Adaptive RCT of Corticosteroids for Severe Influenza Pneumonia in Adults

Официальное название

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

Обзор

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.

Вмешательства

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

Первичные конечные точки

• 28-day all cause mortality [Срок оценки: 28 days from inclusion]

Критерии участия

Критерии включения

• 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 influenza virus etiology: at least one positive nucleic acid test (RT-PCR/PCR) or next-generation sequencing (NGS) result for influenza virus 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07351500 · 2025-I2M-C&T-B-090C

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗