Therapeutic efficacy comparison of a six-month treatment by itraconazole and nebulised Ambisome® versus treatment by itraconazole alone in non- or mildly- immunocompromised patients with Chronic Pulmonary Aspergillosis: a prospective, randomized, single blind study, (single aspergilloma excluded).
- Conditions
- MedDRA version: 20.1 Level: LLT Classification code 10022881 Term: Invasive bronchopulmonary aspergillosis System Organ Class: 100000004862Therapeutic area: Body processes [G] - Circulatory and Respiratory Physiological Phenomena [G09]
- Registration Number
- EUCTR2018-000972-14-FR
- Lead Sponsor
- CHU DE POITIERS
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 224
All adult patients affected with CPA de novo” or in relapse (without any history of resistance to itraconazole) combining the following criteria are eligible:
1. Patient with an Aspergillus bronchopulmonary infection over at least 3 months of observation, be it cavitary, fibrotic or nodular and documented by compatible thoracic CT-scan images [8, 16];
2. Associated with one of the following criteria:
-documented anti-Aspergillus IgG and/or precipitin antibodies,
-positive direct examination of Aspergillus or positive culture, from bronchopulmonary samples (expectoration or endoscopic aspiration),
-revealing aspergillar hyphae on histological analysis
3. Men or women age = 18 years;
4. 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;
5. Patient legally free and not subject to any custody, guardianship, tutelage or subordination measures;
6. Participants must be affiliated to France's Health Care Regime (« Sécurité Sociale »);
7. Free and informed consent signed by each participating patient.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 174
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50
1 - Patient affected with single aspergilloma
2 - Patient presenting a contraindication to itraconazole (including contraindicated medications with potential to prolong the QT interval as listed in the itraconazole SmPC)
3- Patient presenting a contraindication to voriconazole or posaconazole
4 – Intolerance to beta2-agonists
5 – Notion of resistance to itraconazole
6 - History of hypersensitivity reaction to liposomal amphotericin B or to itraconazole or to any other constituent
7 - Patient treated by nebulised LAmB during the previous month, or having presented complications related to a previous treatment by nebulised LAmB
8 – Patient received an oral (excepted oral Amphotéricine B), parenteral or intra-cavity antifungal treatment within the last 2 months
9 - Severe renal failure (clearance <30 ml / min).
10 - Hepatic failure with transaminase and alkaline phosphatase values > 5 times normal
11 - Significant abnormality of the blood cell and platelet counts (at the discretion of the investigator)
12 - Concomitant use of one or several of treatments contra-indicated with the experimental or non-experimental treatment
13 - 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.
14 - Invasive pulmonary Aspergillosis, Allergic Bronchopulmonary Aspergillosis
15 - Chronic Pulmonary Aspergillosis with indication for surgical intervention from the start
16 - Patients with Cystic Fibrosis
17 - Immunocompromised patients (HIV Seropositivity, 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
18 - Threatening hemoptysis, with impossibility to defer surgical procedures (but patients contraindicated to surgery may be included after resolution of the hemoptysis)
19 - Tuberculosis or progressive non-tuberculous mycobacteria
20 - Respiratory infection aggravating the underlying CPA (patient may be included after eradication of infection)
21 – Patient refusing to participate
22 – Persons benefiting from enhanced protection, namely minors, persons deprived of their liberty by a judicial or administrative decision, persons staying in a health or social institution, adults under legal protection, and finally patients in emergencies
23 - Patient in exclusion period following participation in another interventional study evaluating antifungals or medicines
24 - Women at age to procreate and not using highly effective contraception (either hormonal / mechanical [oral, injection, subcutaneous, implantable,
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method