Comparing two treatments for Chronic Pulmonary Aspergillosis

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)

This study is testing if a combination of two treatments can help people with Chronic Pulmonary Aspergillosis feel better compared to using just one of the treatments alone.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 224 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Poitiers University Hospital (other)
• Locations: 1 site (Poitiers)
• Trial ID: NCT03656081 on ClinicalTrials.gov

What this trial studies

This study evaluates the effectiveness of a six-month treatment regimen combining itraconazole with nebulized Ambisome® (liposomal amphotericin B) against itraconazole alone in patients with Chronic Pulmonary Aspergillosis. Participants will be randomly assigned to receive either the combination treatment or itraconazole with a placebo nebulizer. The study aims to assess both clinical and radiological outcomes over a follow-up period of 24 months after treatment cessation. Eligible patients include those with documented Aspergillus infections and no history of itraconazole resistance.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with a confirmed diagnosis of Chronic Pulmonary Aspergillosis.

Not a fit: Patients with a history of resistance to itraconazole or those with single aspergillomas may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve outcomes for patients suffering from Chronic Pulmonary Aspergillosis.

How similar studies have performed: Other studies have explored treatments for Chronic Pulmonary Aspergillosis, but the combination of nebulized Ambisome with itraconazole is a novel approach.

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

Where this trial is running

Poitiers

• CHU Poitiers — Poitiers, France (RECRUITING)

Study contacts

• Principal investigator: Cendrine GODET, MD — Bichat Hospital, AP-HP
• Study coordinator: Céline DELETAGE

Conditions: Chronic Pulmonary Aspergillosis