Efficacy, Safety, and Tolerability of Methylprednisolone in Critically Ill Patients With the Hyperinflammatory Phenotype: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase II Trial

Official Summary

The goal of this clinical trial is to learn whether methylprednisolone improves outcomes in critically ill patients with a hyperinflammatory phenotype. It will also evaluate the safety of methylprednisolone at different doses. The main questions it aims to answer are: * Does methylprednisolone improve organ function compared with placebo? * Does methylprednisolone reduce the risk of mortality within 30 days? Researchers will compare high-dose methylprednisolone (160mg/d), low-dose methylprednisolone (80mg/d), and placebo (normal saline) to evaluate effectiveness and safety. Participants will: * Receive high-dose methylprednisolone, low-dose methylprednisolone, or placebo every 12 hours for the first 3 days * Be reassessed on Day 4 based on their inflammatory status If the hyperinflammatory phenotype persists, the treatment dose will be reduced by half and continued until Day 7 or ICU discharge, whichever occurs first If the patient transitions to a hypoinflammatory phenotype, the study treatment will be discontinued * Be monitored daily in the intensive care unit for organ function, inflammatory status, and need for organ support * Be followed for up to 30 days after randomization to assess survival and recovery

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: QUADRUPLE
• Enrollment: 150 participants

Interventions

• DRUG: Methylprednisolone (MP) — Methylprednisolone 80 mg intravenously every 12 hours for the first 3 days. On day 4, prior to administration, patients will be reassessed; if the hyperinflammatory phenotype persists, the dose will be reduced to 40 mg every 12 hours and continued until day 7 or ICU discharge, whichever occurs first. Treatment will be discontinued if patients transition to a hypoinflammatory phenotype on day 4.
• DRUG: Methylprednisolone (MP) — Methylprednisolone 40 mg intravenously every 12 hours for the first 3 days. On day 4, prior to administration, patients will be reassessed; if the hyperinflammatory phenotype persists, the dose will be reduced to 20 mg every 12 hours and continued until day 7 or ICU discharge, whichever occurs first. Treatment will be discontinued if patients transition to a hypoinflammatory phenotype on day 4.
• DRUG: Placebo — Normal saline (100 mL) will be administered intravenously every 12 hours for the first 3 days. On day 4, patients will be reassessed prior to dosing; if the hyperinflammatory phenotype persists, normal saline (100 mL) will continue to be administered every 12 hours until day 7 or ICU discharge, whichever occurs first. Treatment will be discontinued if patients transition to a hypoinflammatory phenotype on day 4.

Primary Outcomes

• Proportion of patients with a decrease in mean SOFA score ≥1.4 points from baseline to Day 9 (From baseline (Day 1) to Day 9)

Secondary Outcomes

• 30-day Organ Support Free Days (OSFD) (From randomization to 30 days)
• 30-day mortality (From randomization to 30 days)
• Incidence and severity of adverse events and serious adverse events during treatment (During the treatment period (from randomization to Day 7 or ICU discharge, whichever occurs first))

Trial Locations

• Peking Union Medical College Hospital, Beijing, China

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