Corticosteroids in Hyperinflammatory Phenotype of Critical Illness
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorBin Du
About this trial
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
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≥18 years.
Diagnosis of acute respiratory distress syndrome (ARDS) or sepsis.
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;
Disqualifiers
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.
Trial design
Design model
Parallel
Treatments tested in this trial
Methylprednisolone (MP)
DrugMethylprednisolone 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.
Methylprednisolone (MP)
DrugMethylprednisolone 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.
Placebo
DrugNormal 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.
Treatment groups
150 Participants
are divided into 3 treatment groupsGroup A: high dose methylprednisolone groupExperimental treatment 1 intervention
Group B: low dose methylprednisolone groupExperimental treatment 1 intervention
Group C: placebo groupPlacebo comparator 1 intervention
Trial outcomes
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.
Time frame
From baseline (Day 1) to Day 9Secondary outcomes
1
30-day Organ Support Free Days (OSFD)
Organ Support Free Days (OSFD) is defined as the number of days within 30 days where the patient survives without the need for any organ support, including respiratory support (mechanical ventilation and extracorporeal membrane oxygenation \[ECMO\]), circulatory support (vasopressors, positive inotropic agents, intra-aortic balloon pump \[IABP\], and ECMO), and renal replacement therapy. If the patient dies within 30 days, OSFD is recorded as 0 days.
Time frame
From randomization to 30 days2
30-day mortality
30-day mortality is defined as death from any cause within 30 days after randomization.
Time frame
From randomization to 30 days3
Incidence and severity of adverse events and serious adverse events during treatment
The outcome includes the incidence and severity of adverse events (AEs) and serious adverse events (SAEs) during the treatment period. Adverse events of interest include hyperglycemia (requiring insulin therapy in non-diabetic patients or increased insulin dosage in diabetic patients), gastrointestinal bleeding, muscle weakness, barotrauma (including pneumothorax, pneumomediastinum, subcutaneous emphysema, or imaging-confirmed findings), new-onset infection (hospital-acquired infections as determined by the treating physician), respiratory acidosis, severe acidosis (pH \< 7.10), refractory hypoxemia (PaO₂ \< 55 mmHg), severe hypotension (mean arterial pressure \< 60 mmHg), new-onset arrhythmia (including atrial fibrillation or supraventricular tachycardia), cardiac arrest, and all reported serious adverse events.
Time frame
During the treatment period (from randomization to Day 7 or ICU discharge, whichever occurs first)Other outcomes
1
Length of ICU stay
Length of ICU stay is defined as the time from randomization to ICU discharge. Patients who remain in the ICU at 30 days after randomization or die during ICU stay will be assigned a value of 30 days.
Time frame
From randomization to 30 days2
Length of hospital stay
Length of hospital stay is defined as the time from randomization to hospital discharge. Patients who remain hospitalized at 30 days after randomization or die during hospitalization will be assigned a value of 30 days.
Time frame
From randomization to 30 days3
30-day ventilator-free days (VFD)
Ventilator-free days (VFD) are defined as the number of days from successful extubation to 30 days after randomization. Successful extubation is defined as liberation from mechanical ventilation for at least 48 hours without reintubation. Patients who remain ventilated at 30 days or die within 30 days will be assigned 0 ventilator-free days.
Time frame
From randomization to 30 days4
30-day vasopressor-free days
Vasopressor-free days are defined as the number of days from the last discontinuation of circulatory support to 30 days after randomization. Circulatory support includes vasopressors, inotropic agents, intra-aortic balloon pump (IABP), and extracorporeal membrane oxygenation (ECMO). Discontinuation is defined as cessation of vasopressors and inotropes for at least 48 hours without reinitiation. Patients who remain on circulatory support at 30 days or die within 30 days will be assigned 0 vasopressor-free days.
Time frame
From randomization to 30 daysSponsors and contacts
Click on the lead sponsor to view all of their trials.
Bin Du
Lead sponsor
Peking Union Medical College Hospital
Sponsor institution
Source ClinicalTrials.gov