Phase I, Prospective, Randomised, Controlled Study on the Safety and Efficacy of Nebulised Liposomal Amphotericin as an Adjuvant Treatment for Invasive Pulmonary Aspergillosis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- Reduction of >20% of FVC postnebulization compared to values before amphotericin nebulization
研究概览
简要总结
The investigators aim to assess the safety and efficacy of nebulized liposomal amphotericin B (ALN) as a complementary therapy to the usual systemic treatment in patients with invasive pulmonary aspergillosis and the utility of a non-routine test as a surrogate marker of efficacy. To this end, a 3-year phase I, prospective, randomized and controlled clinical trial will be carried out in a single center, in patients with proven or probable pulmonary aspergillosis receiving routine systemic treatment. Participants will be randomized ( 1: 1) to receive ALN, 25 mg or nebulizer injection water 3 times a week, for 6 weeks. The primary objective is the safety of ALN in this scenario, including clinical tolerance and pharmacokinetic studies. Secondary objectives are presented as: a) clinical efficacy, using the following criteria: complete response, partial response, stability and progression or death, on week 12; b) microbiological efficacy, using culture, galactomannan, BDGlucan and Aspergillus PCR in induced sputum on week +6; and c) to explore the utility of the SUV ("standardized uptake value") index in PET-CT performed on week +6 in relation to a baseline PET-CT as a surrogate marker of response. The administration of ALN and placebo will be carried out by eFlowR vibrating membrane electronic nebulizers. To carry out the study, the following visits will be made: baseline, week 1,2,3,4,5,6 (efficacy and safety evaluation), 9 and 12 (overall evaluation).
详细描述
Phase of the clinical trial Phase I trial (pilot study), prospective, randomised, controlled trial using a drug under conditions of use not approved for the form of administration.
It is a Phase I study since the primary objective includes tolerance analysis, safety and pharmacokinetic and distribution studies of nebulized amphotericin, but when administered to patients it also carries out the preliminary assessment of the safety and efficacy of the treatment.
Primary and secondary variables
Primary variable:
Reduction of >20% of post-nebulized FVC and FEV1 in relation to values obtained before nebulization.
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
- Single (Participant)
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
- •Those over 18 years of age, signed by the IC or its representative, with a compatible respiratory clinic and meeting the following criteria will be included in the study: aspergillosis confirmed in sterile sample culture (e.g. lung biopsy) or with histological evidence of invasion, regardless of the patient's condition (proven aspergillosis).
- •In the absence of proven aspergillosis, patients who meet all 3 conditions below are considered likely and also eligible for inclusion:
- •Clinical criteria: neutropenia (<500 neutrophils /ul), haematological malignancy, haematopoietic parent transplantation, solid organ transplantation, prolonged use of steroids, solid tumour, HIV infection, systemic diseases requiring immunosuppressive therapy, chronic obstructive pulmonary disease, cirrhosis, malnutrition, post-operative cardiac surgery or respiratory distress secondary to influenza;
- •Radiological criteria (TAC): infiltrates with halo effect, aerial meniscus, nodular, cavitated, ground glass, tree in bud or in general the presence of abnormal or persistent images refractory to antibiotherapy;
- •Microbiological criterion: isolation of Aspergillus spp in respiratory samples (whether or not associated with hyphae vision in staining techniques) or the positivity of galactomannan in serum (>0.5 x2 or >0.8 x1) or galactomannan in BAL (>1.0);
排除标准
- •Inability or refusal of the patient (or his/her legal representative) to grant the IC.
- •Pregnancy or planning to become pregnant during the course of the study. Breastfeeding.
- •Formal contraindication for the administration of nebulized drugs, hypersensitivity to amphotericin.
- •Patients admitted to the ICU and patients who at the time of randomization are intubated or require imminent intubation cannot be included because some studies have confirmed that nebulized Ambisome can precipitate in the breathing tubes.
- •Participation in another clinical trial in the previous month or life expectancy < 1 week.
研究组 & 干预措施
Nebulized Amphotericin B
Amphotericin B.
干预措施: Amphotericin B Liposomal 50 MG (Drug)
Nebulized Placebo
Sterile water for injection.
干预措施: Placebo (Other)
结局指标
主要结局
Reduction of >20% of FVC postnebulization compared to values before amphotericin nebulization
时间窗: During amphotericin treatment: week 1 to week 6
FVC will be measured with the Micro Spirometer (Micro Medical Ltd; Rochester UK) 3 times before and after nebulization and the higher value will be recorded.
Reduction of >20% of FEV1 postnebulization compared to values before amphotericin nebulization
时间窗: During amphotericin treatment: week 1 to week 6
FEV1 will be measured with the Micro Spirometer (Micro Medical Ltd; Rochester UK) 3 times before and after nebulization and the higher value will be recorded.
次要结局
- Fr Card/min (Heart rate per minute)(During amphotericin treatment: week 1 to week 6)
- Microbiological response.(Week 6)
- Fr Resp/min (Breathing rate per minute)(During amphotericin treatment: week 1 to week 6)
- Sat 02 (%) (Percentage of oxygen saturation)(During amphotericin treatment: week 1 to week 6)
- Number of events observed at pulmonary level.(During amphotericin treatment: week 1 to week 6)
- Pharmacokinetics. Concentrations of amphotericin(Week 6)
- Radiological response(Week 6)