A Randomized Controlled Trial of Amphotericin B Versus Posaconazole for Treating Pulmonary Mucormycosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 82
- 试验地点
- 2
- 主要终点
- The proportion of participants achieving a successful outcome (complete response or partial response) at the completion of six weeks. The response assessment will be a composite of clinical and radiological as adjudged by a multidisciplinary team
研究概览
简要总结
Pulmonary mucormycosis is a serious illness with high morbidity and mortality (approximately 57%). Surgery and antifungal therapy are central in the management of mucormycosis. Unlike rhino-orbital mucormycosis, surgery is not feasible in several patients with pulmonary mucormycosis. Hence, treatment is primarily with antifungal therapy. Amphotericin B is the standard of care in the medical management of mucormycosis. However, amphotericin B is expensive, has significant adverse events, and is available only in parenteral formulation. Posaconazole is effective against Mucorales, and is currently approved for salvage therapy of mucormycosis. Recent evidence suggest that in several patients, posaconazole may be effective as a monotherapy upfront. In the current study posaconazole versus amphotericin B will be evaluated for the management of pulmonary mucormycosis in a randomized clinical trial.
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
- Double (Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 13 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects with proven or probable pulmonary mucormycosis. Participants with a suspicion of pulmonary mucormycosis (as defined previously) based on compatible clinical presentation and compatible imaging will be screened for inclusion in the study.
排除标准
- •Failure to provide informed consent
- •Contraindications or hypersensitivity to amphotericin B, posaconazole or their components
- •Already received >4 days of antifungals prior to randomization into the study
- •Pregnant women
- •High chances of mortality within 48 hours of enrolment into the study
- •Subjects with possible pulmonary mucormycosis will also be excluded, if their diagnosis is not confirmed within four working days of enrollment
研究组 & 干预措施
Posaconazole arm
Combination of liposomal amphotericin B (5 mg/kg per day) and posaconazole for first 7 days followed by oral posaconazole only (for induction as well as maintenance therapy). The first four weeks of therapy will be called induction therapy
干预措施: Liposomal Amphotericin B (Drug)
Amphotericin B arm (standard of care)
Intravenous liposomal amphotericin B [5 mg/kg per day] for at least 4 weeks followed by maintenance therapy. Maintenance therapy (after four weeks of treatment initiation) will be continued for at least 12 weeks or longer as decided by the treating physician. The maintenance therapy will be posaconazole. However, if therapeutic drug monitoring is not possible or the participants opt to use isavuconazole or amphotericin, the same will be permitted and noted
干预措施: Liposomal Amphotericin B (Drug)
Posaconazole arm
Combination of liposomal amphotericin B (5 mg/kg per day) and posaconazole for first 7 days followed by oral posaconazole only (for induction as well as maintenance therapy). The first four weeks of therapy will be called induction therapy
干预措施: Posaconazole 600 mg followed by posaconazole 300 mg once daily (Drug)
结局指标
主要结局
The proportion of participants achieving a successful outcome (complete response or partial response) at the completion of six weeks. The response assessment will be a composite of clinical and radiological as adjudged by a multidisciplinary team
时间窗: six weeks after randomization
Overall response based on clinical assessment at six weeks after randomization as described recently in a Delphi consensus statement and previous studies on invasive mold infection of the lung. (PMID: 35390293) Based on clinical and radiological response (assessed on CT scan using the two-dimensional measurement of the largest target lesion \[WHO criteria, like in lung cancer response assessment\]). The overall response will be classified as complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD) or death. CR or PR will be labeled success, while SD, PD or death will be labeled as failure
次要结局
- The proportion of participants achieving a successful outcome (complete response or partial response) at the completion of twelve weeks. The response assessment will be a composite of clinical and radiological as adjudged by a multidisciplinary team(telve weeks after randomization)
- 90-day mortality(90 days after randomization)
- Adverse events related to therapy and the number of participants needing either discontinuation or modification of drug therapy due to adverse events(First four weeks of randomization)
研究者
Ritesh Agarwal
Professor
Post Graduate Institute of Medical Education and Research, Chandigarh