Adaptive RCT of Corticosteroids for Severe Influenza Pneumonia in Adults

NCT07351500 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: 2025-I2M-C&T-B-090C
• Study Type: interventional
• Target: 496
• Locations: 0 countries
• Sites: N/A

Brief Summary

Severe community-acquired pneumonia caused by influenza virus (hereafter referred to as severe influenza pneumonia) is a major etiology of community-acquired pneumonia leading to acute respiratory failure and ICU admission. It can rapidly progress to profound hypoxemia, acute respiratory distress syndrome (ARDS), and multiple organ dysfunction, and remains associated with substantial mortality. Although antiviral therapy-typically neuraminidase inhibitors-and well-established organ-support strategies are currently available, outcomes in a subset of critically ill patients remain poor despite antiviral and supportive care alone, with ICU mortality reported to be as high as 20-30%. Therefore, identifying effective adjunctive interventions beyond standard care to further reduce mortality in severe influenza pneumonia is of great clinical importance for improving outcomes in critically ill patients and alleviating the burden on families and society. However, the use of systemic corticosteroids in influenza-associated community-acquired pneumonia (CAP) has long been highly controversial. Multiple studies have suggested that corticosteroid therapy may increase mortality among patients with H1N1 influenza. During the early phase of the COVID-19 pandemic, treatment strategies drew on this evidence and generally advised caution regarding corticosteroid use; subsequently, randomized controlled trials (RCTs) such as RECOVERY and REMAP-CAP demonstrated that low-dose corticosteroids (e.g., dexamethasone 6 mg/day) reduce mortality in patients with pneumonia requiring oxygen therapy. Recently, the U.S. Centers for Disease Control and Prevention (CDC) has emphasized the urgent need for RCTs evaluating low- to moderate-dose corticosteroids or other immunomodulatory agents to clarify their role in the management of influenza-associated CAP. Collectively, these observations underscore the urgency of pathogen-directed anti-inflammatory strategies for CAP-associated acute respiratory failure. 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 (including guideline-concordant antiviral therapy and organ support), for reducing mortality in patients with severe influenza pneumonia.

Conditions

Influenza

Keywords

Influenza; community-acquired pneumonia; adaptive randomised controled trial; corticosteroids

Outcome Measures

Primary Outcomes (1)

• 28-day all cause mortality

  28 days from inclusion

Study Arms (3)

Standard of Care

PLACEBO COMPARATOR

Control group

Drug: Saline (0.9%, sterile, for infusion)

Low dose steroids

EXPERIMENTAL

treated with low dose corticosteroids

Drug: low dose Methylprednisolone

Moderate dose steroids

EXPERIMENTAL

treated with moderate dose corticosteroids

Drug: Moderate dose Methylprednisolone

Interventions

low dose Methylprednisolone DRUG

Methylprednisolone 0.5mg/kg ivgtt qd

Low dose steroids

Moderate dose Methylprednisolone DRUG

Methylprednisolone 1.0mg/kg ivgtt qd

Moderate dose steroids

Saline (0.9%, sterile, for infusion) DRUG

Sailine as control

Standard of Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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);

You may not qualify if:

• 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.

Sponsors & Collaborators

• Qingyuan Zhan: lead

MeSH Terms

Conditions

Influenza, Human; Community-Acquired Pneumonia

Interventions

Sodium Chloride; Methylprednisolone

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Community-Acquired Infections; Pneumonia

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: January 12, 2026
• First Posted: January 20, 2026
• Study Start: January 15, 2026
• Primary Completion (Estimated): November 30, 2028
• Study Completion (Estimated): November 30, 2028
• Last Updated: January 20, 2026

Record last verified: 2026-01