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

Poitiers University Hospital

Status and phase: Completed; Phase 2

Conditions: Allergic Bronchopulmonary Aspergillosis

Treatments: Drug: placebo; Drug: Liposomal amphotericin B (Ambisome®)

Study type: Interventional

Funder types: Other

Identifiers

NCT02273661

NEBULAMB

Details and patient eligibility

About

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.

Enrollment: 174 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

All patients with ABPA justifying an attack treatment with corticosteroids and itraconazole and combining the following criteria:

1. 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.
2. 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.
3. 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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174 participants in 2 patient groups, including a placebo group

Control

Placebo Comparator group

Description:

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

Treatment:

Drug: placebo

Ambisome

Experimental group

Description:

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

Treatment:

Drug: Liposomal amphotericin B (Ambisome®)