Corticosteroids in Hyperinflammatory Phenotype of Critical Illness

NCT07511582 | Recruiting Phase 2 DMC

• 1 other identifier: K10358
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Sepsis; Acute Respiratory Distress Syndrome

Keywords

Corticosteroids; Hyperinflammatory phenotype; Sepsis; Acute respiratory distress syndrome

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with a decrease in mean Sequential Organ Failure Assessment (SOFA) score ≥1.4 points from baseline to Day 9

  The outcome is defined as the proportion of patients achieving a decrease of ≥1.4 points in mean SOFA score from baseline to Day 9. The mean change in SOFA score is calculated as the baseline SOFA score (Day 1) minus the average SOFA score from Days 2 through 9.The lowest possible SOFA score is 0, and the highest is 24. The higher the score, the more severe the organ dysfunction.

  From baseline (Day 1) to Day 9

Secondary Outcomes (3)

• 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)

Other Outcomes (9)

• Length of ICU stay

  From randomization to 30 days

• Length of hospital stay

  From randomization to 30 days

• 30-day ventilator-free days (VFD)

  From randomization to 30 days

Study Arms (3)

high dose methylprednisolone group

EXPERIMENTAL

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)

low dose methylprednisolone group

EXPERIMENTAL

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: Methylprednisolone (MP)

placebo group

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Methylprednisolone (MP) DRUG

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.

high dose methylprednisolone group

Placebo DRUG

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.

placebo group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must meet all of the following criteria:
• Age ≥18 years.
• Diagnosis of acute respiratory distress syndrome (ARDS) or sepsis.
• ARDS will be defined according to standard criteria:
• acute onset within 1 week of a known clinical insult or new/worsening respiratory symptoms;
• bilateral pulmonary opacities on chest imaging (X-ray or CT) or bilateral B-lines and/or consolidation on lung ultrasound, not fully explained by effusion, atelectasis, or nodules;
• respiratory failure not fully explained by cardiac failure or fluid overload;
• hypoxemia defined as PaO₂/FiO₂ ≤300 mmHg or SpO₂/FiO₂ ≤315 (with SpO₂ ≤97%) under a minimum positive end-expiratory pressure (PEEP) of 5 cmH₂O.
• Sepsis will be defined according to the Sepsis-3 criteria as suspected or confirmed infection with an acute increase in SOFA score ≥2 points, assuming a baseline SOFA score of 0 in patients without known prior organ dysfunction.
• Sepsis-associated ARDS will be defined as ARDS occurring in patients with sepsis.
• \. Receiving invasive mechanical ventilation. 4. Admission to the intensive care unit (ICU). 5. Hyperinflammatory phenotype, defined as a predicted probability ≥0.5 using a validated AI clinical classifier based on clinical data.
• \. Randomization within 72 hours of ARDS or sepsis onset. 7. Provision of written informed consent by the patient or their legally authorized representative.

You may not qualify if:

• Participants meeting any of the following criteria will be excluded:
• Requirement for high-dose vasopressor support, defined as norepinephrine ≥0.5 μg/kg/min or epinephrine ≥0.25 μg/kg/min.
• Post-cardiac surgery patients (e.g., coronary artery bypass grafting or valve replacement).
• Conditions requiring systemic corticosteroid therapy exceeding 1 mg/kg methylprednisolone or an equivalent dose (e.g., acute asthma exacerbation, acute exacerbation of chronic obstructive pulmonary disease, or autoimmune diseases).
• Long-term systemic corticosteroid use within the past 6 months.
• Pregnancy or lactation.
• Brain death.
• Advanced malignancy or other end-stage disease with an expected survival of less than 6 months, or anticipated death within 24 hours.
• Known hypersensitivity to methylprednisolone, including but not limited to urticaria, eczema, angioedema, bronchospasm, or anaphylaxis.
• History of solid organ transplantation or allogeneic hematopoietic stem cell transplantation.
• Active life-threatening fungal infection or tuberculosis.
• Neuromuscular disorders affecting spontaneous respiration.
• Severe inherited or acquired immunodeficiency (e.g., human immunodeficiency virus infection, chronic granulomatous disease, or severe combined immunodeficiency).
• Do-not-resuscitate (DNR) orders or withdrawal of life-sustaining treatment.
• Concurrent participation in another interventional clinical trial.

Sponsors & Collaborators

• Bin Du: lead

Study Sites (1)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

RECRUITING

Related Publications (40)

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MeSH Terms

Conditions

Sepsis; Respiratory Distress Syndrome

Interventions

Methylprednisolone

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Intervention Hierarchy (Ancestors)

Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Central Study Contacts

Bin Du

CONTACT

+86 6916 5643; dubin98@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Senior Consultant Physician; Professor

Study Record Dates

• First Submitted: March 30, 2026
• First Posted: April 6, 2026
• Study Start: April 15, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: May 26, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)