Abstract: medRxiv preprint doi: https://doi.org/10.1101/2022.07.01.22277163; this version posted July 2, 2022. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . TITLE: Phase 2 randomised placebo-controlled trial of spironolactone and dexamethasone versus dexamethasone in COVID-19 hospitalised patients in Delhi Bharti Wadhwa1*, Vikas Malhotra2, Sukhyanti Kerai1, Farah Husain1, Nalini Bala Pandey1, Kirti N Saxena1, Vinay Singh1, Tom M Quinn3,4*, Feng Li3, Erin Gaughan3,4, Manu ShankarHari3, Bethany Mills3, Jean Antonelli3, Annya Bruce3, Keith Finlayson3, Anne Moore3, Kevin Dhaliwal3,4*, Christopher Edwards5* *Corresponding authors Affiliations 1 Department of Anaesthesia, Maulana Azad Medical College, New Delhi, India 2 Department of ENT & Head and Neck Surgery, Maulana Azad Medical College & Associated Hospitals, New Delhi, India 3 Centre for Inflammation Research, The Queen’s Medical Research Institute, BioQuarter, The University of Edinburgh, Edinburgh, EH16 4TJ, UK 4 Royal Infirmary of Edinburgh, BioQuarter, Little France, Edinburgh, EH16 4SA, UK 5 Imperial College, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK 1 NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2022.07.01.22277163; this version posted July 2, 2022. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . ABSTRACT Background: In this phase 2 randomised placebo-controlled clinical trial, we hypothesised that blocking mineralocorticoid receptors with spironolactone in patients with COVID-19 is safe and may reduce illness severity. Methods: Hospitalised patients with confirmed COVID-19 were randomly allocated to low dose oral spironolactone (50mg day 1, then 25mg once daily for 21 days) or standard care in a 2:1 ratio. Both groups received dexamethasone 6mg 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: 120 patients 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 lower aldosterone levels on day 7 and lower D-dimer levels on days 4 and 7 (day 7 D-dimer mean SpiroDex 1.15μg/mL, Dex 3.15 μg/mL, p = 0.0004). There was no increase in adverse events in patients receiving SpiroDex. Post hoc analysis demonstrated reduced clinical deterioration (pre specified as escalating to WHO OS category >4) in the SpiroDex group vs Dex group (5.4% vs 19.6%). Conclusion: Low dose oral spironolactone in addition to dexamethasone was safe and reduced D-Dimer and aldosterone. Although time to recovery was not..