How Long Should we Give Steroids for Patients With Severe PCP (HOW LONG)
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 416
- 试验地点
- 2
- 主要终点
- Hierarchical composite clinical outcome
研究概览
简要总结
The HOW LONG trial is an international, multicenter, Phase IV randomized clinical trial evaluating the optimal duration of adjunctive systemic corticosteroids in immunocompromised adults with severe Pneumocystis jirovecii pneumonia (PCP) who demonstrate early clinical recovery. Participants who no longer require supplemental oxygen by day 10 of corticosteroid therapy are randomized to discontinue corticosteroids at day 10 (or hospital discharge, if earlier) versus continue corticosteroids for a total of 21 days. The trial assesses whether earlier discontinuation reduces steroid-related complications while maintaining clinical outcomes.
详细描述
Adjunctive systemic corticosteroids are routinely used in severe PCP to reduce pulmonary inflammation and improve survival, but the recommended 21-day duration is based on limited historical evidence. Prolonged corticosteroid exposure may increase risks including secondary infections, hyperglycemia, gastrointestinal bleeding, and other adverse effects. The HOW LONG trial tests whether stopping corticosteroids earlier, after clinical recovery, improves net clinical outcomes.
Eligible adults with proven or probable severe PCP who have recovered to room air (no need for supplemental oxygen) for at least 6 hours by day 10 of corticosteroid therapy are enrolled and randomized centrally 1:1 in the MUHC Research Electronic Data Capture (REDCap) system to (1) discontinuation of corticosteroids at day 10 or hospital discharge or (2) continuation of corticosteroids to a total of 21 days. All participants receive standard antimicrobial therapy for PCP per treating clinicians. Follow-up occurs to day 180.
The primary endpoint is a hierarchical composite outcome assessed at day 60, incorporating mortality, relapse of PCP-related hypoxemia, secondary infections, severe metabolic or gastrointestinal complications, and length of hospital stay. Secondary endpoints include individual components of the composite outcome, and tertiary endpoints include quality of life and longer-term outcomes through day 180.
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
- None
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
- •Age ≥18 years
- •Proven or probable Pneumocystis jirovecii pneumonia
- •Severe PCP requiring supplemental oxygen (e.g., ≥4 L/min or ≥35% FiO₂ to maintain SpO₂ ≥94%)
- •Planned or receiving adjunctive systemic corticosteroid therapy for severe PCP
- •Clinical recovery by day 10 of steroid therapy: breathing room air for ≥6 hours
- •Able to provide informed consent (or per local requirements)
排除标准
- •Persistent hypoxemia or ongoing oxygen requirement at day 10
- •Clinical deterioration prior to randomization
- •Treating clinician determines steroids must be continued or stopped immediately for medical reasons
- •Anticipated death within 48 hours
- •Inability or unwillingness to complete follow-up through day 180
研究组 & 干预措施
Shortened-Duration Corticosteroids
Discontinue adjunctive systemic corticosteroids at day 10 of therapy or at hospital discharge (whichever occurs first), after documented clinical recovery (room air for ≥6 hours).
干预措施: Systemic corticosteroids (Drug)
Standard duration of Corticosteroids
Continue adjunctive systemic corticosteroids to a total of 21 days (standard of care).
干预措施: Systemic corticosteroids (Drug)
结局指标
主要结局
Hierarchical composite clinical outcome
时间窗: Day 60
The primary outcome at day 60 will be the hierarchical composite of: 1. death, 2. relapse of PCP-related hypoxemia (e.g., not due to another obviously identified cause like pulmonary embolism, aspiration event, etc.) requiring more than 12 hours of use of ≥2L of oxygen in accordance with guidelines 3. The development of secondary infections requiring systemic antibiotic therapy 4. The development of severe diabetic complications (ketoacidosis, hyperosmolar coma, new initiation of insulin which is continued at discharge) 5. The development of severe GI bleeding (e.g., necessitating unplanned transfusion and/or endoscopy) and; 6. inpatient length of stay (censored at day 60; deaths assigned 60 days).
次要结局
- Death(Day 60)
- relapse of PCP-related hypoxemia(Day 60)
- Secondary infections requiring systemic antibiotic therapy(Day 60)
- The development of severe diabetic complications(Day 60)
- The development of severe GI bleeding ((Day 60)
- inpatient length of stay (censored at day 60; deaths assigned 60 days).(Day 60)
研究者
Emily McDonald
Associate professor of medicine
McGill University Health Centre/Research Institute of the McGill University Health Centre