NEBULAMB: Evaluation of a Therapeutic Strategy Including Nebulised Liposomal Amphotericin B (Ambisome®) in Maintenance Treatment of Allergic Bronchopulmonary Aspergillosis (Cystic Fibrosis Excluded).

Sponsor

Poitiers University Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT02273661

Collaborator

(none)

174

Enrollment

Location

Arms

55.3

Actual Duration (Months)

3.1

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Allergic Bronchopulmonary Aspergillosis	Drug: Liposomal amphotericin B (Ambisome®) Drug: placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

174 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Treatment

Official Title:

Evaluation of a Therapeutic Strategy Including Nebulised Liposomal Amphotericin B (Ambisome®) in Maintenance Treatment of Allergic Bronchopulmonary Aspergillosis (Cystic Fibrosis Excluded)

Actual Study Start Date :

Nov 19, 2014

Actual Primary Completion Date :

Jun 28, 2019

Actual Study Completion Date :

Jun 28, 2019

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Control An aerosol of isotonic saline x 1/ week will be administered during 6 months	Drug: placebo An aerosol of isotonic saline x 1/ week will be administered during 6 months
Experimental: Ambisome An aerosol of Liposomal Amphotericin B (Ambisome®) at 25 mg x 1/ week will be administered during 6 months	Drug: Liposomal amphotericin B (Ambisome®) An aerosol of Liposomal Amphotericin B (Ambisome®) at 25 mg x 1/ week will be administered during 6 months

Arm

Intervention/Treatment

Placebo Comparator: Control

An aerosol of isotonic saline x 1/ week will be administered during 6 months

Drug: placebo

An aerosol of isotonic saline x 1/ week will be administered during 6 months

Experimental: Ambisome

An aerosol of Liposomal Amphotericin B (Ambisome®) at 25 mg x 1/ week will be administered during 6 months

Drug: Liposomal amphotericin B (Ambisome®)

An aerosol of Liposomal Amphotericin B (Ambisome®) at 25 mg x 1/ week will be administered during 6 months

Outcome Measures

Primary Outcome Measures

occurrence of first severe clinical exacerbation [within 24 months following the attack treatment,]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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