Phase 2 randomised placebo-controlled trial of spironolactone and dexamethasone versus dexamethasone in COVID-19 hospitalised patients in Delhi.

Autor: Wadhwa B; Department of Anaesthesia, Maulana Azad Medical College, New Delhi, India. drbhartitaneja@gmail.com., Malhotra V; Department of ENT & Head and Neck Surgery, Maulana Azad Medical College & Associated Hospitals, New Delhi, India., Kerai S; Department of Anaesthesia, Maulana Azad Medical College, New Delhi, India., Husain F; Department of Anaesthesia, Maulana Azad Medical College, New Delhi, India., Pandey NB; Department of Anaesthesia, Maulana Azad Medical College, New Delhi, India., Saxena KN; Department of Anaesthesia, Maulana Azad Medical College, New Delhi, India., Singh V; Department of Anaesthesia, Maulana Azad Medical College, New Delhi, India., Quinn TM; Centre for Inflammation Research, The Queen's Medical Research Institute, BioQuarter, The University of Edinburgh, Edinburgh, EH16 4TJ, UK.; Royal Infirmary of Edinburgh, BioQuarter, Little France, Edinburgh, EH16 4SA, UK., Li F; Centre for Inflammation Research, The Queen's Medical Research Institute, BioQuarter, The University of Edinburgh, Edinburgh, EH16 4TJ, UK., Gaughan E; Centre for Inflammation Research, The Queen's Medical Research Institute, BioQuarter, The University of Edinburgh, Edinburgh, EH16 4TJ, UK.; Royal Infirmary of Edinburgh, BioQuarter, Little France, Edinburgh, EH16 4SA, UK., Shankar-Hari M; Centre for Inflammation Research, The Queen's Medical Research Institute, BioQuarter, The University of Edinburgh, Edinburgh, EH16 4TJ, UK.; Royal Infirmary of Edinburgh, BioQuarter, Little France, Edinburgh, EH16 4SA, UK., Mills B; Centre for Inflammation Research, The Queen's Medical Research Institute, BioQuarter, The University of Edinburgh, Edinburgh, EH16 4TJ, UK., Antonelli J; Centre for Inflammation Research, The Queen's Medical Research Institute, BioQuarter, The University of Edinburgh, Edinburgh, EH16 4TJ, UK., Bruce A; Centre for Inflammation Research, The Queen's Medical Research Institute, BioQuarter, The University of Edinburgh, Edinburgh, EH16 4TJ, UK., Finlayson K; Centre for Inflammation Research, The Queen's Medical Research Institute, BioQuarter, The University of Edinburgh, Edinburgh, EH16 4TJ, UK., Moore A; Centre for Inflammation Research, The Queen's Medical Research Institute, BioQuarter, The University of Edinburgh, Edinburgh, EH16 4TJ, UK., Dhaliwal K; Centre for Inflammation Research, The Queen's Medical Research Institute, BioQuarter, The University of Edinburgh, Edinburgh, EH16 4TJ, UK. Kev.Dhaliwal@ed.ac.uk.; Royal Infirmary of Edinburgh, BioQuarter, Little France, Edinburgh, EH16 4SA, UK. Kev.Dhaliwal@ed.ac.uk., Edwards C; Imperial College, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK. c.edwards@newcastle.ac.uk.
Jazyk: angličtina
Zdroj: BMC infectious diseases [BMC Infect Dis] 2023 May 15; Vol. 23 (1), pp. 326. Date of Electronic Publication: 2023 May 15.
DOI: 10.1186/s12879-023-08286-w
Abstrakt: Background: In this phase 2 randomised placebo-controlled clinical trial in patients with COVID-19, we hypothesised that blocking mineralocorticoid receptors using a combination of dexamethasone to suppress cortisol secretion and spironolactone is safe and may reduce illness severity.
Methods: Hospitalised patients with confirmed COVID-19 were randomly allocated to low dose oral spironolactone (50 mg day 1, then 25 mg once daily for 21 days) or standard of care in a 2:1 ratio. Both groups received dexamethasone 6 mg daily for 10 days. Group allocation was blinded to the patient and research team. Primary outcomes were time to recovery, defined as the number of days until patients achieved WHO Ordinal Scale (OS) category ≤ 3, and the effect of spironolactone on aldosterone, D-dimer, angiotensin II and Von Willebrand Factor (VWF).
Results: One hundred twenty patients with PCR confirmed COVID were recruited in Delhi from 01 February to 30 April 2021. 74 were randomly assigned to spironolactone and dexamethasone (SpiroDex), and 46 to dexamethasone alone (Dex). There was no significant difference in the time to recovery between SpiroDex and Dex groups (SpiroDex median 4.5 days, Dex median 5.5 days, p = 0.055). SpiroDex patients had significantly lower D-dimer levels on days 4 and 7 (day 7 mean D-dimer: SpiroDex 1.15 µg/mL, Dex 3.15 µg/mL, p = 0.0004) and aldosterone at day 7 (SpiroDex 6.8 ng/dL, Dex 14.52 ng/dL, p = 0.0075). There was no difference in VWF or angiotensin II levels between groups. For secondary outcomes, SpiroDex patients had a significantly greater number of oxygen free days and reached oxygen freedom sooner than the Dex group. Cough scores were no different during the acute illness, however the SpiroDex group had lower scores at day 28. There was no difference in corticosteroid levels between groups. There was no increase in adverse events in patients receiving SpiroDex.
Conclusion: Low dose oral spironolactone in addition to dexamethasone was safe and reduced D-dimer and aldosterone. Time to recovery was not significantly reduced. Phase 3 randomised controlled trials with spironolactone and dexamethasone should be considered.
Trial Registration: The trial was registered on the Clinical Trials Registry of India TRI: CTRI/2021/03/031721, reference: REF/2021/03/041472. Registered on 04/03/2021.
(© 2023. The Author(s).)
Databáze: MEDLINE
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