Effectiveness of glucocorticoid therapy in patients with severe coronavirus disease 2019: protocol of a randomized controlled trial

Abstract

Background: At the end of 2019, a novel coronavirus outbreak emerged in Wuhan, China, and its causative organism has been subsequently designated the 2019 novel coronavirus (2019-nCoV). The effectiveness of adjunctive glucocorticoid therapy in the management of 2019-nCoV-infected patients with severe lower respiratory tract infections is not clear, and warrants further investigation. Methods: The present study will be conducted as an open-labeled, randomized, controlled trial. We will enrol 48 subjects from Chongqing Public Health Medical Center. Each eligible subject will be assigned to an intervention group (methylprednisolone via intravenous injection at a dose of 1-2 mg/kg/day for 3 days) or a control group (no glucocorticoid use) randomly, at a 1:1 ratio. Subjects in both groups will be invited for 28 days of follow-up which will be scheduled at four consecutive visit points. We will use the clinical improvement rate as our primary endpoint. Secondary endpoints include the timing of clinical improvement after intervention, duration of mechanical ventilation, duration of hospitalization, overall incidence of adverse events, as well as rate of adverse events at each visit, and mortality at 2 and 4 weeks. Discussion: The present coronavirus outbreak is the third serious global coronavirus outbreak in the past two decades. Oral and parenteral glucocorticoids have been used in the management of severe respiratory symptoms in coronavirus-infected patients in the past. However, there remains no definitive evidence in the literature for or against the utilization of systemic glucocorticoids in seriously ill patients with coronavirus-related severe respiratory disease, or indeed in other types of severe respiratory disease. In this study, we hope to discover evidence either supporting or opposing the systemic therapeutic administration of glucocorticoids in patients with severe coronavirus disease 2019. Trial registration: ClinicalTrials.gov, ChiCTR2000029386, http://www.chictr.org.cn/showproj.aspx?proj=48777.

Use of Corticosteroids in Coronavirus Disease 2019 Pneumonia: A Systematic Review of the Literature

“…As shown in Figure 1, among 31 initially included studies (14 in English and 17 in Chinese), eight were reviewed as full-text and four finally included (14)(15)(16)(17). Two studies were excluded since they were commentaries (9, 10), one excluded as it was a protocol (18), and one a letter to Editor (19). Table 1 shows the descriptive characteristics of the four included studies.…”

“…Importantly, one study identified in this review in patients with ARDS owing to COVID-19 infection showed that methylprednisolone significantly decreased the risk of mortality. It should be noted that there is currently one ongoing clinical trial that is directly addressing this research question and its results are eagerly awaited (18).…”

COVID-19 Pandemic: an Overview of epidemiology, pathogenesis, Diagnostics and Potential Vaccines and Therapeutics

“…Ongoing clinical trials are being conducted at this moment to confirm their role. ChiCTR2000029386 is a randomized clinical trial currently being conducted in China on 48 patients and methylprednisolone to be administrated to half of them like a dose of 1-2 mg/kg/day for 3 days [123]. Other studies also registered for Clinicaltrials.gov and currently in the process of recruiting patients.…”

Can melatonin reduce the severity of COVID-19 pandemic?

“…Currently, the following drugs are most often used to treat coronavirus infection: the combination of the antiviral drugs lopinavir/ritonavir [68], nucleotide analogs that inhibit RNA-dependent-RNA polymerize of the virusribavirin [69] and remdesivir [70], antimalarial drug hydroxychloroquine (less toxic analog of chloroquine) [71], sometimes in combination with the antibiotic azithromycin [72], and the glucocorticoid methylprednisolone [73]. According to a recent study on lopinavir/ritonavir, the combination of drugs used to treat AIDS did not show any benefits compared to standard hospitalization [74].…”