Randomized, Embedded, Multifactorial, Adaptive Platform Trial of Pathogen-Directed Precision Anti-inflammatory Therapy in Severe Community-Acquired Pneumonia(Core Protocal)
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 1,500
- 主要终点
- 28-day all cause mortality
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Admission to ICU;
- •Age ≥ 18 years;
- •ICU length of stay ≤ 48 hours; ④ Meeting the IDSA/ATS diagnostic criteria for SCAP.
排除标准
- •Confirmed diagnosis of hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP);
- •Expected death within 24 hours;
- •Presence of septic shock prior to randomization; ④ 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;
- •Receiving ongoing corticosteroid therapy at a dose equivalent to prednisone > 1 mg/kg/day due to underlying disease; ⑦ Participation in this trial within the past 90 days; ⑧ Refusal to sign informed consent.
研究组 & 干预措施
Standard of Care
Receive Standard of care for SCAP, including antibiotics and respiratory support.
干预措施: Saline (0.9% NaCl) (Drug)
Low dose steroids
Intervention: Receive 0.5mg/kg Methylprednisolone
干预措施: Low dose steroids (Drug)
Moderate dose steroids
Intervention: Receive 1.0mg/kg Methylprednisolone
干预措施: Moderate dose steroids (Drug)
结局指标
主要结局
28-day all cause mortality
时间窗: 28 days from inclusion
death at 28th day after inclusion
次要结局
未报告次要终点
研究者
Qingyuan Zhan
Director
China-Japan Friendship Hospital