The RACCO Trial to Assess the Efficacy and Safety of Inhaled Ciclesonide for Asymptomatic and Mild Patients with Covid-19: A Study Protocol for a Multi-center, Open- labeled, Randomized Controlled Trial (Preprint)

BACKGROUND Currently, there are no specific effective treatments for SARS-CoV-2; 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 study that aims to compare the pneumonia exacerbation rate between ciclesonide (Alvesco R) administration and symptomatic treatment in COVID-19 patients and to determine the efficacy of ciclesonide (Alvesco R). The secondary objectives are to investigate the safety of ciclesonide (Alvesco R) administration, changes in clinical and laboratory findings, and the number of viral genome copies of SARS-CoV-2 over time between the two groups. METHODS In this investigator-initiated, exploratory, prospective, multi-center, parallel-group, open-label, randomized trial, a total of 90 patients diagnosed with COVID-19 with specific inclusion/exclusion criteria will be recruited from 21 hospitals in Japan. Participants will be randomized to either the ciclesonide group receiving ciclesonide (Alvesco R) 400 µg dose three times a day over a seven-day period or to the symptomatic treatment group. Both groups will 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 (CT) image scans 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 Fisher's 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 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 (Alvesco R) will serve as an important therapeutic option for COVID-19 patients. CLINICALTRIAL Japan Registry of Clinical Trials NCT No jRCTs031190269. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/23830.