Efficacy and Safety of Inhaled Ciclesonide in Treating Patients With Asymptomatic or Mild COVID-19 in the RACCO Trial: Protocol for a Multicenter, Open-label, Randomized Controlled Trial

Abstract

Background Currently, there are no specific effective treatments for SARS-CoV-2 infection; however, various COVID-19 treatment options are under investigation. It is vital to continue investigating the landscape of SARS-CoV-2–induced pneumonia and therapeutic interventions. Objective This paper presents the protocol for a randomized controlled trial that aims to compare the pneumonia exacerbation rate between ciclesonide (ALVESCO; Teijin Pharma Limited) administration and symptomatic treatment in patients with COVID-19 and to determine the efficacy of ciclesonide. The secondary objectives are to investigate the safety of ciclesonide administration, changes in clinical and laboratory findings, and the number of viral genome copies of SARS-CoV-2 over time between the 2 groups. Methods In this investigator-initiated, exploratory, prospective, multicenter, parallel-group, open-label, randomized controlled trial, a total of 90 patients diagnosed with COVID-19 will be recruited from 21 hospitals in Japan based on specific inclusion and exclusion criteria. Participants will be randomized either to the ciclesonide group, which will receive a 400-µg dose of ciclesonide 3 times per day over a 7-day period, or to the symptomatic treatment group. Both groups will receive antitussives and antipyretics as required. Data collection for various parameters will be conducted on days 1, 2, 4, 8, 22, and 29 to record baseline assessments and the findings over an extended period. Computed tomography images taken prior to drug administration and 1 week following treatment will be compared, and efficacy will be confirmed by checking for pneumonia exacerbation. Primary endpoint analysis will be performed using the Fisher exact test to determine statistically significant differences in the pneumonia exacerbation rate between the ciclesonide and symptomatic treatment groups. Results The first trial participant was enrolled on April 3, 2020. Recruitment is expected to be completed on September 30, 2020, while follow-up assessments of all participants are expected to be completed by October 31, 2020. The study results will be published in a peer-reviewed scientific journal. Conclusions The RACCO (Randomized Ciclesonid COVID-19) study will provide definitive comparative effectiveness data and important clinical outcomes data between the ciclesonide and symptomatic treatment groups. If the hypotheses that pneumonia exacerbation rate reduction is more significant in the ciclesonide treatment group than in the symptomatic treatment group and that ciclesonide is safe for use are valid, ciclesonide will serve as an important therapeutic option for patients with COVID-19. Trial Registration Japan Registry of Clinical Trials jRCTs031190269; https://jrct.niph.go.jp/en-latest-detail/jRCTs031190269 International Registered Report Identifier (IRRID) DERR1-10.2196/23830

COVID-19 and bronchial asthma: current perspectives

“…Regarding ICS, the Japanese Society of Infectious Diseases is leading the observational study of the administration of ciclesonide that has been found to have an antiviral effect on SARS-CoV-2. At the same time, a multicenter, open-label, randomized trial, led by the National Center for Global Health and Medicine, is underway to investigate its efficacy and safety in treating asymptomatic and mildly ill COVID-19 in patients (36).…”

COVID-19 and corticosteroids: a narrative review

“…It was demonstrated that ciclesonide exhibited positive outcomes towards COVID-19 (Deokar et al 2021 ). Previously ciclesonide was shown to inhibit the MERS virus and inhibited the lung inflammatory process (Terada-Hirashima et al 2020 ). Previous reports suggested that the virus penetrated alveolar cells, provoking lung injury and concurrently contaminated macrophages.…”

“…It has been shown that ciclesonide, an inhaled steroid drug, is associated with suppressed asthmatic attacks by reducing airway hyper-activity along with lung resistance following exposure to antigens (Terada-Hirashima et al 2020 ). Moreover, it was reported that ciclesonide suppressed the release of inflammatory mediators, slowed down the penetration of immune cells into the lung (Terada-Hirashima et al 2020 ). After inhalation, ciclesonide bound to its receptor thereafter exerted effective activities towards inflammation.…”

Favipiravir, camostat, and ciclesonide combination therapy in patients with moderate COVID-19 pneumonia with/without oxygen therapy: An open-label, single-center phase 3 randomized clinical trial

“…7 Ciclesonide is an inhaled corticosteroid that was previously shown to reduce local inflammation in the lungs and inhibit antiviral activity against SARS-CoV-2 in in vitro studies and clinical trials are being conducted to demonstrate the efficacy in mild COVID-19. 8 , 9 A recently phase 2 trial has shown that ciclesonide inhalation shortened SARS-CoV-2 viral shedding duration, and can potentially inhibit disease progression. 10 Camostat mesylate is a well-known oral serine protease inhibitor of the human transmembrane surface protease TMPRSS2, and it is a potential antiviral drug against COVID-19.…”