Discussion
cough, illness, reduced clinical deterioration
EVENTS, DISEASE
In this randomised placebo-controlled trial, hospitalised patients who received low dose spironolactone and dexamethasone in addition to standard of care had significantly lower D-dimer levels at days 4 and 7, and a lower aldosterone level at day 7 in comparison with those on dexamethasone alone with standard care. We did not observe a significant reduction in the time to recovery to WHO OS ≤ 3 but did observe a significant increase in oxygen free days in the SpiroDex group, as well as a trend towards a shorter time to oxygen freedom and a significant reduction in day and night cough scores for SpiroDex patients at day 28.Post hoc analysis demonstrated reduced clinical deterioration within the SpiroDex arm, and a reduced length of in-patient stay for those patients in the trial who were discharged from the Lok Nayak facility. In addition, treatment at this dose was safe with no recorded SAEs. This is the first report in a RCT setting of the potentially beneficial and safe addition of spironolactone to standard of care in COVID-19.We note several limitations to this trial. There was a higher proportion of male patients in the Dex than the SpiroDex group and it is known that males are at a higher risk of severe illness in COVID-19 [As the trial protocol did not allow for further data collection of patients after they deteriorated beyond WHO OS 4, the final outcomes for these individuals are unknown. In addition, a small number of patients had to be withdrawn from the trial due to their decision to be transferred to a different facility. In total, 12.2% of patients within the SpiroDex group withdrew from the trial versus 15.2% from the Dex group.A raised D-dimer is associated with increased mortality in COVID-19 disease, and it is a recognised prognostic indicator of adverse outcomes [Loss of the specificity of the MR results in a key sequence of events. MR activation releases ATP which then acts on purinergic receptors on the cell and adjacent cells to increase intracellular calcium [It is anticipated that SARS-CoV-2 will remain endemic within the global population even with a successful vaccination program. Together with the potential of variants of the SARS-CoV-2 emerging, new affordable and widely available treatments are needed. The promising safety biomarker (D-dimer) and clinical outcomes demonstrated in this phase 2 RCT support the evaluation of spironolactone together with dexamethasone in COVID-19 in larger randomised phase 3 controlled trials.