Invasive Pulmonary AspergillosisPhase 1NAIFI01NCT04267497
Nebulised Liposomal Amphotericin for Invasive Pulmonary Aspergillosis (NAIFI01 Study)
A Phase 1 study testing Amphotericin B Liposomal 50 MG in people with Invasive Pulmonary Aspergillosis, run by Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal at 1 site in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Invasive Pulmonary Aspergillosis
- What is being tested?
- Amphotericin B Liposomal 50 MG
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 13 participants
- Where
- 1 siteSpain
- Study dates
- 18 Oct 2019to 10 Nov 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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);
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I, Prospective, Randomised, Controlled Study on the Safety and Efficacy of Nebulised Liposomal Amphotericin as an Adjuvant Treatment for Invasive Pulmonary Aspergillosis
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).
Read the 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
- Being tested
- Amphotericin B Liposomal 50 MG, Placebo
- Medical subject headings
- Invasive Pulmonary Aspergillosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Amphotericin B Liposomal 50 MGDrug
Also called Ambisome
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.
PlaceboOther
Sterile water for injection. It will be administered by nebulized route: 6 ml, 3 times a week for 6 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Nebulized Amphotericin B | Experimental | Amphotericin B. Receives: Drug: Amphotericin B Liposomal 50 MG |
| Nebulized Placebo | Placebo comparator | Sterile water for injection. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: During amphotericin treatment: week 1 to week 6
Secondary outcomes (7)
Fr Resp/min (Breathing rate per minute)
Change in Fr Resp/min values postnebulization compared to values before nebulization
Measured: During amphotericin treatment: week 1 to week 6
Sat 02 (%) (Percentage of oxygen saturation)
Change in Sat 02 (%) values postnebulization compared to values before nebulization
Measured: During amphotericin treatment: week 1 to week 6
Fr Card/min (Heart rate per minute)
Change in Card/min values postnebulization compared to values before nebulization
Measured: During amphotericin treatment: week 1 to week 6
Number of events observed at pulmonary level.
Symptomatic cough, bronchospasm (auscultation), dyspnea or shortness of breath, need for bronchodilator treatment.
Measured: During amphotericin treatment: week 1 to week 6
Pharmacokinetics. Concentrations of amphotericin
Amphotericin concentrations in bronchoalveolar lavage and in plasma.
Measured: Week 6
Radiological response
Evaluated by PET-TC
Measured: Week 6
Microbiological response.
Evaluated in bronchoalveolar lavage (BAL)
Measured: Week 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2020
- Study start18 Oct 2019
- Primary completion10 Nov 2022
- Study completion10 Nov 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Invasive Pulmonary AspergillosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Phase I, One-center, Prospective, Randomized and controlled study
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sonsoles Sancho, Study chair, President of CEIC Hospital Ramon y Cajal
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04267497
- Sponsor's protocol ID
- FundacionRamonCajal
- Acronym
- NAIFI01
- Status last verified
- Jan 2021
- First submitted
- 24 Dec 2019
- Last updated
- 15 Jun 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Identifiing candidates prospectively according inclusion and exclusion criteria
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I, Prospective, Randomised, Controlled Study on the Safety and Efficacy of Nebulised Liposomal Amphotericin as an Adjuvant Treatment for Invasive Pulmonary Aspergillosis
- ClinicalTrials.gov ID
- NCT04267497
- Acronym / sponsor ID
- NAIFI01 / FundacionRamonCajal
- Conditions
- Invasive Pulmonary Aspergillosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y CajalUniversity, hospital or other
- Study start
- 18 Oct 2019 (actual)
- Primary completion
- 10 Nov 2022 (actual)
- Study completion
- 10 Nov 2022 (actual)
- First posted
- 13 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- Phase I, One-center, Prospective, Randomized and controlled study
| Arm | Type | Receives |
|---|---|---|
| Nebulized Amphotericin B | Experimental | Drug: Amphotericin B Liposomal 50 MGAmphotericin B. |
| Nebulized Placebo | Placebo comparator | Other: PlaceboSterile water for injection. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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:
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Amphotericin B Liposomal 50 MGAlso: AmbisomeAmphotericin 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. | Drug | Nebulized Amphotericin B |
| PlaceboSterile water for injection. It will be administered by nebulized route: 6 ml, 3 times a week for 6 weeks. | Other | Nebulized Placebo |
Primary outcome
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.
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.
7 secondary outcomes
Fr Resp/min (Breathing rate per minute)
Time frame: During amphotericin treatment: week 1 to week 6
Sat 02 (%) (Percentage of oxygen saturation)
Time frame: 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
Number of events observed at pulmonary level.
Time frame: During amphotericin treatment: week 1 to week 6
Pharmacokinetics. Concentrations of amphotericin
Time frame: Week 6
Radiological response
Time frame: Week 6
Microbiological response.
Time frame: Week 6
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2023.
- Individual participant dataSharing planned: Yes. Identifiing candidates prospectively according inclusion and exclusion criteria
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sonsoles Sancho study chair
President of CEIC Hospital Ramon y Cajal
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Amphotericin B Liposomal 50 MG in people with Invasive Pulmonary Aspergillosis, run by Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Reduction of >20% of FVC postnebulization compared to values before amphotericin nebulization (time frame: During amphotericin treatment: week 1 to week 6). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2023.