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

NCT02273661 | Completed Phase 2

• 1 other identifier: NEBULAMB
• Study Type: interventional
• Target: 174
• Locations: 1 country
• Sites: 1

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.

Conditions

Allergic Bronchopulmonary Aspergillosis

Outcome Measures

Primary Outcomes (1)

• 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: 1. -increased inhalation treatments (inhaled bronchodilators and / or corticosteroids) * and / or initiation of systemic corticosteroid treatment * and / or hospitalization 2. AND persisting for more than 7 days.

  within 24 months following the attack treatment,

Study Arms (2)

Control

PLACEBO COMPARATOR

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

Drug: placebo

Ambisome

EXPERIMENTAL

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

Drug: Liposomal amphotericin B (Ambisome®)

Interventions

Liposomal amphotericin B (Ambisome®) DRUG

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

Ambisome

placebo DRUG

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

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Poitiers University Hospital: lead

Study Sites (1)

Chu de Poitiers

Poitiers, 86000, France

Location

Related Publications (2)

• Godet C, Brun AL, Couturaud F, Laurent F, Frat JP, Marchand-Adam S, Gagnadoux F, Blanchard E, Taille C, Philippe B, Hirschi S, Andrejak C, Bourdin A, Chenivesse C, Dominique S, Mangiapan G, Murris-Espin M, Riviere F, Garcia G, Blanc FX, Goupil F, Bergeron A, Flament T, Priou P, Mal H, de Keizer J, Ragot S, Cadranel J; NebuLamB Study Group and GREPI Network. CT Imaging Assessment of Response to Treatment in Allergic Bronchopulmonary Aspergillosis in Adults With Bronchial Asthma. Chest. 2024 Jun;165(6):1307-1318. doi: 10.1016/j.chest.2024.02.026. Epub 2024 Feb 20.

  PMID: 38387646 DERIVED

• 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.

  PMID: 34764182 DERIVED

MeSH Terms

Conditions

Aspergillosis, Allergic Bronchopulmonary

Interventions

liposomal amphotericin B

Condition Hierarchy (Ancestors)

Pulmonary Aspergillosis; Aspergillosis; Mycoses; Bacterial Infections and Mycoses; Infections; Lung Diseases, Fungal; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2014
• First Posted: October 24, 2014
• Study Start: November 19, 2014
• Primary Completion: June 28, 2019
• Study Completion: June 28, 2019
• Last Updated: June 9, 2020

Record last verified: 2020-06

Locations

FR (1)