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Severe community-acquired pneumonia (sCAP) has a high mortality rate of 25-50%. Excessive host inflammatory responses contribute to poor outcomes. Corticosteroid therapy may provide benefit; however, the optimal dosage remains unclear, and it is uncertain whether all etiologies (e.g., Pneumocystis jirovecii, adenovirus, influenza) of sCAP can benefit equally.
This study will first establish a comprehensive trial platform based on a prospective sCAP cohort, embedding a randomized, multifactorial, adaptive platform trial (APT). The response-adaptive design will increase the likelihood of patients being assigned to more effective treatment arms, while Bayesian statistical modeling will dynamically assess the efficacy of interventions, allowing early achievement of study endpoints.
At the starting stage, two pathogen-specific APTs will be conducted, focusing on adenovirus- and pneumocystis Jirovecii-induced sCAP. Patients admitted to the ICU with confirmed diagnoses of adenovirus or pneumocystis Jirovecii-associated sCAP will be randomized into a control group or one of two corticosteroid dosage groups. The primary endpoint will be 28-day all-cause mortality. Completion of these APTs will provide a theoretical basis for novel anti-inflammatory strategies in sCAP.
Moreover, this platform will serve as an essential research infrastructure for the efficient evaluation of new therapeutic options in the event of emerging or re-emerging respiratory pathogens causing sCAP in the future.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Standard of Care | Placebo Comparator | Receive Standard of care for SCAP, including antibiotics and respiratory support. |
|
| Low dose steroids | Experimental | Intervention: Receive 0.5mg/kg Methylprednisolone |
|
| Moderate dose steroids | Experimental | Intervention: Receive 1.0mg/kg Methylprednisolone |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Low dose steroids | Drug | Receive 0.5mg/kg Methylprednisolone |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 28-day all cause mortality | death at 28th day after inclusion | 28 days from inclusion |
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Inclusion Criteria:
Admission to ICU;
Age ≥ 18 years;
Exclusion Criteria:
Confirmed diagnosis of hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP);
Expected death within 24 hours;
Presence of septic shock prior to randomization; â‘£ History of allergy or contraindications to corticosteroids (e.g., active gastrointestinal bleeding, severe osteoporosis, uncontrolled hyperglycemia, bone marrow suppression);
Active fungal (except Pneumocystis jirovecii), tuberculosis, or hepatitis infection;
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| Moderate dose steroids |
| Drug |
Receive 1.0mg/kg Methylprednisolone |
|
| Saline (0.9% NaCl) | Drug | Saline 100ml |
|
| ID | Term |
|---|---|
| D000098968 | Community-Acquired Pneumonia |
| ID | Term |
|---|---|
| D017714 | Community-Acquired Infections |
| D007239 | Infections |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| D013256 | Steroids |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |
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