Nebulised Liposomal Amphotericin for Invasive Pulmonary Aspergillosis (NAIFI01 Study)

NCT04267497 | Completed Phase 1 DMC

• 1 other identifier: FundacionRamonCajal
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Invasive Pulmonary Aspergillosis

Outcome Measures

Primary Outcomes (2)

• Reduction of >20% of FVC postnebulization compared to values before amphotericin nebulization

  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.

  During amphotericin treatment: week 1 to week 6

• Reduction of >20% of FEV1 postnebulization compared to values before amphotericin nebulization

  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.

  During amphotericin treatment: week 1 to week 6

Secondary Outcomes (7)

• 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

• Fr Card/min (Heart rate per minute)

  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

Study Arms (2)

Nebulized Amphotericin B

EXPERIMENTAL

Amphotericin B.

Drug: Amphotericin B Liposomal 50 MG

Nebulized Placebo

PLACEBO COMPARATOR

Sterile water for injection.

Other: Placebo

Interventions

Amphotericin B Liposomal 50 MG DRUG

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.

Also known as: Ambisome

Nebulized Amphotericin B

Placebo OTHER

Sterile water for injection. It will be administered by nebulized route: 6 ml, 3 times a week for 6 weeks.

Nebulized Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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);

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal: lead

Study Sites (1)

Jesus Fortun

Madrid, 28760, Spain

Location

MeSH Terms

Conditions

Invasive Pulmonary Aspergillosis

Interventions

Amphotericin B; liposomal amphotericin B

Condition Hierarchy (Ancestors)

Pulmonary Aspergillosis; Aspergillosis; Mycoses; Bacterial Infections and Mycoses; Infections; Invasive Fungal Infections; Lung Diseases, Fungal; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Polyketides; Lactones; Organic Chemicals

Study Officials

• Sonsoles Sancho

  President of CEIC Hospital Ramon y Cajal

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase I, One-center, Prospective, Randomized and controlled study

Study Record Dates

• First Submitted: December 24, 2019
• First Posted: February 13, 2020
• Study Start: October 18, 2019
• Primary Completion: November 10, 2022
• Study Completion: November 10, 2022
• Last Updated: June 15, 2023

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Data will be available whiting 6 month of study completion

Locations

ES (1)