats:p><jats:italic>Intervention group<\/jats:italic>: favipiravir (Zhejiang Hisun, China) with interferon beta-1a (CinnaGen, Iran). This group will receive 1600\u2009mg favipiravir twice a day for the first day and 600\u2009mg twice a day for the following 4\u00a0days with five doses of 44\u00a0mcg interferon beta-1a every other day.<\/jats:p>\n<jats:p><jats:italic>Control group<\/jats:italic>: lopinavir\/ritonavir (Heterd Company, India) with interferon beta-1a (CinnaGen, Iran). This group will receive 200\/50\u2009mg lopinavir\/ritonavir twice a day for 7\u00a0days with five doses of 44\u00a0mcg interferon beta-1a every other day.<\/jats:p>\n<jats:p>Other supportive and routine care will be the same in both groups.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Main outcomes<\/jats:title>\n<jats:p>The primary outcome of the trial is the viral load of SARS-CoV-2 in the nasopharyngeal samples assessed by RT-PCR after 7\u00a0days of randomization as well as clinical improvement of fever and O<jats:sub>2<\/jats:sub> saturation within 7\u00a0days of randomization.<\/jats:p>\n<jats:p>The secondary outcomes are the length of hospital stay and the incidence of serious adverse drug reactions within 7\u00a0days of randomization.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Randomization<\/jats:title>\n<jats:p>Eligible patients will be allocated to one of the study arms using block randomization in a 1:1 ratio (each block consists of 10 patients). A web-based system will be used to generate random numbers for the allocation sequence. Each number relates to one of the study arms.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Blinding (masking)<\/jats:title>\n<jats:p>This is an open-label trial without blinding and placebo control.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Numbers to be randomized (sample size)<\/jats:title>\n<jats:p>A total of 60 patients will be randomized into two groups (30 patients in the intervention group and 30 patients in the control group).<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Trial status<\/jats:title>\n<jats:p>The trial protocol is version 1.0, 22 July 2020. Recruitment began on 25 July 2020 and is anticipated to be completed by 25 September 2020.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Trial registration<\/jats:title>\n<jats:p>Iranian Registry of Clinical Trials (IRCT) <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.irct.ir\/trial\/49463\">IRCT20200506047323N3<\/jats:ext-link>. Registered on 22 July 2020.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Full protocol<\/jats:title>\n<jats:p>The full protocol is attached as an additional file, accessible from the <jats:italic>Trials<\/jats:italic> website (Additional file 1). In the interest in expediting the dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s13063-020-04747-8","type":"journal-article","created":{"date-parts":[[2020,10,27]],"date-time":"2020-10-27T07:03:14Z","timestamp":1603782194000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Evaluation of the efficacy and safety of favipiravir and interferon compared to lopinavir\/ritonavir and interferon in moderately ill patients with COVID-19: a structured summary of a study protocol for a randomized controlled trial"],"prefix":"10.1186","volume":"21","author":[{"given":"Mehdi","family":"Hassaniazad","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Bazram","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soheil","family":"Hassanipour","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4568-7024","authenticated-orcid":false,"given":"Mohammad","family":"Fathalipour","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,10,27]]},"container-title":["Trials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-020-04747-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13063-020-04747-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-020-04747-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T23:29:02Z","timestamp":1635290942000},"score":1,"resource":{"primary":{"URL":"https:\/\/trialsjournal.biomedcentral.com\/articles\/10.1186\/s13063-020-04747-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,27]]},"references-count":0,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["4747"],"URL":"https:\/\/doi.org\/10.1186\/s13063-020-04747-8","relation":{},"ISSN":["1745-6215"],"issn-type":[{"value":"1745-6215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,27]]},"assertion":[{"value":"10 September 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 September 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 October 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The RCT protocol was approved by the Ethics Committee of Hormozgan University of Medical Sciences (Ethics Committee reference number: ) on 21 July 2020. The investigators declare the trial has received ethical approval from the appropriate ethical committee, as described above. All participants freely signed informed consent before randomization.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"886"}}