Evaluation of a Therapeutic Strategy Including Nebulised Liposomal Amphotericin B (Ambisome®) in Maintenance Treatment of Allergic Bronchopulmonary Aspergillosis (Cystic Fibrosis Excluded). (NEBULAMB)
Primary Purpose
Allergic Bronchopulmonary Aspergillosis
Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Liposomal amphotericin B (Ambisome®)
placebo
Sponsored by
About this trial
This is an interventional treatment trial for Allergic Bronchopulmonary Aspergillosis
Eligibility Criteria
Inclusion Criteria:
All patients with ABPA justifying an attack treatment with corticosteroids and itraconazole and combining the following criteria:
- atopic subject or a history of asthma , history of total Immunoglobin E (IgE)> 417 kU / L (or > 210 kU / L with a clear worsening) of a known ABPA), specific Immunoglobin E against Aspergillus fumigatus positive ( >0.35 KUA/L) or positive skin tests.
- associated with two other of the following criteria: documentation of precipitating antibodies or Immunoglobulin G positive to Aspergillus fumigatus, of radiological infiltrates associated with ABPA (transitional / persistent / bronchial dilation), of blood eosinophilia > 500 elements/mm3.
- After informing and obtaining consent signed.
Exclusion Criteria:
- Women of childbearing age who do not have an effective contraception for at least 12 first months of the study( 10 months + 2 months of treatment washout) pregnant or lactating women,
- Patient with cystic fibrosis
- Patient with a contra-indication to itraconazole
- Intolerance to β2 -agonists
- Known hypersensitivity to liposomal amphotericin B or any other component
- Laboratory abnormalities: significant abnormalities of platelet blood count , liver function tests (SGPT, SGOT(serum glutamate oxaloacetate transaminase) , total bilirubin > 5 times the upper limit of the normal range )
- severe renal function impairment (creatinine clearance enf to 30 ml/min)
- Concomitant use of one or more of the following treatments: Alfuzosine, alcaloïdes de l'ergot de seigle vasoconstricteur, aliskiren, astemizole, atorvastatine, avanafil, association Ombitasvir and Paritaprevir, Bepridil, Cisaprid, Dabigatran, dapoxetin, domperidon, dronedaron, Eplerenone, Halofantrin, Ivabradin, Lomitapid, lurasidon, Millepertuis, mizolastin, Pimozid,Quétiapin, quinidin, Ranolazine, ritonavir, Sertindole, sildénafil, simvastatin, sirolimus, Sultoprid, Terfenadine, ticagrelor, triazolam Vardénafil (in men over than 75)
- patient with anti IgE- monoclonal antibody for less than 4 months or with current complications related to previous treatment with anti IgE- monoclonal antibody -
- Ventricular dysfunction demonstrated such as congestive heart failure or a history of congestive heart failure
- Simple aspergilloma, chronic pulmonary aspergillosis, invasive pulmonary aspergillosis
- Respiratory infection aggravating asthma or ABPA
Sites / Locations
- Chu de Poitiers
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Control
Ambisome
Arm Description
An aerosol of isotonic saline x 1/ week will be administered during 6 months
An aerosol of Liposomal Amphotericin B (Ambisome®) at 25 mg x 1/ week will be administered during 6 months
Outcomes
Primary Outcome Measures
occurrence of first severe clinical exacerbation
Occurrence of severe clinical exacerbation within 24 months following attack treatment, defined by the onset or worsening of dyspnea aggravating the baseline condition that justified:
-increased inhalation treatments (inhaled bronchodilators and / or corticosteroids)
and / or initiation of systemic corticosteroid treatment
and / or hospitalization
AND persisting for more than 7 days.
Secondary Outcome Measures
Full Information
NCT ID
NCT02273661
First Posted
October 22, 2014
Last Updated
June 8, 2020
Sponsor
Poitiers University Hospital
1. Study Identification
Unique Protocol Identification Number
NCT02273661
Brief Title
Evaluation of a Therapeutic Strategy Including Nebulised Liposomal Amphotericin B (Ambisome®) in Maintenance Treatment of Allergic Bronchopulmonary Aspergillosis (Cystic Fibrosis Excluded).
Acronym
NEBULAMB
Official Title
Evaluation of a Therapeutic Strategy Including Nebulised Liposomal Amphotericin B (Ambisome®) in Maintenance Treatment of Allergic Bronchopulmonary Aspergillosis (Cystic Fibrosis Excluded)
Study Type
Interventional
2. Study Status
Record Verification Date
June 2020
Overall Recruitment Status
Completed
Study Start Date
November 19, 2014 (Actual)
Primary Completion Date
June 28, 2019 (Actual)
Study Completion Date
June 28, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Poitiers University Hospital
4. Oversight
5. Study Description
Brief Summary
Compare the incidence of severe clinical exacerbations in the treatment of ABPA, between a strategy with a maintenance treatment and a conventional strategy without antifungal maintenance therapy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Allergic Bronchopulmonary Aspergillosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
174 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Control
Arm Type
Placebo Comparator
Arm Description
An aerosol of isotonic saline x 1/ week will be administered during 6 months
Arm Title
Ambisome
Arm Type
Experimental
Arm Description
An aerosol of Liposomal Amphotericin B (Ambisome®) at 25 mg x 1/ week will be administered during 6 months
Intervention Type
Drug
Intervention Name(s)
Liposomal amphotericin B (Ambisome®)
Intervention Description
An aerosol of Liposomal Amphotericin B (Ambisome®) at 25 mg x 1/ week will be administered during 6 months
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
An aerosol of isotonic saline x 1/ week will be administered during 6 months
Primary Outcome Measure Information:
Title
occurrence of first severe clinical exacerbation
Description
Occurrence of severe clinical exacerbation within 24 months following attack treatment, defined by the onset or worsening of dyspnea aggravating the baseline condition that justified:
-increased inhalation treatments (inhaled bronchodilators and / or corticosteroids)
and / or initiation of systemic corticosteroid treatment
and / or hospitalization
AND persisting for more than 7 days.
Time Frame
within 24 months following the attack treatment,
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
All patients with ABPA justifying an attack treatment with corticosteroids and itraconazole and combining the following criteria:
atopic subject or a history of asthma , history of total Immunoglobin E (IgE)> 417 kU / L (or > 210 kU / L with a clear worsening) of a known ABPA), specific Immunoglobin E against Aspergillus fumigatus positive ( >0.35 KUA/L) or positive skin tests.
associated with two other of the following criteria: documentation of precipitating antibodies or Immunoglobulin G positive to Aspergillus fumigatus, of radiological infiltrates associated with ABPA (transitional / persistent / bronchial dilation), of blood eosinophilia > 500 elements/mm3.
After informing and obtaining consent signed.
Exclusion Criteria:
Women of childbearing age who do not have an effective contraception for at least 12 first months of the study( 10 months + 2 months of treatment washout) pregnant or lactating women,
Patient with cystic fibrosis
Patient with a contra-indication to itraconazole
Intolerance to β2 -agonists
Known hypersensitivity to liposomal amphotericin B or any other component
Laboratory abnormalities: significant abnormalities of platelet blood count , liver function tests (SGPT, SGOT(serum glutamate oxaloacetate transaminase) , total bilirubin > 5 times the upper limit of the normal range )
severe renal function impairment (creatinine clearance enf to 30 ml/min)
Concomitant use of one or more of the following treatments: Alfuzosine, alcaloïdes de l'ergot de seigle vasoconstricteur, aliskiren, astemizole, atorvastatine, avanafil, association Ombitasvir and Paritaprevir, Bepridil, Cisaprid, Dabigatran, dapoxetin, domperidon, dronedaron, Eplerenone, Halofantrin, Ivabradin, Lomitapid, lurasidon, Millepertuis, mizolastin, Pimozid,Quétiapin, quinidin, Ranolazine, ritonavir, Sertindole, sildénafil, simvastatin, sirolimus, Sultoprid, Terfenadine, ticagrelor, triazolam Vardénafil (in men over than 75)
patient with anti IgE- monoclonal antibody for less than 4 months or with current complications related to previous treatment with anti IgE- monoclonal antibody -
Ventricular dysfunction demonstrated such as congestive heart failure or a history of congestive heart failure
Simple aspergilloma, chronic pulmonary aspergillosis, invasive pulmonary aspergillosis
Respiratory infection aggravating asthma or ABPA
Facility Information:
Facility Name
Chu de Poitiers
City
Poitiers
ZIP/Postal Code
86000
Country
France
12. IPD Sharing Statement
Citations:
PubMed Identifier
34764182
Citation
Godet C, Couturaud F, Marchand-Adam S, Pison C, Gagnadoux F, Blanchard E, Taille C, Philippe B, Hirschi S, Andrejak C, Bourdin A, Chenivesse C, Dominique S, Bassinet L, Murris-Espin M, Riviere F, Garcia G, Caillaud D, Blanc FX, Goupil F, Bergeron A, Gondouin A, Frat JP, Flament T, Camara B, Priou P, Brun AL, Laurent F, Ragot S, Cadranel J; NebuLamB study group and GREPI network; Godet C, Couturaud F, Cadranel J, Frat JP, Brun AL, Laurent F, Marchand-Adam S, Pison C, Gagnadoux F, Blanchard E, Taille C, Philippe B, Hirschi S, Andrejak C, Chenivesse C, Dominique S, Bassinet L, Murris-Espin M, Riviere F, Garcia G, Caillaud D, Blanc FX, Goupil F, Gondouin A, Flament T, Camara B, Priou P, Ragot S. Nebulised liposomal amphotericin-B as maintenance therapy in allergic bronchopulmonary aspergillosis: a randomised, multicentre trial. Eur Respir J. 2022 Jun 16;59(6):2102218. doi: 10.1183/13993003.02218-2021. Print 2022 Jun.
Results Reference
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Evaluation of a Therapeutic Strategy Including Nebulised Liposomal Amphotericin B (Ambisome®) in Maintenance Treatment of Allergic Bronchopulmonary Aspergillosis (Cystic Fibrosis Excluded).
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