AMPHOTERICINE B, LIPOSOME for Chronic pulmonary aspergillosis

Inclusion criteria

• {"criterion_text":"- Patient with an Aspergillus bronchopulmonary infection, be it cavitary, fibrotic, necrotizing (SIA/Semi Invasive Aspergillosis) or nodular and documented by compatible thoracic CT-scan images"}
• {"criterion_text":"- Associated with one of the following criteria: 1-positive detection of anti-Aspergillus IgG and/or precipitating anti-Aspergillus antibodies, according to the positivity threshold of the laboratory performing the technique/2-positive direct examination of Aspergillus or positive culture, from bronchopulmonary samples (expectoration or endoscopic aspiration)/3-revealing aspergillar hyphae/filaments on histological samples"}
• {"criterion_text":"- Men or women age ≥ 18 years"}
• {"criterion_text":"- For the women of childbearing age: women having a negative serum pregnancy test, having a contraception highly effective and accepting to pursue it during at least the first 12 months of the study"}
• {"criterion_text":"- Patient legally free and not subject to any custody, guardianship, tutelage or subordination measures"}
• {"criterion_text":"- Participants must be affiliated to France's Health Care Regime (« Sécurité Sociale »);"}
• {"criterion_text":"- Free and informed consent signed by each participating patient."}

Exclusion criteria

• {"criterion_text":"- Patient affected with single aspergilloma"}
• {"criterion_text":"- Hepatic failure with transaminase and alkaline phosphatase values > 5 times normal"}
• {"criterion_text":"- Significant abnormality of the blood cell and platelet counts (at the discretion of the investigator)"}
• {"criterion_text":"- Concomitant use of one or several of treatments contra-indicated with the experimental or non-experimental treatment"}
• {"criterion_text":"- Ventricular dysfunction such as congestive cardiac failure or history of congestive cardiac failure or patients with risk(s) factors of cardiac arrhythmia or symptomatic arrhythmia with a prolongation of the QTc interval > 450 msec in men and 470 msec in women or treated by medication known to prolong QT interval, or prolongation of the QTc interval > 450 msec in men and 470 msec in women"}
• {"criterion_text":"- Invasive pulmonary Aspergillosis, Allergic Bronchopulmonary Aspergillosis"}
• {"criterion_text":"- Chronic Pulmonary Aspergillosis with indication for surgical intervention within 6 months from the start"}
• {"criterion_text":"- Patients with Cystic Fibrosis"}
• {"criterion_text":"- Immunocompromised patients (HIV Seropositivity (except if the disease is controlled and with no contraindications between azole and antiretroviral treatments), AIDS, progressive neoplastic disease, systemic disease in active phase, immunosuppressor treatment, allograft or autograft of bone marrow, haematologic disease (acute or chronic leukaemia, multiple myeloma, Hodgkin's disease …), organ transplants, neutropenia (ANC < 500 / mm3) during the 3 months preceding the inclusion, systemic corticotherapy > 7,5 mg / day prednisolone (or equivalent) > 3 weeks"}
• {"criterion_text":"- Threatening hemoptysis, with impossibility to defer surgical procedures (but patients contraindicated to surgery may be included after resolution of the hemoptysis)"}
• {"criterion_text":"- Tuberculosis or progressive non-tuberculous mycobacteria"}
• {"criterion_text":"- Patient presenting a contraindication to itraconazole (including all contraindicated co-administrated medications as listed in the itraconazole SmPc, including notably medications with potential to prolong theQT interval)"}
• {"criterion_text":"- Respiratory infection aggravating the underlying CPA (patient may be included after eradication of infection)"}
• {"criterion_text":"- Patient refusing to participate"}
• {"criterion_text":"- Protected majors in the meaning of the law, non affiliated persons or with no social security scheme, persons deprived of liberty by a judicial or administrative decision, persons staying in a health or social institution, adults under legal protection, and finally patients in emergencies."}
• {"criterion_text":"- Patient in exclusion period following participation in another interventional study evaluating antifungals or medicines"}
• {"criterion_text":"- Women at age to procreate and not using highly effective contraception (either hormonal / mechanical [oral, injection, subcutaneous, implantable, intrauterine device] or surgical [tubal ligation, hysterectomy, total ovariectomy]: at least as concerns the initial 12 months of the study, pregnant or breastfeeding women"}
• {"criterion_text":"- Patient presenting a contraindication to voriconazole and posaconazole (including all contraindicated coadministrated medications as listed in the SmPc)."}
• {"criterion_text":"- Intolerance to beta2-agonists"}
• {"criterion_text":"- Notion of relapse with isolation of an Aspergillus resistant to itraconazole"}
• {"criterion_text":"- History of hypersensitivity reaction to liposomal amphotericin B or to itraconazole or to any other constituent"}
• {"criterion_text":"- Patient having presented complications related to a previous treatment by nebulised LAmB"}
• {"criterion_text":"- Patient received an oral (excepted oral Amphotéricine B), parenteral or intra-cavity antifungal treatment within the last 2 months"}
• {"criterion_text":"- Severe renal failure (clearance <30 ml / min"}

Primary endpoints

• {"endpoint_text":"- Therapeutic efficacy at 6 months is a composite criterion defined by the association of clinical improvement/stability and radiological improvement.","definition_or_measurement_approach":"Composite criterion defined by the association of clinical improvement/stability and radiological improvement evaluated at 6 months (visit M6)."}

Secondary endpoints

• {"endpoint_text":"- -Clinical evolution after 3 or 6 months: patient will be classified in one of 3 classes: improvement or stability or clinical deterioration./-Radiological evolution after 3 or 6 months: patient will be classified in one of 3 classes: improvement or stability or deterioration","definition_or_measurement_approach":"Clinical and radiological evolution after 3 and 6 months: classification into one of three classes (improvement, stability, deterioration)."}
• {"endpoint_text":"- -Major events during the 24-months follow-up period after stopping study treatment (i.e.; between visit M6 (at 6 months) and visit M30 (at 30 months).","definition_or_measurement_approach":"Capture of major events occurring between M6 and M30 (24-month follow-up after treatment)."}
• {"endpoint_text":"- Relapse during the 24-months follow-up period after stopping study treatment (between visits M6 and M30).","definition_or_measurement_approach":"Relapse assessment during 24-month follow-up after treatment cessation (between M6 and M30)."}
• {"endpoint_text":"- Mycological response after 3 and 6 months of study treatment.","definition_or_measurement_approach":"Mycological response assessed at months 3 and 6."}
• {"endpoint_text":"- Number of medical consultations or hospitalizations for respiratory symptoms during the 6-month study treatment and the 24-month follow-up period","definition_or_measurement_approach":"Count of medical consultations or hospitalisations for respiratory symptoms during treatment (6 months) and follow-up (24 months)."}
• {"endpoint_text":"- Clinical and biological tolerance","definition_or_measurement_approach":"Assessment of clinical and biological (laboratory) tolerability during study treatment and follow-up."}
• {"endpoint_text":"- Improvement in quality of life evaluated by the VQ-11 Questionnaire","definition_or_measurement_approach":"Quality of life measured by the VQ-11 questionnaire at scheduled visits."}
• {"endpoint_text":"- Concordance evaluation assessment between parameters for CPA diagnosis and evolution (see ancillary project annex 3 of this protocol)","definition_or_measurement_approach":"Concordance assessment between clinical, radiological, mycological and serological parameters (see ancillary project annex)."}

France

Earliest CTIS Part Ii Submission Date

23-09-2024

Latest Decision Or Authorization Date

20-01-2026

Processing Time Days

484

Number Of Sites

42

Number Of Participants

224

Primary sponsor

Full Name

Centre Hospitalier Universitaire De Poitiers

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"VIVISOL","duties_or_roles":"Monetary support","organisation_type":""}
• {"country":"","full_name":"ELIVIE","duties_or_roles":"Monetary support","organisation_type":""}
• {"country":"","full_name":"CHU de Poitiers","duties_or_roles":"Monetary support","organisation_type":""}
• {"country":"","full_name":"SOS OXYGEN","duties_or_roles":"Monetary support","organisation_type":""}
• {"country":"","full_name":"ORHE PHARMA","duties_or_roles":"Monetary support","organisation_type":""}
• {"country":"","full_name":"MSD MERCK","duties_or_roles":"Monetary support","organisation_type":""}
• {"country":"","full_name":"PFIZER","duties_or_roles":"Monetary support","organisation_type":""}
• {"country":"","full_name":"JASSEN CILAG","duties_or_roles":"Monetary support","organisation_type":""}
• {"country":"","full_name":"DGOS france","duties_or_roles":"Monetary support","organisation_type":""}