Chronic Pulmonary Aspergillosis and Ambisome Aerosol with Itraconazole

NCT ID: NCT03656081

Last Updated: 2025-02-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 224 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-19
• Study Completion Date: 2029-12-31

Brief 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.

Conditions

Chronic Pulmonary Aspergillosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Itraconazole & inhaled placebo

Itraconazole 200 mg x 2/day associated with inactive nebulised treatment (isotonic saline) twice a week during 24 weeks.

Group Type: PLACEBO_COMPARATOR

inhaled placebo

Intervention Type: DRUG

inhaled isotonic saline

Itraconazole

Intervention Type: DRUG

Itraconazole tablet

Itraconazole & inhaled Ambisome®

Itraconazole 200 mg x 2/day associated with inhaled liposomal amphotericin B (Ambisome®) at 25 mg twice a week during 24 weeks

Group Type: EXPERIMENTAL

inhaled Ambisome®

Intervention Type: DRUG

inhaled liposomal amphotericin B = inhaled LAmB

Itraconazole

Intervention Type: DRUG

Itraconazole tablet

Interventions

inhaled Ambisome®

inhaled liposomal amphotericin B = inhaled LAmB

Intervention Type: DRUG

inhaled placebo

inhaled isotonic saline

Intervention Type: DRUG

Itraconazole

Itraconazole tablet

Intervention Type: DRUG

Other Intervention Names

placebo (for Ambisome®); Sporanox®

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Poitiers University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Cendrine GODET, MD

Role: PRINCIPAL_INVESTIGATOR

Bichat Hospital, AP-HP

Locations

CHU Poitiers

Poitiers, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Céline DELETAGE

Role: CONTACT

celine.deletage@chu-poitiers.fr

+33 5 49 44 38 54

Facility Contacts

Céline DELETAGE

Role: primary

celine.deletage@chu-poitiers.fr

+33549443854

Other Identifiers

CPAAARI

Identifier Type: -

Identifier Source: org_study_id