Intravenous methylprednisolone pulse as a treatment for hospitalised severe COVID-19 patients: results from a randomised controlled clinical trial

Abstract

Introduction: There are no determined treatment agents for severe COVID-19. It is suggested that methylprednisolone, as an immunosuppressive treatment, can reduce the inflammation of the respiratory system in COVID-19 patients.

Methods: We conducted a single-blind, randomised controlled clinical trial involving severe hospitalised patients with confirmed COVID-19 at the early pulmonary phase of the illness in Iran. The patients were randomly allocated in a 1:1 ratio by the block randomisation method to receive standard care with methylprednisolone pulse (intravenous injection, 250 mg·day^-1 for 3 days) or standard care alone. The study end-point was the time of clinical improvement or death, whichever came first. Primary and safety analysis was done in the intention-to-treat (ITT) population.

Results: 68 eligible patients underwent randomisation (34 patients in each group) from April 20, 2020 to June 20, 2020. In the standard care group, six patients received corticosteroids by the attending physician before the treatment and were excluded from the overall analysis. The percentage of improved patients was higher in the methylprednisolone group than in the standard care group (94.1% versus 57.1%) and the mortality rate was significantly lower in the methylprednisolone group (5.9% versus 42.9%; p<0.001). We demonstrated that patients in the methylprednisolone group had a significantly increased survival time compared with patients in the standard care group (log-rank test: p<0.001; hazard ratio 0.293, 95% CI 0.154-0.556). Two patients (5.8%) in the methylprednisolone group and two patients (7.1%) in the standard care group showed severe adverse events between initiation of treatment and the end of the study.

Conclusions: Our results suggest that methylprednisolone pulse could be an efficient therapeutic agent for hospitalised severe COVID-19 patients at the pulmonary phase.

FIGURE 1

Appropriate time for methylprednisolone administration and inclusion/exclusion criteria of the patients. Patients in the intervention group received methylprednisolone pulse (intravenous injection, 250 mg·day⁻¹ for 3 days) at the early pulmonary phase of the disease before connection to the ventilator and intubation. ICU: intensive care unit; S_pO2: arterial oxygen saturation measured by pulse oximetry; CRP: C-reactive protein; IL: interleukin; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; PCT: pro-calcitonin; ARDS: acute respiratory distress syndrome; GI: gastrointestinal.

FIGURE 2

Randomisation, enrolment and treatment assignment.

FIGURE 3

Kaplan–Meier estimator of survival rate between the methylprednisolone and standard care groups. Log-rank test: p<0.001; hazard ratio 0.293 (95% CI 0.154–0.556).