An early short-course oral regimen combining prednisolone, colchicine, salicylate, direct anti-Xa inhibitor and furosemide may reduce the risk of high flow oxygen need, mechanical ventilation requirement or 28-day mortality in hospitalised non-critically ill coronavirus disease 2019 (COVID-19) patients, according to a study published in the Journal of Infection.
“Based on the data [from previous studies] and the pathophysiology of COVID-19 and its complications, i.e. thrombosis, inflammation and congestion, we hypothesised that a five-drug regimen consisting in a 5-day course of 1mg/kg/day prednisone, 80 mg/day furosemide, 75 mg/day salicylate, colchicine (1mg loading dose followed by 0.5 mg one hour later then 0.5 mg every 8h as recommended to treat acute gout) and direct anti-Xa inhibitor such as rivaroxaban or apixaban would optimally mitigate COVID-19-attributed mortality,” wrote Jean-Philippe Kevorkian, Université de Paris, Paris, France and colleagues.
A total of 68 non-critically ill COVID-19 patients (median age, 66 years) requiring >1L/min-oxygen admitted between January 9 and November 30, 2020 were included in this observational study. Of the patients, 28 (41%) received the five drug-therapy regimen while 40 (59%) in the control group were treated with dexamethasone (6 mg once daily for up to 10 days). The primary composite endpoint was the requirement of high-flow oxygen therapy, non-invasive or invasive mechanical ventilation (corresponding to care escalation from ward to intensive care unit [ICU]) or 28-day mortality).
Among patients receiving the five-drug regimen, study data showed that the incidence of primary composite endpoint was lower than that in the control group (odds ratio [OR], 0.097; 95% confidence interval [CI], 0.001-0.48; P = 0.0009). Multivariate analysis confirmed the significant effect of the five-drug regimen on outcome after adjusting for covariates including age, body-mass index, 4C Mortality Score, high serum brain natriuretic peptide (BNP) level and high white blood cell count (OR, 0.043; 95% CI, 0.0053-0.21; P = 0.0005).
Additionally, the researchers analysed patient subgroups following stratification by age, gender and risk factors including diabetes, elevated BNP (threshold, 100ng/ml) and troponin levels (threshold, 16ng/mL). They found that the five-drug regimen was associated with a significant reduction in primary composite endpoint in males only (OR, 0.059; 95% CI, 0.01-0.45; P = 0.0009). Further, the primary composite endpoint was improved in patients with elevated-BNP compared with low-BNP patients (P = 0.0003).
“The five drugs included in our regimen were given orally for a short course, paving the way for an outpatient treatment,” the authors noted. Nonetheless, they said that these preliminary observational findings should be confirmed in larger cohorts.