Inhaled ciclesonide for outpatient treatment of COVID-19 in adults at risk of adverse outcomes: a randomised controlled trial (COVERAGE)

Duvignaud et al., Clinical Microbiology and Infection, doi:10.1016/j.cmi.2022.02.031, NCT04356495

Mar 2022

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Early terminated RCT with 110 ciclesonide patients and 107 patients treated with vitamins A, B1, B2, B3, B5, B6, B8, B9, B12, C, D3, and E, calcium, chromium, copper, iron, manganese, molybdenum, selenium, and zinc (Azinc Vitality), showing no significant differences between the two treatments. There was no control group. NCT04356495 (history). EudraCT 2020-001435-27.

Targeted administration to the respiratory tract provides treatment directly to the typical source of initial SARS-CoV-2 infection and replication, and allows for rapid onset of action, higher local drug concentration, and reduced systemic side effects.

This study is excluded in meta analysis: study compares against another treatment showing significant efficacy.

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risk of death, 80.2% lower, RR 0.20, p = 0.24, treatment 0 of 110 (0.0%), control 2 of 107 (1.9%), NNT 54, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), day 28.

risk of death, 67.0% lower, RR 0.33, p = 0.49, treatment 0 of 110 (0.0%), control 1 of 107 (0.9%), NNT 107, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), day 14.

risk of hospitalization, 36.2% higher, RR 1.36, p = 0.52, treatment 14 of 110 (12.7%), control 10 of 107 (9.3%), day 28.

risk of hospitalization, 29.7% higher, RR 1.30, p = 0.65, treatment 12 of 110 (10.9%), control 9 of 107 (8.4%), day 14.

risk of progression, 19.7% higher, RR 1.20, p = 0.69, treatment 16 of 110 (14.5%), control 13 of 107 (12.1%), oxygen, hospitalization, or death, day 28.

risk of progression, 13.5% higher, RR 1.13, p = 0.84, treatment 14 of 110 (12.7%), control 12 of 107 (11.2%), oxygen, hospitalization, or death, day 14, primary outcome.

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

Duvignaud et al., 16 Mar 2022, Randomized Controlled Trial, France, peer-reviewed, median age 63.0, 314 authors, study period 29 July, 2020 - 22 October, 2021, average treatment delay 4.0 days, this trial compares with another treatment - results may be better when compared to placebo, trial NCT04356495 (history).

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Inhaled ciclesonide for outpatient treatment of COVID-19 in adults at risk of adverse outcomes: a randomised controlled trial (COVERAGE)

Alexandre Duvignaud, Edouard Lhomme, Racha Onaisi, Rémi Sitta, Ambre Gelley, Julie Chastang, Lionel Piroth, Christine Binquet, Julie Dupouy, Alain Makinson, Benjamin Lefèvre, Jean-Marc Naccache, Caroline Roussillon, Roland Landman, Cédrick Wallet, Sophie Karcher, Valérie Journot, Duc Nguyen, Thierry Pistone, Stéphane Bouchet, Marie-Edith Lafon, Mathieu Molimard, Rodolphe Thiébaut, Xavier De Lamballerie, Jean-Philippe Joseph, Laura Richert, Olivier Saint-Lary, Sarah Djabarouti, Linda Wittkop, Xavier Anglaret, Denis Malvy

Clinical Microbiology and Infection, doi:10.1016/j.cmi.2022.02.031

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Author contribution statement Alexandre Duvignaud (AD), Edouard Lhomme (EL), Racha Onaisi, Rémi Sitta (RS), Duc Nguyen (DN), Thierry Pistone (TP), Rodolphe Thiébaut, Jean-Philippe Joseph, Laura Richert (LR), Linda Confit of interest All authors declare no conflict of interest. Trial registration The trial protocol was registered in the European database EudraCT (2020-001435-27) and on clinicaltrials.gov (NCT04356495). J o u r n a l P r e -p r o o f Role of funding source The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. J o u r n a l P r e -p r o o f LIST OF FIGURES Figure 1. CONSORT Flow Diagram Footnotes to Figure 1 This figure shows the flow of participants through Day 14. The number of participants included in the analyses covering the 28-day follow-up is shown in Tables 2 and 3 . ITT=intention-to-treat; mITT=modified intention-to-treat; PP=per protocol; (1) Participant on chronic inhaled corticosteroid therapy (exclusion criteria) (2) Participants who have not been lost to follow-up before Day-9 and have not completed the 10-day treatment for reasons other than the occurrence of an adverse event. (3) Patients lost to follow-up were excluded from the ITT analysis (4) Reasons: lost to follow-up, n=2 ; major of eligibility criteria, n=2 (untreated diabetes, n=1; patient requiring oxygen therapy before randomisation, n=1) (5) Reasons: lost to follow-up, n=4 ; major violation..

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