chronic pulmonary aspergillosis and ambisome aerosol with itraconazole

Conditions: Chronic Pulmonary Aspergillosis

Summary: this study compares the therapeutic (clinical and radiological) efficacy of a six-month treatment by itraconazole and nebulised ambisome® (liposomal amphotericin b = lamb) versus treatment by itraconazole alone, in non - or mildly - immunocompromised patients affected by chronic pulmonary aspergillosis (single aspergilloma excluded). • control arm: itraconazole 200 mg x 2/day associated with inactive nebulised treatment twice a week during 24 weeks. • experimental arm: itraconazole 200 mg x 2/day associated with nebulised lamb, at 25 mg twice a week during 24 weeks. follow up duration for the patients will be 24 months (12 months minimum) after discontinuation of the treatment being studied.


Eligibility criteria:
inclusion criteria: all adult patients affected with chronic pulmonary aspergillosis (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, be it cavitary, fibrotic, necrotizing (sia/semi invasive aspergillosis) or nodular and documented by compatible thoracic ct-scan images ; 2. associated with one of the following criteria: * positive detection of anti-aspergillus igg and/or precipitating anti-aspergillus antibodies, according to the positivity threshold of the laboratory performing the technique, * positive direct examination of aspergillus or positive culture, from bronchopulmonary samples (expectoration or endoscopic aspiration), * revealing aspergillar hyphae/filaments on histological samples 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. exclusion criteria: 1. - patient affected with single aspergilloma 2. - 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) 3. - patient presenting a contraindication to voriconazole and posaconazole (including all contraindicated coadministrated medications as listed in the smpc) 4. - intolerance to beta2-agonists 5. - notion of relapse with isolation of an aspergillus resistant to itraconazole 6. - history of hypersensitivity reaction to liposomal amphotericin b or to itraconazole or to any other constituent 7. - patient having presented complications related to a previous treatment by nebulised lamb 8. - patient received an oral (excepted oral amphotericin 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 corrected qt interval \> 450 msec in men and 470 msec in women or treated by medication known to prolong qt interval, or prolongation of the corrected qt 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 within 6 months from the start 16. - patients with cystic fibrosis 17. - immunocompromised patients 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. - 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. 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, pregnant or breastfeeding women