Clinical trials

Severe community-acquired pneumonia caused by adenovirus (hereafter referred to as severe adenovirus pneumonia) is one of the common forms of severe community-acquired pneumonia in immunocompetent adults. It predominantly affects young individuals, progresses rapidly, and is associated with a high incidence of respiratory failure and multiple organ dysfunction. At present, there is no effective antiviral therapy available in China, and the reported mortality rate ranges from 41.5% to 80%. How to effectively reduce the mortality of severe adenovirus pneumonia, on the basis of conventional supportive care, is crucial for improving the prognosis of critically ill patients and alleviating the burden on families and society. We are currently conducting an adaptive, randomized, open-label controlled trial aimed at reducing mortality in severe adenovirus pneumonia. The primary objective of this study is to evaluate the efficacy and safety of adjunctive corticosteroid therapy at different dosages, in addition to early standard supportive treatment, in lowering mortality among patients with severe adenovirus pneumonia.

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.

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.

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.

Pneumocystis jirovecii pneumonia (PJP) is one of the common severe complications in immunocompromised patients, with a reported mortality rate of 60-80%. Reducing mortality from PJP is crucial for improving outcomes in critically ill non-HIV immunocompromised patients and alleviating the burden on families and society. To address this medical challenge, our institution is conducting a study aimed at lowering PJP-related mortality. Specifically, we are performing an adaptive, randomized, open-label controlled trial in patients with severe PJP. The primary objective of this study is to scientifically evaluate the efficacy and safety of adjunctive corticosteroids at different dosages, in addition to early standard supportive care, for reducing mortality in severe PJP

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.