Phase 2 randomised placebo-controlled trial of spironolactone and dexamethasone versus dexamethasone in COVID-19 hospitalised patients in Delhi
RCT 120 hospitalized patients in India, 74 treated with spironolactone and dexamethasone, and 46 with dexamethasone, showing lower progression with treatment. Spironolactone 50mg once daily day 1, 25mg once daily until day 21.
risk of progression, 72.4% lower, RR 0.28, p = 0.03, treatment 4 of 74 (5.4%), control 9 of 46 (19.6%), NNT 7.1, progression to WHO >4.
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risk of no hospital discharge, 49.5% lower, RR 0.51, p = 0.048, treatment 13 of 74 (17.6%), control 16 of 46 (34.8%), NNT 5.8.
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recovery time, 18.2% lower, relative time 0.82, p = 0.06, treatment 74, control 46.
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Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
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Wadhwa et al., 2 Jul 2022, Randomized Controlled Trial, placebo-controlled, India, preprint, 18 authors, study period 1 February, 2021 - 30 April, 2021, trial
CTRI/2021/03/031721.
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(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.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..
Late treatment
is less effective
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