NCT04267497

Nebulised Liposomal Amphotericin for Invasive Pulmonary Aspergillosis (NAIFI01 Study)

Phase I, Prospective, Randomised, Controlled Study on the Safety and Efficacy of Nebulised Liposomal Amphotericin as an Adjuvant Treatment for Invasive Pulmonary Aspergillosis

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 13 (actual)
• Sponsor: Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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).

Detailed description

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. In each visit made during the nebulized therapy period (week 1 visit in view of week 6) the following parameters will be objectified: before and after nebulization: * forced vital capacity (FVC) * forced expiration volume in 1 second (FEV1) Both parameters will be measured with the Micro Spirometer; Micro Medical Ltd; Rochester UK). Repeat 3 times and obtain the higher value Secondary variables: * Related to tolerability and safety * At systemic level: Fr Resp/min: Breathing rate per minute, Fr Card/min: Heart rate per minute, BP (mmHg): Systolic and diastolic blood pressure, Sat 02 (%): Percentage of oxygen saturation (digital pulse oximetry), blood test disturbances. * At the pulmonary level: symptomatic cough, bronchospasm (auscultation), dyspnea or shortness of breath, need for bronchodilator treatment. * Others: bad taste in mouth, nausea, dysphagia Given the practical absence of systemic passage of nebulized Ambisome confirmed in other studies, the practical absence of reported systemic reactions and given the high number of systemic events that these patients develop in relation to their underlying pathology and the use of other systemic treatments, adverse events of an extrapulmonary or systemic nature that are not considered adverse reactions (related to nebulized therapy, the object of the study) will not be collected for the study. * related to pharmacokinetics * Concentration of amphotericin in bronchoalveolar lavage * Plasma amphotericin concentration Related to Effectiveness * Radiological efficacy (including PET-CT control): Image response and PET-CT performance: Quantification of SUV metabolic uptake index in a combined positron emission tomography (PET-CT). * Microbiological efficacy in BAL: Microbiological response in bronchoalveolar lavage (BAL): Comparison of results of calcofluor staining, fungal culture, galactomannan, BDGlucan and Aspergillus PCR of BAL samples obtained by fibrobronchoscopy * Serum microbiological response: Comparison of results for galactomannan and BDGlucan in serum during the weeks of study follow-up

Conditions

• Invasive Pulmonary Aspergillosis

Interventions

Type	Name	Description
DRUG	Amphotericin B Liposomal 50 MG	Amphotericin B 50 mg powder for infusion diluted in 12 ml of sterile water. It will be administered by nebulized route 25 mg (6 ml), 3 times a week, for 6 weeks.
OTHER	Placebo	Sterile water for injection. It will be administered by nebulized route: 6 ml, 3 times a week for 6 weeks.

Timeline

• Start date: 2019-10-18
• Primary completion: 2022-11-10
• Completion: 2022-11-10
• First posted: 2020-02-13
• Last updated: 2023-06-15

Locations

1 site across 1 country: Spain