SepsisPhase 2CHIPNCT07511582
Corticosteroids in Hyperinflammatory Phenotype of Critical Illness
A Phase 2 study testing Methylprednisolone (MP) in people with Sepsis and Acute Respiratory Distress Syndrome, run by Bin Du at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sepsis, Acute Respiratory Distress Syndrome
- What is being tested?
- Methylprednisolone (MP)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 150 participants
- Where
- 1 siteChina
- Study dates
- 15 Apr 2026to 1 Jun 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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.
- 3. 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.
- 6. Randomization within 72 hours of ARDS or sepsis onset. 7. Provision of written informed consent by the patient or their legally authorized representative.
Who cannot join
- 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.
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- 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.
- Any other condition that, in the opinion of the treating physician or investigator, would make participation in the study inappropriate.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Peking Union Medical College Hospital
Beijing, Beijing Municipality, 100730
Bin Du, MD, 8601069155036, dubin98@gmail.com
About this study
Official title: Efficacy, Safety, and Tolerability of Methylprednisolone in Critically Ill Patients With the Hyperinflammatory Phenotype: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase II 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:
Read more
- 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
Read the detailed description
Background: Acute respiratory distress syndrome (ARDS) and sepsis are common critical illnesses associated with persistently high mortality. The lack of improvement in overall outcomes despite multiple interventions may be attributable to substantial biological heterogeneity. Both ARDS and sepsis can be classified into hyperinflammatory and hypoinflammatory phenotypes based on clinical variables and/or biomarkers. Previous retrospective and target trial emulation studies suggest differential treatment responses, with hyperinflammatory patients potentially benefiting from corticosteroid therapy.
Objective: The primary objective is to evaluate the preliminary efficacy signal of intravenous methylprednisolone, compared with placebo, in critically ill patients with a hyperinflammatory phenotype. The primary endpoint is the proportion of patients achieving a ≥1.4-point reduction in mean Sequential Organ Failure Assessment (SOFA) score from baseline to Day 9. Secondary objectives include evaluation of 30-day mortality, organ support-free days, safety, and tolerability, and to inform endpoint selection and dose optimization for a future phase III trial.
Study Design: This is a multicenter, randomized, double-blind, placebo-controlled phase II trial. Participants will be randomized using a centralized system with stratified permuted block randomization by study site, with varying block sizes to minimize predictability. Eligible participants will be assigned in a 1:1:1 ratio to high-dose methylprednisolone, low-dose methylprednisolone, or placebo.
Participants:
Inclusion Criteria: Participants must meet all of the following criteria:
① Age ≥18 years; ② Diagnosis of ARDS or sepsis; ③ ARDS defined according to standard criteria: acute onset within 1 week, bilateral opacities, respiratory failure not fully explained by cardiac causes, and PaO₂/FiO₂ ≤300 mmHg or SpO₂/FiO₂ ≤315 under PEEP ≥5 cmH₂O. Sepsis defined according to Sepsis-3 criteria (suspected or confirmed infection with SOFA increase ≥2); ④ Receiving invasive mechanical ventilation; ⑤ Admission to ICU; ⑥ Hyperinflammatory phenotype (predicted probability ≥0.5 using a clinical classifier); ⑦Randomization within 72 hours of ARDS or sepsis onset; ⑧Written informed consent from patient or legally authorized representative.
Exclusion Criteria: Participants meeting any of the following will be excluded:
① High-dose vasopressor requirement (norepinephrine ≥0.5 μg/kg/min or epinephrine ≥0.25 μg/kg/min); ② Recent cardiac surgery; ③ Conditions requiring high-dose corticosteroids; ④ Long-term systemic corticosteroid use within 6 months; ⑤ Pregnancy or lactation; ⑥ Brain death; ⑦ Advanced malignancy or expected survival <6 months; ⑧Known hypersensitivity to methylprednisolone; ⑨ Organ transplantation or hematopoietic stem cell transplantation; ⑩ Active life-threatening fungal infection or tuberculosis; ⑪ Neuromuscular disease affecting respiration; ⑫ Severe immunodeficiency (e.g., HIV, SCID); ⑬ Do-not-resuscitate (DNR) orders or withdrawal of care; ⑭ Participation in another interventional trial; ⑮ Any condition deemed unsuitable by investigator.
Sample Size: This phase II exploratory trial aims to estimate clinically meaningful effect sizes rather than formally test hypotheses. A total of 150 participants (50 per group) will be enrolled. Assuming a 10% dropout rate, approximately 45 evaluable participants per group are expected. Based on prior data, the control group is expected to have a 20% response rate, with treatment potentially increasing this to 40%. The 95% confidence interval half-width is estimated at ±18.5%, providing sufficient precision to inform a phase III trial.
Interventions: Participants will be randomized to: High-dose group: methylprednisolone 80 mg IV every 12 hours; Low-dose group: methylprednisolone 40 mg IV every 12 hours; or Placebo group: normal saline (100 mL) IV every 12 hours. All treatments will be identical in volume, appearance, and administration. At Day 4, inflammatory phenotype will be reassessed; treatment will be discontinued if phenotype transitions to hypoinflammatory. Otherwise, dose will be halved and continued until Day 7 or ICU discharge. All patients will receive standard ICU care according to guidelines.
Blinding: Double-blind design. Drug preparation will be performed by unblinded personnel, while investigators, clinicians, and patients remain blinded.
Outcomes: Primary outcome is proportion of patients achieving a ≥1.4-point reduction in mean SOFA score from baseline to Day 9. Mean SOFA change is calculated as baseline SOFA minus the average SOFA from Days 2-9. For patients who die before Day 9, SOFA is imputed as 24 thereafter; for discharged patients, last observation carried forward (LOCF) is applied. Secondary outcomes include 30-day all-cause mortality, 30-day organ support-free days (OSFD) and Incidence and severity of adverse events. Exploratory outcomes include ICU and hospital length of stay; ventilator-, vasopressor-, and RRT-free days; phenotype transition rates; biomarkers (CRP, PCT, IL-6, etc.); SOFA score trajectory; Vasoactive-Inotropic Score (VIS); incidence of new infections Statistical Analysis: Analyses will follow the intention-to-treat principle. Primary outcome will be reported as proportions with risk differences and 95% confidence intervals. Secondary and exploratory outcomes will be analyzed descriptively. Results will inform effect size estimation and design of a future phase III trial.
- Conditions
- Sepsis, Acute Respiratory Distress Syndrome
- Being tested
- Methylprednisolone (MP), Placebo
- Keywords
- Corticosteroids, Hyperinflammatory phenotype, Sepsis, Acute respiratory distress syndrome
- Medical subject headings
- Sepsis, Respiratory Distress Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
Methylprednisolone (MP)Drug
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From baseline (Day 1) to Day 9
Secondary outcomes (3)
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.
Measured: From randomization to 30 days
30-day mortality
30-day mortality is defined as death from any cause within 30 days after randomization.
Measured: From randomization to 30 days
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.
Measured: During the treatment period (from randomization to Day 7 or ICU discharge, whichever occurs first)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2026
- Study start15 Apr 2026
- Primary completion1 Apr 2028 (estimated)
- Study completion1 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (40)Papers the sponsor has linked to this study.
- Other trials for SepsisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Bin Du
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Bin Du, Peking Union Medical College Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07511582
- Sponsor's protocol ID
- K10358
- Acronym
- CHIP
- Status last verified
- May 2026
- First submitted
- 30 Mar 2026
- Last updated
- 26 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Tongyoo S, Permpikul C, Mongkolpun W, Vattanavanit V, Udompanturak S, Kocak M, Meduri GU. Hydrocortisone treatment in early sepsis-associated acute respiratory distress syndrome: results of a randomized controlled trial. Crit Care. 2016 Oct 15;20(1):329. doi: 10.1186/s13054-016-1511-2.
PubMed 27741949Maddali MV, Churpek M, Pham T, Rezoagli E, Zhuo H, Zhao W, He J, Delucchi KL, Wang C, Wickersham N, McNeil JB, Jauregui A, Ke S, Vessel K, Gomez A, Hendrickson CM, Kangelaris KN, Sarma A, Leligdowicz A, Liu KD, Matthay MA, Ware LB, Laffey JG, Bellani G, Calfee CS, Sinha P; LUNG SAFE Investigators and the ESICM Trials Group. Validation and utility of ARDS subphenotypes identified by machine-learning models using clinical data: an observational, multicohort, retrospective analysis. Lancet Respir Med. 2022 Apr;10(4):367-377. doi: 10.1016/S2213-2600(21)00461-6. Epub 2022 Jan 10.
PubMed 35026177McNicholas B, Madden MG, Laffey JG. Machine Learning Classifier Models: The Future for Acute Respiratory Distress Syndrome Phenotyping? Am J Respir Crit Care Med. 2020 Oct 1;202(7):919-920. doi: 10.1164/rccm.202006-2388ED. No abstract available.
PubMed 32687397Ranieri VM, Thompson BT, Barie PS, Dhainaut JF, Douglas IS, Finfer S, Gardlund B, Marshall JC, Rhodes A, Artigas A, Payen D, Tenhunen J, Al-Khalidi HR, Thompson V, Janes J, Macias WL, Vangerow B, Williams MD; PROWESS-SHOCK Study Group. Drotrecogin alfa (activated) in adults with septic shock. N Engl J Med. 2012 May 31;366(22):2055-64. doi: 10.1056/NEJMoa1202290. Epub 2012 May 22.
PubMed 22616830Pensier J, Fosset M, Paschold BS, von Wedel D, Redaelli S, Braeuer BLP, Novack V, Balzer F, Jung B, Amato MBP, Jaber S, Talmor D, Baedorf-Kassis E, Schaefer MS. Temporal stability of phenotypes of acute respiratory distress syndrome: clinical implications for early corticosteroid therapy and mortality. Intensive Care Med. 2025 Oct;51(10):1784-1796. doi: 10.1007/s00134-025-08089-4. Epub 2025 Aug 21.
PubMed 40839098Famous KR, Delucchi K, Ware LB, Kangelaris KN, Liu KD, Thompson BT, Calfee CS; ARDS Network. Acute Respiratory Distress Syndrome Subphenotypes Respond Differently to Randomized Fluid Management Strategy. Am J Respir Crit Care Med. 2017 Feb 1;195(3):331-338. doi: 10.1164/rccm.201603-0645OC.
PubMed 27513822Calfee CS, Delucchi KL, Sinha P, Matthay MA, Hackett J, Shankar-Hari M, McDowell C, Laffey JG, O'Kane CM, McAuley DF; Irish Critical Care Trials Group. Acute respiratory distress syndrome subphenotypes and differential response to simvastatin: secondary analysis of a randomised controlled trial. Lancet Respir Med. 2018 Sep;6(9):691-698. doi: 10.1016/S2213-2600(18)30177-2. Epub 2018 Aug 2.
PubMed 30078618Sinha P, Delucchi KL, Thompson BT, McAuley DF, Matthay MA, Calfee CS; NHLBI ARDS Network. Latent class analysis of ARDS subphenotypes: a secondary analysis of the statins for acutely injured lungs from sepsis (SAILS) study. Intensive Care Med. 2018 Nov;44(11):1859-1869. doi: 10.1007/s00134-018-5378-3. Epub 2018 Oct 5.
PubMed 30291376Sinha P, Kerchberger VE, Willmore A, Chambers J, Zhuo H, Abbott J, Jones C, Wickersham N, Wu N, Neyton L, Langelier CR, Mick E, He J, Jauregui A, Churpek MM, Gomez AD, Hendrickson CM, Kangelaris KN, Sarma A, Leligdowicz A, Delucchi KL, Liu KD, Russell JA, Matthay MA, Walley KR, Ware LB, Calfee CS. Identifying molecular phenotypes in sepsis: an analysis of two prospective observational cohorts and secondary analysis of two randomised controlled trials. Lancet Respir Med. 2023 Nov;11(11):965-974. doi: 10.1016/S2213-2600(23)00237-0. Epub 2023 Aug 23.
PubMed 37633303National Heart, Lung, and Blood Institute ARDS Clinical Trials Network; Truwit JD, Bernard GR, Steingrub J, Matthay MA, Liu KD, Albertson TE, Brower RG, Shanholtz C, Rock P, Douglas IS, deBoisblanc BP, Hough CL, Hite RD, Thompson BT. Rosuvastatin for sepsis-associated acute respiratory distress syndrome. N Engl J Med. 2014 Jun 5;370(23):2191-200. doi: 10.1056/NEJMoa1401520. Epub 2014 May 18.
PubMed 24835849National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network; Wiedemann HP, Wheeler AP, Bernard GR, Thompson BT, Hayden D, deBoisblanc B, Connors AF Jr, Hite RD, Harabin AL. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med. 2006 Jun 15;354(24):2564-75. doi: 10.1056/NEJMoa062200. Epub 2006 May 21.
PubMed 16714767Brower RG, Lanken PN, MacIntyre N, Matthay MA, Morris A, Ancukiewicz M, Schoenfeld D, Thompson BT; National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. N Engl J Med. 2004 Jul 22;351(4):327-36. doi: 10.1056/NEJMoa032193.
PubMed 15269312Delucchi K, Famous KR, Ware LB, Parsons PE, Thompson BT, Calfee CS; ARDS Network. Stability of ARDS subphenotypes over time in two randomised controlled trials. Thorax. 2018 May;73(5):439-445. doi: 10.1136/thoraxjnl-2017-211090. Epub 2018 Feb 24.
PubMed 29477989Sinha P, Delucchi KL, Chen Y, Zhuo H, Abbott J, Wang C, Wickersham N, McNeil JB, Jauregui A, Ke S, Vessel K, Gomez A, Hendrickson CM, Kangelaris KN, Sarma A, Leligdowicz A, Liu KD, Matthay MA, Ware LB, Calfee CS. Latent class analysis-derived subphenotypes are generalisable to observational cohorts of acute respiratory distress syndrome: a prospective study. Thorax. 2022 Jan;77(1):13-21. doi: 10.1136/thoraxjnl-2021-217158. Epub 2021 Jul 12.
PubMed 34253679Rajendran S, Xu Z, Pan W, Zang C, Siempos I, Torres L, Xu J, Bian J, Schenck EJ, Wang F. Multicenter target trial emulation to evaluate corticosteroids for sepsis stratified by predicted organ dysfunction trajectory. Nat Commun. 2025 May 13;16(1):4450. doi: 10.1038/s41467-025-59643-z.
PubMed 40360520
Study at a glance
From the registry record, last updated by the sponsor on 26 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy, Safety, and Tolerability of Methylprednisolone in Critically Ill Patients With the Hyperinflammatory Phenotype: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase II Trial
- ClinicalTrials.gov ID
- NCT07511582
- Acronym / sponsor ID
- CHIP / K10358
- Conditions
- Sepsis, Acute Respiratory Distress Syndrome
- Keywords
- Corticosteroids, Hyperinflammatory phenotype, Sepsis, Acute respiratory distress syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Bin DuUniversity, hospital or other
- Study start
- 15 Apr 2026 (actual)
- Primary completion
- 1 Apr 2028 (estimated)
- Study completion
- 1 Jun 2028 (estimated)
- First posted
- 6 Apr 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
Background: Acute respiratory distress syndrome (ARDS) and sepsis are common critical illnesses associated with persistently high mortality. The lack of improvement in overall outcomes despite multiple interventions may be attributable to substantial biological heterogeneity. Both ARDS and sepsis can be classified into hyperinflammatory and hypoinflammatory phenotypes based on clinical variables and/or biomarkers. Previous retrospective and target trial emulation studies suggest differential treatment responses, with hyperinflammatory patients potentially benefiting from corticosteroid therapy.
Objective: The primary objective is to evaluate the preliminary efficacy signal of intravenous methylprednisolone, compared with placebo, in critically ill patients with a hyperinflammatory phenotype. The primary endpoint is the proportion of patients achieving a ≥1.4-point reduction in mean Sequential Organ Failure Assessment (SOFA) score from baseline to Day 9. Secondary objectives include evaluation of 30-day mortality, organ support-free days, safety, and tolerability, and to inform endpoint selection and dose optimization for a future phase III trial.
Study Design: This is a multicenter, randomized, double-blind, placebo-controlled phase II trial. Participants will be randomized using a centralized system with stratified permuted block randomization by study site, with varying block sizes to minimize predictability. Eligible participants will be assigned in a 1:1:1 ratio to high-dose methylprednisolone, low-dose methylprednisolone, or placebo.
Participants:
Inclusion Criteria: Participants must meet all of the following criteria:
① Age ≥18 years; ② Diagnosis of ARDS or sepsis; ③ ARDS defined according to standard criteria: acute onset within 1 week, bilateral opacities, respiratory failure not fully explained by cardiac causes, and PaO₂/FiO₂ ≤300 mmHg or SpO₂/FiO₂ ≤315 under PEEP ≥5 cmH₂O. Sepsis defined according to Sepsis-3 criteria (suspected or confirmed infection with SOFA increase ≥2); ④ Receiving invasive mechanical ventilation; ⑤ Admission to ICU; ⑥ Hyperinflammatory phenotype (predicted probability ≥0.5 using a clinical classifier); ⑦Randomization within 72 hours of ARDS or sepsis onset; ⑧Written informed consent from patient or legally authorized representative.
Exclusion Criteria: Participants meeting any of the following will be excluded:
① High-dose vasopressor requirement (norepinephrine ≥0.5 μg/kg/min or epinephrine ≥0.25 μg/kg/min); ② Recent cardiac surgery; ③ Conditions requiring high-dose corticosteroids; ④ Long-term systemic corticosteroid use within 6 months; ⑤ Pregnancy or lactation; ⑥ Brain death; ⑦ Advanced malignancy or expected survival <6 months; ⑧Known hypersensitivity to methylprednisolone; ⑨ Organ transplantation or hematopoietic stem cell transplantation; ⑩ Active life-threatening fungal infection or tuberculosis; ⑪ Neuromuscular disease affecting respiration; ⑫ Severe immunodeficiency (e.g., HIV, SCID); ⑬ Do-not-resuscitate (DNR) orders or withdrawal of care; ⑭ Participation in another interventional trial; ⑮ Any condition deemed unsuitable by investigator.
Sample Size: This phase II exploratory trial aims to estimate clinically meaningful effect sizes rather than formally test hypotheses. A total of 150 participants (50 per group) will be enrolled. Assuming a 10% dropout rate, approximately 45 evaluable participants per group are expected. Based on prior data, the control group is expected to have a 20% response rate, with treatment potentially increasing this to 40%. The 95% confidence interval half-width is estimated at ±18.5%, providing sufficient precision to inform a phase III trial.
Interventions: Participants will be randomized to: High-dose group: methylprednisolone 80 mg IV every 12 hours; Low-dose group: methylprednisolone 40 mg IV every 12 hours; or Placebo group: normal saline (100 mL) IV every 12 hours. All treatments will be identical in volume, appearance, and administration. At Day 4, inflammatory phenotype will be reassessed; treatment will be discontinued if phenotype transitions to hypoinflammatory. Otherwise, dose will be halved and continued until Day 7 or ICU discharge. All patients will receive standard ICU care according to guidelines.
Blinding: Double-blind design. Drug preparation will be performed by unblinded personnel, while investigators, clinicians, and patients remain blinded.
Outcomes: Primary outcome is proportion of patients achieving a ≥1.4-point reduction in mean SOFA score from baseline to Day 9. Mean SOFA change is calculated as baseline SOFA minus the average SOFA from Days 2-9. For patients who die before Day 9, SOFA is imputed as 24 thereafter; for discharged patients, last observation carried forward (LOCF) is applied. Secondary outcomes include 30-day all-cause mortality, 30-day organ support-free days (OSFD) and Incidence and severity of adverse events. Exploratory outcomes include ICU and hospital length of stay; ventilator-, vasopressor-, and RRT-free days; phenotype transition rates; biomarkers (CRP, PCT, IL-6, etc.); SOFA score trajectory; Vasoactive-Inotropic Score (VIS); incidence of new infections Statistical Analysis: Analyses will follow the intention-to-treat principle. Primary outcome will be reported as proportions with risk differences and 95% confidence intervals. Secondary and exploratory outcomes will be analyzed descriptively. Results will inform effect size estimation and design of a future phase III trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| high dose methylprednisolone group | Experimental | 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. |
| low dose methylprednisolone group | Experimental | 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. |
| placebo group | Placebo comparator | Drug: PlaceboNormal 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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;
- respiratory failure not fully explained by cardiac failure or fluid overload;
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | high dose methylprednisolone group |
| 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 | low dose methylprednisolone group |
| PlaceboNormal 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 group |
Primary outcome
Proportion of patients with a decrease in mean Sequential Organ Failure Assessment (SOFA) score ≥1.4 points from baseline to Day 9
Time frame: From baseline (Day 1) 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.
3 secondary outcomes
30-day Organ Support Free Days (OSFD)
Time frame: From randomization to 30 days
30-day mortality
Time frame: From randomization to 30 days
Incidence and severity of adverse events and serious adverse events during treatment
Time frame: During the treatment period (from randomization to Day 7 or ICU discharge, whichever occurs first)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 May 2026.
- Background: PubMed 27741949Tongyoo S, Permpikul C, Mongkolpun W, Vattanavanit V, Udompanturak S, Kocak M, Meduri GU. Hydrocortisone treatment in early sepsis-associated acute respiratory distress syndrome: results of a randomized controlled trial. Crit Care. 2016 Oct 15;20(1):329. doi: 10.1186/s13054-016-1511-2.
- Background: PubMed 35026177Maddali MV, Churpek M, Pham T, Rezoagli E, Zhuo H, Zhao W, He J, Delucchi KL, Wang C, Wickersham N, McNeil JB, Jauregui A, Ke S, Vessel K, Gomez A, Hendrickson CM, Kangelaris KN, Sarma A, Leligdowicz A, Liu KD, Matthay MA, Ware LB, Laffey JG, Bellani G, Calfee CS, Sinha P; LUNG SAFE Investigators and the ESICM Trials Group. Validation and utility of ARDS subphenotypes identified by machine-learning models using clinical data: an observational, multicohort, retrospective analysis. Lancet Respir Med. 2022 Apr;10(4):367-377. doi: 10.1016/S2213-2600(21)00461-6. Epub 2022 Jan 10.
- Background: PubMed 32687397McNicholas B, Madden MG, Laffey JG. Machine Learning Classifier Models: The Future for Acute Respiratory Distress Syndrome Phenotyping? Am J Respir Crit Care Med. 2020 Oct 1;202(7):919-920. doi: 10.1164/rccm.202006-2388ED. No abstract available.
- Background: PubMed 22616830Ranieri VM, Thompson BT, Barie PS, Dhainaut JF, Douglas IS, Finfer S, Gardlund B, Marshall JC, Rhodes A, Artigas A, Payen D, Tenhunen J, Al-Khalidi HR, Thompson V, Janes J, Macias WL, Vangerow B, Williams MD; PROWESS-SHOCK Study Group. Drotrecogin alfa (activated) in adults with septic shock. N Engl J Med. 2012 May 31;366(22):2055-64. doi: 10.1056/NEJMoa1202290. Epub 2012 May 22.
- Background: PubMed 40839098Pensier J, Fosset M, Paschold BS, von Wedel D, Redaelli S, Braeuer BLP, Novack V, Balzer F, Jung B, Amato MBP, Jaber S, Talmor D, Baedorf-Kassis E, Schaefer MS. Temporal stability of phenotypes of acute respiratory distress syndrome: clinical implications for early corticosteroid therapy and mortality. Intensive Care Med. 2025 Oct;51(10):1784-1796. doi: 10.1007/s00134-025-08089-4. Epub 2025 Aug 21.
- Background: PubMed 27513822Famous KR, Delucchi K, Ware LB, Kangelaris KN, Liu KD, Thompson BT, Calfee CS; ARDS Network. Acute Respiratory Distress Syndrome Subphenotypes Respond Differently to Randomized Fluid Management Strategy. Am J Respir Crit Care Med. 2017 Feb 1;195(3):331-338. doi: 10.1164/rccm.201603-0645OC.
- Background: PubMed 30078618Calfee CS, Delucchi KL, Sinha P, Matthay MA, Hackett J, Shankar-Hari M, McDowell C, Laffey JG, O'Kane CM, McAuley DF; Irish Critical Care Trials Group. Acute respiratory distress syndrome subphenotypes and differential response to simvastatin: secondary analysis of a randomised controlled trial. Lancet Respir Med. 2018 Sep;6(9):691-698. doi: 10.1016/S2213-2600(18)30177-2. Epub 2018 Aug 2.
- Background: PubMed 30291376Sinha P, Delucchi KL, Thompson BT, McAuley DF, Matthay MA, Calfee CS; NHLBI ARDS Network. Latent class analysis of ARDS subphenotypes: a secondary analysis of the statins for acutely injured lungs from sepsis (SAILS) study. Intensive Care Med. 2018 Nov;44(11):1859-1869. doi: 10.1007/s00134-018-5378-3. Epub 2018 Oct 5.
- Background: PubMed 37633303Sinha P, Kerchberger VE, Willmore A, Chambers J, Zhuo H, Abbott J, Jones C, Wickersham N, Wu N, Neyton L, Langelier CR, Mick E, He J, Jauregui A, Churpek MM, Gomez AD, Hendrickson CM, Kangelaris KN, Sarma A, Leligdowicz A, Delucchi KL, Liu KD, Russell JA, Matthay MA, Walley KR, Ware LB, Calfee CS. Identifying molecular phenotypes in sepsis: an analysis of two prospective observational cohorts and secondary analysis of two randomised controlled trials. Lancet Respir Med. 2023 Nov;11(11):965-974. doi: 10.1016/S2213-2600(23)00237-0. Epub 2023 Aug 23.
- Background: PubMed 24835849National Heart, Lung, and Blood Institute ARDS Clinical Trials Network; Truwit JD, Bernard GR, Steingrub J, Matthay MA, Liu KD, Albertson TE, Brower RG, Shanholtz C, Rock P, Douglas IS, deBoisblanc BP, Hough CL, Hite RD, Thompson BT. Rosuvastatin for sepsis-associated acute respiratory distress syndrome. N Engl J Med. 2014 Jun 5;370(23):2191-200. doi: 10.1056/NEJMoa1401520. Epub 2014 May 18.
- Background: PubMed 16714767National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network; Wiedemann HP, Wheeler AP, Bernard GR, Thompson BT, Hayden D, deBoisblanc B, Connors AF Jr, Hite RD, Harabin AL. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med. 2006 Jun 15;354(24):2564-75. doi: 10.1056/NEJMoa062200. Epub 2006 May 21.
- Background: PubMed 15269312Brower RG, Lanken PN, MacIntyre N, Matthay MA, Morris A, Ancukiewicz M, Schoenfeld D, Thompson BT; National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. N Engl J Med. 2004 Jul 22;351(4):327-36. doi: 10.1056/NEJMoa032193.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Methylprednisolone (MP) in people with Sepsis and Acute Respiratory Distress Syndrome, run by Bin Du at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 26 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Bin Du (+86 6916 5643, dubin98@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients with a decrease in mean Sequential Organ Failure Assessment (SOFA) score ≥1.4 points from baseline to Day 9 (time frame: From baseline (Day 1) to Day 9). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07511582, which also lists 40 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 May 2026; AzTrials last refreshed its copy on 6 Nov 2026.