Chronic Pulmonary Aspergillosis and Ambisome Aerosol With Itraconazole
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Itraconazole & inhaled placebo Itraconazole 200 mg x 2/day associated with inactive nebulised treatment (isotonic saline) twice a week during 24 weeks. |
Drug: inhaled placebo
inhaled isotonic saline
Other Names:
Drug: Itraconazole
Itraconazole tablet
Other Names:
|
| Experimental: 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 |
Drug: inhaled Ambisome®
inhaled liposomal amphotericin B = inhaled LAmB
Drug: Itraconazole
Itraconazole tablet
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Composite efficacy criterion defined by the association of clinical improvement/stability and radiological improvement evaluated at 6 months [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.
Secondary Outcome Measures
- 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]
Eligibility Criteria
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:
-
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:
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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),
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revealing aspergillar hyphae/filaments on histological samples
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Men or women age ≥ 18 years;
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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;
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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 ");
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Free and informed consent signed by each participating patient.
Exclusion Criteria:
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- Patient affected with single aspergilloma
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- 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)
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- Patient presenting a contraindication to voriconazole or posaconazole (including all contraindicated coadministrated medications as listed in the SmPc)
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- Intolerance to beta2-agonists
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- Notion of relapse with isolation of an Aspergillus resistant to itraconazole
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- History of hypersensitivity reaction to liposomal amphotericin B or to itraconazole or to any other constituent
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- Patient having presented complications related to a previous treatment by nebulised LAmB
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- Patient received an oral (excepted oral Amphotericin B), parenteral or intra-cavity antifungal treatment within the last 2 months
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- Severe renal failure (clearance <30 ml / min).
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- Hepatic failure with transaminase and alkaline phosphatase values > 5 times normal
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- Significant abnormality of the blood cell and platelet counts (at the discretion of the investigator)
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- Concomitant use of one or several of treatments contra-indicated with the experimental or non-experimental treatment
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- 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.
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- Invasive pulmonary Aspergillosis, Allergic Bronchopulmonary Aspergillosis
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- Chronic Pulmonary Aspergillosis with indication for surgical intervention within 6 months from the start
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- Patients with Cystic Fibrosis
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- Immunocompromised patients
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- Threatening hemoptysis, with impossibility to defer surgical procedures (but patients contraindicated to surgery may be included after resolution of the hemoptysis)
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- Tuberculosis or progressive non-tuberculous mycobacteria
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- Respiratory infection aggravating the underlying CPA (patient may be included after eradication of infection)
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- Patient refusing to participate
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- 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.
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- Patient in exclusion period following participation in another interventional study evaluating antifungals or medicines
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- Women at age to procreate and not using highly effective contraception, pregnant or breastfeeding women
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | CHU Poitiers | Poitiers | France | 86000 |
Sponsors and Collaborators
- Poitiers University Hospital
Investigators
- Principal Investigator: Cendrine GODET, MD, Bichat Hospital, AP-HP
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CPAAARI