Early Inflammatory-Immune Stratification and Precision Glucocorticoid Intervention in Acute Respiratory Failure Induced by Community-Acquired Pneumonia

Qingyuan Zhan

Status and phase: Not yet enrolling; Phase 2; Phase 1

Conditions: Community-Acquired Pneumonia; Acute Respiratory Failure

Treatments: Drug: Methylprednisolone

Study type: Interventional

Funder types: Other

Identifiers

NCT07357935

2025ZD01902401

Details and patient eligibility

About

This is a prospective, multicenter, interventional cohort study aimed at constructing a high-quality, dynamic multimodal database for patients with acute respiratory failure caused by community-acquired pneumonia (CAP-ARF). The study focuses on bacterial CAP-ARF patients receiving standardized glucocorticoid therapy to investigate the heterogeneity of treatment responses under different etiologies and immune statuses. The goal is to provide a data foundation for precise immune stratification and identification of glucocorticoid-sensitive populations.

Full description

This study is part of the National Major Science and Technology Project for the Prevention and Control of Emerging and Major Infectious Diseases. It integrates existing multicenter cohorts (including healthy individuals, non-infectious ARF, mild CAP, and CAP-ARF patients) and establishes a prospective, standardized glucocorticoid intervention cohort for bacterial CAP-ARF. Eligible patients (age ≥18, admitted to ICU ≤48 hours, meeting bacterial pneumonia and severe ARF criteria) are treated with methylprednisolone based on initial oxygenation index (PFR ≤150 mmHg: 1 mg/kg/d; PFR >150 mmHg: 0.5 mg/kg/d). Dosing is adjusted at day 4 based on clinical response (improvement in oxygenation and SOFA score), with a total treatment duration of 7 days. Multimodal data-including clinical information, inflammatory/immune biomarkers, chest CT imaging, and multi-omics sequencing (transcriptomics, proteomics, metabolomics)-are collected at multiple timepoints (baseline, day 4, day 8). The database will support the analysis of immune-inflammatory profiles, identification of glucocorticoid-responsive subgroups, and development of precision intervention strategies for CAP-ARF.

Enrollment: 500 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:1. Age ≥ 18 years. 2. Admitted to the Intensive Care Unit (ICU) within 48 hours. 3. Meet diagnostic criteria for bacterial community-acquired pneumonia (CAP). 4. Meet at least one severity criterion: a) Receiving mechanical ventilation for acute respiratory failure with PEEP ≥ 5 cmH2O; OR b) On high-flow oxygen with FiO2 ≥ 0.5 and PaO2/FiO2 ratio ≤ 250 mmHg; OR c) On a reservoir oxygen mask with PaO2 below the specified flow threshold (see protocol). 5. Signed informed consent.

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Exclusion Criteria: 1. Suspected aspiration pneumonia. 2. Invasive mechanical ventilation within 14 days prior to admission. 3. Diagnosis of hospital-acquired or ventilator-associated pneumonia (HAP/VAP). 4. Positive for influenza virus, active tuberculosis, or fungal infection (except Pneumocystis jirovecii). 5. Active viral hepatitis or herpesvirus infection. 6. Hypersensitivity to glucocorticoids, or contraindications as judged by the investigator (e.g., severe concurrent infections, active gastrointestinal hemorrhage). 7. High-dose glucocorticoid therapy (>1 mg/kg/day prednisone equivalent) within 30 days for underlying disease. 8. Death within 24 hours of ICU admission. 9. Pregnancy or lactation. 10. Participation in other interventional studies or refusal to participate.

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Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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500 participants in 1 patient group

Standardized Methylprednisolone Intervention (Dose-Adjusted)

Experimental group

Description:

All enrolled patients receive intravenous methylprednisolone (0.5-1 mg/kg/day, dissolved in 100ml normal saline, once daily) for a total of 7 days. The initial dose is determined by the oxygenation index (PFR) at enrollment: * PFR ≤ 150 mmHg: Methylprednisolone 1 mg/kg/day. * PFR \> 150 mmHg: Methylprednisolone 0.5 mg/kg/day. At day 4 (D4), the dose is halved if the patient shows a clinical response (defined as an improvement in the oxygenation index ≥20% AND a decrease in SOFA score ≥2 points); otherwise, the original dose is maintained. Methylprednisolone is discontinued upon death or transfer out of the ICU. All patients also receive standard care for bacterial CAP-ARF as determined by the treating physician.

Treatment:

Drug: Methylprednisolone