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

Abstract

Background: Low-dose dexamethasone demonstrated clinical improvement in patients with coronavirus disease 2019 (COVID-19) needing oxygen therapy; however, evidence on the efficacy of high-dose dexamethasone is limited.

Methods: We performed a randomised, open-label, controlled trial involving hospitalised patients with confirmed COVID-19 pneumonia needing oxygen therapy. Patients were randomly assigned in a 1:1 ratio to receive low-dose dexamethasone (6 mg once daily for 10 days) or high-dose dexamethasone (20 mg once daily for 5 days, followed by 10 mg once daily for an additional 5 days). The primary outcome was clinical worsening within 11 days since randomisation. Secondary outcomes included 28-day mortality, time to recovery and clinical status at day 5, 11, 14 and 28 on an ordinal scale ranging from 1 (discharged) to 7 (death).

Results: A total of 200 patients (mean±sd age 64±14 years; 62% male) were enrolled. 32 (31.4%) out of 102 patients enrolled in the low-dose group and 16 (16.3%) out of 98 in the high-dose group showed clinical worsening within 11 days since randomisation (rate ratio 0.427, 95% CI 0.216-0.842; p=0.014). The 28-day mortality was 5.9% in the low-dose group and 6.1% in the high-dose group (p=0.844). There was no significant difference in time to recovery, and in the seven-point ordinal scale at days 5, 11, 14 and 28.

Conclusions: Among hospitalised COVID-19 patients needing oxygen therapy, high dose of dexamethasone reduced clinical worsening within 11 days after randomisation, compared with low dose.

Trial registration: ClinicalTrials.gov NCT04726098.

FIGURE 1

Screening, randomisation and outcomes. F_iO2: inspiratory oxygen fraction; S_pO2: peripheral oxygen saturation; ICU: intensive care unit.

FIGURE 2

Kaplan–Meier analysis of efficacy outcomes: Kaplan–Meier curves for the time-to-event analyses of a) clinical worsening (primary outcome); b) recovery, defined as the first day after enrolment on which a patient attained category 1, 2 or 3 on the seven-point ordinal scale (scores range from 1 to 7, with higher scores indicating worse clinical condition); c) hospital discharge; d) death.

FIGURE 3

Clinical status on a seven-point ordinal scale on study days 5, 11, 14 and 28 by treatment group. All percentage values in each point category are provided in supplementary table S3. At day 5, p=0.885 for comparison of the distribution of the high-dose group versus low-dose group. At day 11, p=0.666 for comparison of the distribution of the high-dose group versus low-dose group. At day 14, p=0.870 for comparison of the distribution of the high-dose group versus low-dose group. At day 28, p=0.831 for comparison of the distribution of the high-dose group versus low-dose group.