COVIDORL (NCT04361474).

Study name	Trial evaluating the efficacy of local budesonide therapy in the management of hyposmia in COVID‐19 patients without signs of severity (COVIDORL)
Methods	Parallel‐group randomised controlled trial
Participants	Individuals with persistent hyposmia at 30 days following the onset of SARS‐CoV‐2 infection Inclusion criteria for the study: Patients over 18 years of age Patient with a suspected SARS‐CoV‐2 infection (whether or not confirmed by PCR), or contact close to a PCR‐confirmed case, typical chest CT scan (unsystematised frosted glass areas predominantly sub‐pleural, and at a later stage of alveolar condensation with no excavations neither nodules nor masses) or positive serology Isolated acute hyposmia persisting at 30 days after SARS‐CoV‐2 symptom onset Absence of PCR‐confirmed SARS‐CoV‐2 carriage at the time of inclusion Exclusion criteria for the study: Hypersensitivity to budesonide or any excipients of the medicine Haemostasis disorder, or epistaxis Oral/nasal/ophthalmic herpes virus infection Long‐term corticosteroid infection Treatment with CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin, nefazodone or HIV proteases) Respiratory signs or other symptoms of SARS‐CoV‐2 persisting at day 30 from the onset of infection Hyposmia persisting for more than 90 days after onset of symptoms Other causes of hyposmia revealed on interrogation or MRI Planned sample size: estimated enrolment 120 participants
Interventions	Intervention: nasal irrigation with budesonide and physiological saline (budesonide 1 mg/2 mL diluted in 250 mL of physiological saline: 3 syringes of 20 mL in each nasal cavity, morning and evening, for 30 days Comparator: nasal irrigation with physiological saline only: 3 syringes of 20 mL in each nasal cavity, morning and evening, for 30 days Additional intervention to be used in both groups: olfactory training twice a day
Outcomes	Outcomes of interest in the review Primary outcomes: Recovery of sense of smell Self‐reported by the participants, as a response to the question "Have you fully recovered the olfactory capacities that you had before the onset of the symptoms of COVID‐19?" Disease‐related quality of life Not reported Serious adverse effects Protocol states "evaluate the tolerance of budesonide" with a description of serious adverse events Secondary outcomes: Change in sense of smell Percentage of patients who show an improvement in sense of smell of more than 2 points on the ODORATEST score. From the protocol: ODORATEST overall score, and detection and identification subscores at 30 days. Measured after 30 days of treatment Overall, generic quality of life Not reported Prevalence of parosmia Not reported Other adverse effects (including nosebleeds/bloody discharge) Protocol states "evaluate the tolerance of budesonide" with a description of serious adverse events Other outcomes reported by the study: Olfactory and gustatory capacities of the patients using a self‐assessment questionnaire Presence of inflammatory filling of the olfactory cleft on MRI or the presence of neurological damage to the olfactory bulb
Starting date	18 May 2020
Contact information	Mary Daval Email: mdaval@for.paris
Notes	Estimated study completion date: 25 May 2021 Trial registered in France. A further extension study is planned for those who have not fully recovered by day 30, including additional budesonide for 30 days for those in the intervention arm, and starting budesonide for those in the placebo arm.