High dose dexamethasone reduced clinical worsening within 11 days more effectively than low dose dexamethasone in patients hospitalized with COVID-19 pneumonia requiring oxygen therapy, according to clinical trial findings recently published in the European Respiratory Journal.
Research findings came from the HIGHLOWDEXA trial (ClinicalTrials.gov Identifier: NCT04726098), a randomized, controlled clinical trial to evaluate the efficacy of high dose dexamethasone (20 mg once daily for 5 days, followed by 10 mg once daily for 5 days) vs low dose dexamethasone (6 mg once daily for 10 days) in patients hospitalized with COVID-19 pneumonia requiring oxygen therapy. This open-label study included 200 adult patients (mean (SD) age, 64 (14) years; 62% male), with 102 patients receiving low-dose dexamethasone and 98 receiving high-dose. The researchers hypothesized that high dose dexamethasone might reduce the risk of clinical worsening (defined as the need to increase fraction of inspired oxygen >0.2, the need for fraction of inspired oxygen >0.5, and/or respiratory rate >25) or a score higher than 4 on the 7-point ordinal scale WHO-CIS (World Health Organization clinical improvement score). Notably, for ethical reasons, patients in the low dose group who suffered clinical worsening were allowed to receive high dose of dexamethasone.
Investigators’ chief finding was that 31.4% of patients in the low dose group and 16.3% of those in the high dose group exhibited clinical worsening within 11 days of randomization (rate ratio, 0.427; 95% CI, 0.216-0.842; P =.014).
The 28-day mortality was 5.9% in the low dose group and 6.1% in the high dose group (P =.844), and there was no significant difference between the 2 groups in time to recovery or in the 7-point ordinal scale at day 5, 11, 14 and 28. According to the investigators, “This may be explained mainly because in the low dose group, all patients who suffered a clinical worsening, high dose of dexamethasone was administered.” Many of these patients improved after receiving high dose dexamethasone. The decision to allow a rescue therapy with high dose dexamethasone, motivated by ethical concerns, biased these secondary endpoint results and thus represented a limitation of the trial findings.
Researchers concluded that, “Among hospitalized COVID-19 patients needing oxygen therapy, high dose of dexamethasone reduced clinical worsening within 11 days after randomization as compared with low dose.” The added that high dose dexamethasone was not associated with an increased risk of adverse events in this patient population.
Taboada M, Rodríguez N, Varela PM, et al. Effect of high versus low dose of dexamethasone on clinical worsening in patients hospitalised with moderate or severe COVID-19 Pneumonia: an open-label, randomised clinical trial. Eur Respir J. Published online Decembter 16, 2021. doi:10.1183/13993003.02518-2021