- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04267497
Nebulised Liposomal Amphotericin for Invasive Pulmonary Aspergillosis (NAIFI01 Study) (NAIFI01)
Phase I, Prospective, Randomised, Controlled Study on the Safety and Efficacy of Nebulised Liposomal Amphotericin as an Adjuvant Treatment for Invasive Pulmonary Aspergillosis
Study Overview
Status
Conditions
Intervention / Treatment
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
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Jesus Fortun, PhD
- Phone Number: 8710 +34913368000
- Email: fortunabete@gmail.com
Study Contact Backup
- Name: Maria A Galvez
- Phone Number: 8825 +34913368000
- Email: mariaangeles.galvez@salud.madrid.org
Study Locations
-
-
-
Madrid, Spain, 28760
- Jesus Fortun
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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);
Exclusion Criteria:
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Nebulized Amphotericin B
Amphotericin B.
|
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 Names:
|
Placebo Comparator: Nebulized Placebo
Sterile water for injection.
|
Sterile water for injection.
It will be administered by nebulized route: 6 ml, 3 times a week for 6 weeks.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Reduction of >20% of FVC postnebulization compared to values before amphotericin nebulization
Time Frame: 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.
|
During amphotericin treatment: week 1 to week 6
|
Reduction of >20% of FEV1 postnebulization compared to values before amphotericin nebulization
Time Frame: 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.
|
During amphotericin treatment: week 1 to week 6
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Fr Resp/min (Breathing rate per minute)
Time Frame: During amphotericin treatment: week 1 to week 6
|
Change in Fr Resp/min values postnebulization compared to values before nebulization
|
During amphotericin treatment: week 1 to week 6
|
Sat 02 (%) (Percentage of oxygen saturation)
Time Frame: During amphotericin treatment: week 1 to week 6
|
Change in Sat 02 (%) values postnebulization compared to values before nebulization
|
During amphotericin treatment: week 1 to week 6
|
Fr Card/min (Heart rate per minute)
Time Frame: During amphotericin treatment: week 1 to week 6
|
Change in Card/min values postnebulization compared to values before nebulization
|
During amphotericin treatment: week 1 to week 6
|
Number of events observed at pulmonary level.
Time Frame: During amphotericin treatment: week 1 to week 6
|
Symptomatic cough, bronchospasm (auscultation), dyspnea or shortness of breath, need for bronchodilator treatment.
|
During amphotericin treatment: week 1 to week 6
|
Pharmacokinetics. Concentrations of amphotericin
Time Frame: Week 6
|
Amphotericin concentrations in bronchoalveolar lavage and in plasma.
|
Week 6
|
Radiological response
Time Frame: Week 6
|
Evaluated by PET-TC
|
Week 6
|
Microbiological response.
Time Frame: Week 6
|
Evaluated in bronchoalveolar lavage (BAL)
|
Week 6
|
Collaborators and Investigators
Investigators
- Study Chair: Sonsoles Sancho, President of CEIC Hospital Ramon y Cajal
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Infections
- Respiratory Tract Diseases
- Lung Diseases
- Bacterial Infections and Mycoses
- Mycoses
- Invasive Fungal Infections
- Lung Diseases, Fungal
- Aspergillosis
- Pulmonary Aspergillosis
- Invasive Pulmonary Aspergillosis
- Anti-Infective Agents
- Anti-Bacterial Agents
- Antifungal Agents
- Antiprotozoal Agents
- Antiparasitic Agents
- Amebicides
- Amphotericin B
- Liposomal amphotericin B
Other Study ID Numbers
- FundacionRamonCajal
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
- ANALYTIC_CODE
- CSR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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