Adaptive RCT of Corticosteroids for Severe Chlamydia Psittaci Pneumonia in Adults

Official title

An Embedded Adaptive Randomized Controlled Trial of Corticosteroid Therapy for Severe Chlamydia Psittaci Community-Acquired Pneumonia in Adults

Overview

Severe community-acquired pneumonia caused by psittacosis is a form of atypical-pathogen community-acquired pneumonia that often requires critical care management. It can occur in immunocompetent adults, has an abrupt onset and rapid progression, and may quickly deteriorate to profound hypoxemia, acute respiratory distress syndrome, and multiple organ dysfunction, frequently necessitating ICU admission. In a multicenter cohort from 19 tertiary hospitals in China with metagenomic next-generation sequencing (mNGS)-confirmed severe CAP complicated by acute hypoxemic respiratory failure, approximately 44% of patients required invasive mechanical ventilation and ICU mortality was 8.9%, indicating a substantial risk of death and severe morbidity among critically ill patients. The World Health Organization (WHO) reported an increase in cases across several European countries from 2023 to early 2024, with five deaths, suggesting that the disease burden and public health significance of psittacosis may have been underestimated for a prolonged period. At present, the cornerstone of psittacosis pneumonia management is early recognition and timely pathogen-directed antibiotic therapy (tetracyclines, particularly doxycycline, as first-line treatment), together with well-established organ-support strategies. Optimizing comprehensive management beyond early standard supportive care and guideline-concordant antimicrobial therapy (including targeted antibiotics and organ support) to further reduce mortality in severe psittacosis pneumonia is therefore of major clinical importance for improving outcomes in critically ill patients and alleviating the burden on families and society. Accordingly, we plan to conduct an adaptive, randomized, open-label, controlled trial to evaluate the efficacy and safety of adjunctive corticosteroid regimens at different doses, in addition to early standard supportive care, for reducing mortality in patients with severe psittacosis pneumonia.

Interventions

• Drug Saline (0.9%, sterile, for infusion)
  Sailine as control
• Drug low dose Methylprednisolone
  Methylprednisolone 0.5mg/kg ivgtt qd
• Drug Moderate dose Methylprednisolone
  Methylprednisolone 1.0mg/kg ivgtt qd

Primary outcome measures

• 28-day all cause mortality [Time frame: 28 days from inclusion]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years.
• Admission to the Intensive Care Unit (ICU).
• Meeting the diagnostic criteria for community-acquired pneumonia (CAP).
• Meeting at least one of the major diagnostic criteria for severe pneumonia:

(i) Requirement for endotracheal intubation and mechanical ventilation;

(ii) Septic shock requiring vasopressor therapy after adequate fluid resuscitation.

-Or simultaneously fulfilling three of the minor criteria:

(i) Respiratory rate ≥ 30 breaths/min;

(ii) PaO₂/FiO₂ ≤ 250 mmHg;

(iii) Multilobar infiltrates;

(iv) Altered mental status and/or disorientation;

(v) Blood urea nitrogen ≥ 20 mg/dL (7.12 mmol/L);

(vi) Leukopenia (white blood cell count < 4 × 10⁹/L);

(vii) Thrombocytopenia (platelet count < 100 × 10⁹/L);

(viii) Hypothermia (core temperature < 36 °C);

(ix) Hypotension (systolic blood pressure < 90 mmHg) requiring aggressive fluid resuscitation.

• Confirmed Chlamydia psittaci etiology (psittacosis): at least one positive nucleic acid test (PCR/RT-PCR) or next-generation sequencing (NGS) result for Chlamydia psittaci in respiratory specimens (respiratory secretions, throat swabs, or bronchoalveolar lavage fluid).
• Severe community-acquired pneumonia (SCAP) patients admitted to the emergency department/ward/ICU due to respiratory failure within < 72 hours.
• Signed informed consent.

Exclusion criteria

• Patients receiving vasopressor therapy for septic shock at the time of enrollment.
• Terminally ill patients (expected survival <30 days, e.g., advanced malignancy).
• Clinical history suggesting overt aspiration.
• Documented active gastrointestinal bleeding.
• Presence of cystic fibrosis, obstructive pneumonia, active influenza, pulmonary tuberculosis, or fungal infection.
• Active viral hepatitis or active herpesvirus infection.
• Bone marrow suppression or HIV infection.
• Refusal of mechanical ventilation and endotracheal intubation.
• Uncontrolled hyperglycemia (diabetic ketoacidosis with blood ketones >3 mmol/L, or hyperosmolar hyperglycemic state with blood glucose >33.3 mmol/L and elevated osmolality).
• Known allergy to corticosteroids.
• Patients requiring anti-inflammatory corticosteroids or replacement hydrocortisone for any reason, or those already receiving prednisone >15 mg/day (or equivalent dose of another corticosteroid).
• Pregnant or breastfeeding women.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07352865 · 2025-I2M-C&T-B-090D

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗