{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T01:18:58Z","timestamp":1773623938969,"version":"3.50.1"},"reference-count":0,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,10,26]],"date-time":"2020-10-26T00:00:00Z","timestamp":1603670400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,10,26]],"date-time":"2020-10-26T00:00:00Z","timestamp":1603670400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Trials"],"published-print":{"date-parts":[[2020,12]]},"abstract":"Abstract<\/jats:title>\nObjectives<\/jats:title>\nWe will investigate the effectiveness of high dose Interferon Beta 1a, compared to low dose Interferon Beta 1a (the base therapeutic regimen) in COVID-19 Confirmed Cases (Either RT-PCR or CT Scan Confirmed) with moderate to severe disease<\/jats:p>\n<\/jats:sec>\nTrial Design<\/jats:title>\nThis is a single center, open label, randomized, controlled, 2-arm parallel group (1:1 ratio), clinical trial.<\/jats:p>\n<\/jats:sec>\nParticipants<\/jats:title>\nThe eligibility criteria in this study is: age \u2265 18 years, oxygen saturation (SPO2) \u2264 93% or respiratory rate \u2265 24, at least one of the following manifestation: radiation contactless body temperature \u226537.8, Cough, shortness of breath, nasal congestion\/ discharge, myalgia\/arthralgia, diarrhea\/vomiting, headache or fatigue on admission. The onset of the symptoms should be acute (\u2264 14 days). The exclusion criteria include refusal to participate, using drugs with potential interaction with lopinavir\/ritonavir or interferon-\u03b2 1a, blood ALT\/AST levels > 5 times the upper limit of normal on laboratory results, pregnant or lactating women, history of alcohol or drug addiction in the past 5 years, the patients who be intubated less than one hours after admission to hospital.<\/jats:p>\nThis study will be undertaken at the Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences.<\/jats:p>\n<\/jats:sec>\nIntervention and Comparator<\/jats:title>\nCOVID- 19 confirmed patients (using the RT-PCR test or CT scan) will be randomly assigned to one of two groups. The intervention group (Arms1) will be treated with lopinavir \/ ritonavir (Kaletra) + high dose Interferon-\u03b2 1a (Recigen) and the control group will be treated with lopinavir \/ ritonavir (Kaletra) + low dose Interferon-\u03b2 1a (Recigen) (the base therapeutic regimen). Both groups will receive standard care consisting of the necessary oxygen support, non-invasive, or invasive mechanical ventilation.<\/jats:p>\n<\/jats:sec>\nMain outcomes<\/jats:title>\nPrimary outcome: Time to clinical improvement is our primary outcome measure. This is an improvement of two points on a seven-category ordinal scale (recommended by the World Health Organization: Coronavirus disease (COVID-2019) R&D. Geneva: World Health Organization) or discharge from the hospital, whichever comes first.<\/jats:p>\nSecondary outcomes: mortality from the date of randomization until the last day of the study which will be the day all of the patients have had at least one of the following outcomes: 1) Improvement of two points on a seven-category ordinal scale. 2) Discharge from the hospital 3) Death. Improvement of SPO2 during the hospitalization, duration of hospitalization from date of randomization until the date of hospital discharge or death, whichever comes first. The incidence of new mechanical ventilation uses from the date of randomization until the last day of the study and the duration of it will be extracted. Please note that we are trying to add further secondary outcomes and this section of the protocol is still evolving.<\/jats:p>\n<\/jats:sec>\nRandomization<\/jats:title>\nEligible patients with confirmed SARS-Cov-2 infections will be randomly assigned in a 1:1 ratio to two therapeutic arms using permuted, block-randomization to balance the number of patients allocated to each group. The permuted block (three or six patients per block) randomization sequence will be generated, using Package \u2018randomizeR\u2019 in R software version 3.6.1. and placed in individual sealed and opaque envelopes by the statistician. The investigator will enroll the patients and only then open envelopes to assign patients to the different treatment groups. This method of allocation concealment will result in minimum selection and confounding biases.<\/jats:p>\n<\/jats:sec>\nBlinding (Masking)<\/jats:title>\nThe present research is open-label (no masking) of patients and health care professionals who are undertaking outcome assessment of the primary outcome - time to clinical improvement.<\/jats:p>\n<\/jats:sec>\nNumbers to be randomised (sample size)<\/jats:title>\nOf the 100 patients randomised, 50 patients will be assigned to receive high dose Interferon beta-1a plus lopinavir\/ritonavir (Kaletra), 50 patients will be assigned to receive low dose Interferon beta 1a plus lopinavir\/ritonavir (Kaletra).<\/jats:p>\n<\/jats:sec>\nTrial Status<\/jats:title>\nProtocol version 1.2.1. Recruitment is finished, the start date of recruitment was on August 20th<\/jats:sup> 2020, and the end date was on September 4th<\/jats:sup> 2020. Last point of data collection will be the last day on which all of the 100 participants have had an outcome of clinical improvement or death, up to 14th days after hospitalization.<\/jats:p>\n<\/jats:sec>\nTrial registration<\/jats:title>\nThis study was registered with National Institutes of Health Clinical trials (www.clinicaltrials.gov<\/jats:ext-link>; identification number NCT04521400, https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04521400<\/jats:ext-link>, registered August 18, 2020 and first available online August 20, 2020).<\/jats:p>\n<\/jats:sec>\nFull protocol<\/jats:title>\nThe full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting 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\/s13063-020-04812-2","type":"journal-article","created":{"date-parts":[[2020,10,26]],"date-time":"2020-10-26T08:03:05Z","timestamp":1603699385000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["An investigation into the beneficial effects of high-dose interferon beta 1-a, compared to low-dose interferon beta 1-a (the base therapeutic regimen) in moderate to severe COVID-19: A structured summary of a study protocol for a randomized controlled l trial"],"prefix":"10.1186","volume":"21","author":[{"given":"Ilad","family":"Alavi Darazam","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Firouze","family":"Hatami","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad Mahdi","family":"Rabiei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamad Amin","family":"Pourhoseingholi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Omid","family":"Moradi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shervin","family":"Shokouhi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad Reza","family":"Hajesmaeili","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minoosh","family":"Shabani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seyed Sina Naghibi","family":"Irvani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,10,26]]},"container-title":["Trials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-020-04812-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13063-020-04812-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-020-04812-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,25]],"date-time":"2021-10-25T23:24:28Z","timestamp":1635204268000},"score":1,"resource":{"primary":{"URL":"https:\/\/trialsjournal.biomedcentral.com\/articles\/10.1186\/s13063-020-04812-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,26]]},"references-count":0,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["4812"],"URL":"https:\/\/doi.org\/10.1186\/s13063-020-04812-2","relation":{},"ISSN":["1745-6215"],"issn-type":[{"value":"1745-6215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,26]]},"assertion":[{"value":"13 October 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 October 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 October 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The present study was approved by the Ethics in Medical Research Committee of the Shahid Beheshti University of Medical Sciences with an Approval number of IR.SBMU.RETECH.REC.1399.033. I certify that we will also obtain informed consent from all participants to participate in the study. The informed consent form is available in Farsi from the corresponding author on request.","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":"880"}}