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

Alexandre Duvignaud (1, 2) , Edouard Lhomme (3, 1, 4, 2) , Racha Onaisi (5) , Rémi Sitta (2, 4) , Ambre Gelley (4) , Julie Chastang (6, 7) , Lionel Piroth (8, 9) , Christine Binquet (9) , Julie Dupouy (10, 11) , Alain Makinson (12, 13, 14) , Benjamin Lefèvre (15, 16) , Jean-Marc Naccache (17) , Caroline Roussillon (2) , Roland Landman (18, 19, 20) , Cédrick Wallet (4) , Sophie Karcher (1) , Valérie Journot (1) , Duc Nguyen (1, 2) , Thierry Pistone (1, 2) , Stéphane Bouchet (2) , Marie-Edith Lafon (21) , Mathieu Molimard (2) , Rodolphe Thiébaut (3, 1, 2, 4) , Xavier de Lamballerie (22) , Jean-Philippe Joseph (5) , Laura Richert (3, 1, 2, 4) , Olivier Saint-Lary (23, 24) , Sarah Djabarouti (2, 25) , Linda Wittkop (3, 1, 2, 4) , Xavier Anglaret (1) , Denis Malvy (1, 2)

1 BPH - Bordeaux population health
2 CHU Bordeaux
3 SISTM - Statistics In System biology and Translational Medicine
4 CIC Bordeaux
5 UB - Université de Bordeaux
6 iPLESP - Institut Pierre Louis d'Epidémiologie et de Santé Publique
7 Sorbonne Université - Département de médecine générale
8 CHU Dijon - Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand
9 CIC-EC - Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques
10 CERPOP - Centre d'Epidémiologie et de Recherche en santé des POPulations
11 UT3 - Université Toulouse III - Paul Sabatier
12 CIC Montpellier
13 Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France
14 TransVIHMI - Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes
15 APEMAC - Adaptation, mesure et évaluation en santé. Approches interdisciplinaires
16 Service des Maladies Infectieuses et Tropicales [CHRU Nancy]
17 hpsj - Groupe Hospitalier Paris Saint-Joseph
18 IAME (UMR_S_1137 / U1137) - Infection, Anti-microbiens, Modélisation, Evolution
19 IMEA - Institut de médecine et d'épidémiologie appliquée [AP-HP Hôpital Bichat-Claude Bernard]
20 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
21 MFP - Microbiologie Fondamentale et Pathogénicité
22 UVE - Unité des Virus Emergents
23 CESP - Centre de recherche en épidémiologie et santé des populations
24 UVSQ Santé - Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil
25 Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases

Objectives: To assess the efficacy of inhaled ciclesonide in reducing the risk of adverse outcomes in COVID-19 outpatients at risk of developing severe illness. Methods: COVERAGE is an open-label, randomized controlled trial. Outpatients with documented COVID-19, risk factors for aggravation, symptoms for ≤7 days, and absence of criteria for hospitalization are randomly allocated to either a control arm or one of several experimental arms, including inhaled ciclesonide. The primary efficacy endpoint is COVID-19 worsening (hospitalization, oxygen therapy at home, or death) by Day 14. Other endpoints are adverse events, maximal follow-up score on the WHO Ordinal Scale for Clinical Improvement, sustained alleviation of symptoms, cure, and RT-PCR and blood parameter evolution at Day 7. The trial's Safety Monitoring Board reviewed the first interim analysis of the ciclesonide arm and recommended halting it for futility. The results of this analysis are reported here. Results: The analysis involved 217 participants (control 107, ciclesonide 110), including 111 women and 106 men. Their median age was 63 years (interquartile range 59-68), and 157 of 217 (72.4%) had at least one comorbidity. The median time since first symptom was 4 days (interquartile range 3-5). During the 28-day follow-up, 2 participants died (control 2/107 [1.9%], ciclesonide 0), 4 received oxygen therapy at home and were not hospitalized (control 2/107 [1.9%], ciclesonide 2/110 [1.8%]), and 24 were hospitalized (control 10/107 [9.3%], ciclesonide 14/110 [12.7%]). In intent-to-treat analysis of observed data, 26 participants reached the composite primary endpoint by Day 14, including 12 of 106 (11.3%, 95% CI: 6.0%-18.9%) in the control arm and 14 of 106 (13.2%; 95% CI: 7.4-21.2%) in the ciclesonide arm. Secondary outcomes were similar for both arms. Discussion: Our findings are consistent with the European Medicines Agency's COVID-19 task force statement that there is currently insufficient evidence that inhaled corticosteroids are beneficial for patients with COVID-19.

Mots clés: Adults; COVID-19; Ciclesonide; Inhaled corticosteroids; Outpatients; Randomized controlled trial; Treatment

Domaines: Virologie; Médicaments; Santé publique et épidémiologie

Alexandre Duvignaud, Edouard Lhomme, Racha Onaisi, Rémi Sitta, Ambre Gelley, et al.. Inhaled ciclesonide for outpatient treatment of COVID-19 in adults at risk of adverse outcomes: a randomised controlled trial (COVERAGE). Clinical Microbiology and Infection, 2022, 28 (7), pp.1010-1016. ⟨10.1016/j.cmi.2022.02.031⟩. ⟨hal-03690132⟩