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

Phase 2Not Yet RecruitingNCT07357935

Qingyuan Zhan500 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

500

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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. \- 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. \-

Outcomes

Primary Outcomes

90-day all-cause mortality

The proportion of participants who die from any cause within 90 days after enrollment.

Time frame: At Day 90 (from enrollment)

28-day all-cause mortality

The proportion of participants who die from any cause within 28 days after enrollment.

Time frame: : At Day 28 (from enrollment)

Secondary Outcomes

Incidence of glucocorticoid-related adverse events (AEs)

The occurrence of AEs known to be associated with glucocorticoid therapy, including but not limited to: secondary infection, hyperglycemia, myopathy/weakness, gastrointestinal bleeding, sodium/water retention, and inflammatory rebound.

Time frame: From the first dose of methylprednisolone up to Day 28 (the end of the primary safety observation period).

Proportion of participants with glucocorticoid responsiveness at Day 4

The proportion of participants who meet the pre-defined criteria for glucocorticoid responsiveness at Day 4 (D4) after initiating treatment. Responsiveness is defined as: an improvement in the oxygenation index (PFR) by ≥20% AND a decrease in Sequential Organ Failure Assessment (SOFA) score by ≥2 points compared to baseline (D1).

Time frame: At Day 4 (from enrollment)