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Chronic Pulmonary Aspergillosis and Ambisome Aerosol With Itraconazole

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ClinicalTrials.gov Identifier: NCT03656081
Recruitment Status : Recruiting
First Posted : September 4, 2018
Last Update Posted : June 21, 2019
Sponsor:
Information provided by (Responsible Party):
Poitiers University Hospital

Tracking Information
First Submitted Date  ICMJE July 19, 2018
First Posted Date  ICMJE September 4, 2018
Last Update Posted Date June 21, 2019
Actual Study Start Date  ICMJE December 19, 2018
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 30, 2018)
Composite efficacy criterion defined by the association of clinical improvement/stability and radiological improvement evaluated at 6 months [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 30, 2018)
  • major events during follow-up period [ Time Frame: month 6 to month 30 ]
  • relapse [ Time Frame: month 6 to month 30 ]
  • mycological response [ Time Frame: after 3 months and 6 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Chronic Pulmonary Aspergillosis and Ambisome Aerosol With Itraconazole
Official Title  ICMJE 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)
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Condition  ICMJE Chronic Pulmonary Aspergillosis
Intervention  ICMJE
  • Drug: inhaled Ambisome®
    inhaled liposomal amphotericin B = inhaled LAmB
  • Drug: inhaled placebo
    inhaled isotonic saline
    Other Name: placebo (for Ambisome®)
  • Drug: Itraconazole
    Itraconazole tablet
    Other Name: Sporanox®
Study Arms  ICMJE
  • Placebo Comparator: Itraconazole & inhaled placebo
    Itraconazole 200 mg x 2/day associated with inactive nebulised treatment (isotonic saline) twice a week during 24 weeks.
    Interventions:
    • Drug: inhaled placebo
    • Drug: Itraconazole
  • 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
    Interventions:
    • Drug: inhaled Ambisome®
    • Drug: Itraconazole
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 30, 2018)
224
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2023
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 or 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Marie Bonnin +33 5 49 44 33 17 marie.bonnin@chu-poitiers.fr
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03656081
Other Study ID Numbers  ICMJE CPAAARI
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Poitiers University Hospital
Study Sponsor  ICMJE Poitiers University Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Cendrine GODET, MD Bichat Hospital, AP-HP
PRS Account Poitiers University Hospital
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP