ABSTRACT
OBJECTIVE: To determine if inhaled and intranasal ciclesonide are superior to placebo at decreasing respiratory symptoms in adult outpatients with covid-19. DESIGN: Randomised, double blind, placebo controlled trial. SETTING: Three Canadian provinces (Quebec, Ontario, and British Columbia). PARTICIPANTS: 203 adults aged 18 years and older with polymerase chain reaction confirmed covid-19, presenting with fever, cough, or dyspnoea. INTERVENTION: Participants were randomised to receive either inhaled ciclesonide (600 µg twice daily) and intranasal ciclesonide (200 µg daily) or metered dose inhaler and nasal saline placebos for 14 days. MAIN OUTCOME MEASURES: The primary outcome was symptom resolution at day 7. Analyses were conducted on the modified intention-to-treat population (participants who took at least one dose of study drug and completed one follow-up survey) and adjusted for stratified randomisation by sex. RESULTS: The modified intention-to-treat population included 203 participants: 105 were randomly assigned to ciclesonide (excluding two dropouts and one loss to follow-up) and 98 to placebo (excluding three dropouts and six losses to follow-up). The median age was 35 years (interquartile range 27-47 years) and 54% were women. The proportion of participants with resolution of symptoms by day 7 did not differ significantly between the intervention group (42/105, 40%) and control group (34/98, 35%); absolute adjusted risk difference 5.5% (95% confidence interval -7.8% to 18.8%). Results might be limited to the population studied, which mainly included younger adults without comorbidities. The trial was stopped early, therefore could have been underpowered. CONCLUSION: Compared with placebo, the combination of inhaled and intranasal ciclesonide did not show a statistically significant increase in resolution of symptoms among healthier young adults with covid-19 presenting with prominent respiratory symptoms. As evidence is insufficient to determine the benefit of inhaled and intranasal corticosteroids in the treatment of covid-19, further research is needed. TRIAL REGISTRATION: ClinicalTrials.gov NCT04435795.
Subject(s)
Adrenal Cortex Hormones/administration & dosage , Ambulatory Care/methods , COVID-19 Drug Treatment , Pregnenediones/administration & dosage , Administration, Inhalation , Adolescent , Adrenal Cortex Hormones/therapeutic use , Adult , Aged , Aged, 80 and over , Double-Blind Method , Drug Administration Schedule , Female , Follow-Up Studies , Humans , Intention to Treat Analysis , Male , Middle Aged , Pregnenediones/therapeutic use , Self Report , Treatment Outcome , Young AdultABSTRACT
We provide the details of the successful management of a patient with active Cushing's disease complicated with coronavirus disease 2019 (COVID-19) pneumonia. The patient was a 27-year-old Japanese female healthcare worker who was scheduled to undergo pituitary surgery for Cushing's disease. She had been in close contact with an undiagnosed patient infected with COVID-19 and then developed COVID-19 pneumonia. Despite a lack of known risk factors associated with severe COVID-19 infection, the patient's dyspnea worsened and her respiratory condition deteriorated, as indicated by the need for 7 L/min oxygen supply by mask to maintain her oxygen saturation at >90%. Medical treatment was initiated to control hypercortisolism by the 'block and replace' regimen using steroidogenesis inhibitors and hydrocortisone. The COVID-19 pneumonia improved with multi-modal treatment including antiviral therapy. One month later, after a negative severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) test result and with appropriate protection against virus transmission to medical staff in the operating room and daily medical care nurses, trans-sphenoidal surgery was performed by our highly experienced pituitary surgeon. One month after the surgery, the patient's basal ACTH and cortisol levels and urinary free cortisol were all under the detection limit. Surgical remission was expected. Since hypercortisolism due to active Cushing's disease may worsen a COVID-19 infection, multi-disciplinary management that includes appropriate and prompt treatment strategies is mandatory in such cases.
Subject(s)
Amides/administration & dosage , Benzamidines/administration & dosage , COVID-19/therapy , Guanidines/administration & dosage , Metyrapone/administration & dosage , Pituitary ACTH Hypersecretion/therapy , Pregnenediones/administration & dosage , Pyrazines/administration & dosage , ACTH-Secreting Pituitary Adenoma/complications , ACTH-Secreting Pituitary Adenoma/drug therapy , Adenoma/complications , Adenoma/drug therapy , Adult , COVID-19/complications , COVID-19/pathology , Combined Modality Therapy , Dihydrotestosterone/administration & dosage , Dihydrotestosterone/analogs & derivatives , Disease Progression , Female , Health Personnel , Heparin/administration & dosage , Humans , Japan , Neurosurgical Procedures , Pituitary ACTH Hypersecretion/blood , Pituitary ACTH Hypersecretion/complications , Pituitary ACTH Hypersecretion/pathology , SARS-CoV-2/physiology , Treatment Outcome , Trimethoprim, Sulfamethoxazole Drug Combination/administration & dosageABSTRACT
Achieving appropriate inhalation in patients with coronavirus disease 2019 (COVID-19) is a common challenge in the use of repurposed metered-dose inhaler (MDI) formulations. The purpose of this study was to evaluate the effect of five valved holding chambers (VHCs) on the inhalation of ciclesonide from Alvesco MDI. The aerodynamic particle size distribution of ciclesonide discharged from Alvesco MDI was evaluated using a Next Generation Impactor in the presence and absence of VHCs. The use of VHCs retained or slightly increased the amount of ciclesonide in the fine particle diameter range (aerodynamic particle size below 3 µm) (FPD) and reduced the amount at the induction port after coordinated inhalation. However, the use of VHC reduced the FPD of the formulation by increasing the time between the MDI discharge and the pump suction by various degrees among the five VHCs. These results indicated that use of the VHCs and minimizing the inhalation delay time should ensure sufficient inhalation of ciclesonide particles.