Chronic Pulmonary Aspergillosis and Ambisome Aerosol with Itraconazole

NCT03656081 | Recruiting Phase 3

• 1 other identifier: CPAAARI
• Study Type: interventional
• Target: 224
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Composite efficacy criterion defined by the association of clinical improvement/stability and radiological improvement evaluated at 6 months

  • Clinical improvement or stability is evaluated using the Respiratory Symptom Score based on 6 items (cough, expectoration, dyspnea, hemoptysis, chest pain, and nocturnal awakening ) quoted with a 10 cm visual analogical scale). Stability is defined by a score variation between -25 and +25%, while improvement is defined by a decrease in score greater than 25%. • Radiological improvement is based on the analysis of CT-scan parameters (a committee consisting on two chest radiologists wil perform centrally and parallel analyses of each CT-scan blinded to the study treatment allocation to reach a final decision by consensus) The radiological improvement (binary variable) is defined by a consensual score based on the evolution of the various radiological parameters (cavity, fungus ball, alveolar condensation, nodules) according to validated thresholds.

  6 months

Secondary Outcomes (3)

• major events during follow-up period

  month 6 to month 30

• relapse

  month 6 to month 30

• mycological response

  after 3 months and 6 months

Study Arms (2)

Itraconazole & inhaled placebo

PLACEBO COMPARATOR

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

Drug: inhaled placebo; Drug: Itraconazole

Itraconazole & inhaled Ambisome®

EXPERIMENTAL

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

Drug: inhaled Ambisome®; Drug: Itraconazole

Interventions

inhaled Ambisome® DRUG

inhaled liposomal amphotericin B = inhaled LAmB

Itraconazole & inhaled Ambisome®

inhaled placebo DRUG

inhaled isotonic saline

Also known as: placebo (for Ambisome®)

Itraconazole & inhaled placebo

Itraconazole DRUG

Itraconazole tablet

Also known as: Sporanox®

Itraconazole & inhaled Ambisome®; Itraconazole & inhaled placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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 ;
• 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
• Men or women age ≥ 18 years;
• 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;
• Patient legally free and not subject to any custody, guardianship, tutelage or subordination measures;
• Participants must be affiliated to France's Health Care Regime (" Sécurité Sociale ");
• Free and informed consent signed by each participating patient.

You may not qualify if:

• \- Patient affected with single aspergilloma
• \- 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)
• \- Patient presenting a contraindication to voriconazole and posaconazole (including all contraindicated coadministrated medications as listed in the SmPc)
• \- Intolerance to beta2-agonists
• \- Notion of relapse with isolation of an Aspergillus resistant to itraconazole
• \- History of hypersensitivity reaction to liposomal amphotericin B or to itraconazole or to any other constituent
• \- Patient having presented complications related to a previous treatment by nebulised LAmB
• \- Patient received an oral (excepted oral Amphotericin B), parenteral or intra-cavity antifungal treatment within the last 2 months
• \- Severe renal failure (clearance \<30 ml / min).
• \- Hepatic failure with transaminase and alkaline phosphatase values \> 5 times normal
• \- Significant abnormality of the blood cell and platelet counts (at the discretion of the investigator)
• \- Concomitant use of one or several of treatments contra-indicated with the experimental or non-experimental treatment
• \- 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.
• \- Invasive pulmonary Aspergillosis, Allergic Bronchopulmonary Aspergillosis
• \- Chronic Pulmonary Aspergillosis with indication for surgical intervention within 6 months from the start

Sponsors & Collaborators

• Poitiers University Hospital: lead

Study Sites (1)

CHU Poitiers

Poitiers, 86000, France

RECRUITING

MeSH Terms

Interventions

Itraconazole

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines

Study Officials

• Cendrine GODET, MD

  Bichat Hospital, AP-HP

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Céline DELETAGE

CONTACT

+33 5 49 44 38 54; celine.deletage@chu-poitiers.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2018
• First Posted: September 4, 2018
• Study Start: December 19, 2018
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2029
• Last Updated: February 20, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)