Chronic Pulmonary Aspergillosis and Ambisome Aerosol with Itraconazole

Launched by POITIERS UNIVERSITY HOSPITAL · Aug 30, 2018

Keywords

ClinConnect Summary

This clinical trial is investigating a new treatment approach for Chronic Pulmonary Aspergillosis (CPA), a lung infection caused by a fungus. The study will compare two treatment methods over six months: one group will receive itraconazole (an antifungal medication) alone, while the other group will also receive nebulized Ambisome (another antifungal) in addition to itraconazole. The goal is to see if combining these treatments leads to better improvements in symptoms and lung health compared to using itraconazole alone.

To participate in the trial, you need to be an adult aged 18 or older with CPA that hasn’t been treated before or is returning after treatment. You should also not have any known resistance to itraconazole. Participants can expect to follow their treatment for six months and then be monitored for an additional two years to see how well the treatment worked. It’s important to know that some individuals, such as those with certain medical conditions or who are currently pregnant or breastfeeding, may not be eligible to participate. If you think you might qualify or want to learn more, discussing this with your healthcare provider could be a great next step.

Gender

ALL

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