CPAAARI-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).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Poitiers

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Phenomena and Processes [G] - Circulatory and Respiratory Physiological Phenomena [G09]

Trial duration

22 Oct 2024 → ongoing

Decision date (initial)

2024-10-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

VIVISOL · ELIVIE · CHU de Poitiers · SOS OXYGEN · ORHE PHARMA · MSD MERCK · PFIZER · JASSEN CILAG · DGOS france

External identifiers

EU CT number

2024-517004-11-00

EudraCT number

2018-000972-14

ClinicalTrials.gov

NCT03656081

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

Compare the therapeutic (clinical and radiological) efficacy of a six-month treatment by itraconazole and nebulised Ambisome® versus treatment by itraconazole alone, in non - or mildly - immunocompromised patients affected by Chronic Pulmonary Aspergillosis (single aspergilloma excluded).

Secondary objectives 8

1. To compare both strategies regarding clinical and/or radiological evolution after 3 and 6 months,
2. To compare both strategies regarding major events during follow-up period (M6-M30
3. To compare both strategies regarding relapse between M6 and M30
4. To compare both strategies regarding mycological response after 3 (M3) and 6 months (M6)
5. To compare both strategies regarding number of medical consultations or hospitalizations for respiratory symptoms
6. To compare both strategies regarding clinical and biological tolerance
7. To compare both strategies regarding improvement in quality of life evaluated by the VQ-11 Questionnaire
8. To estimate concordance for CPA diagnosis and CPA evolution under treatment between clinical, radiological, mycological and serological parameters

Conditions and MedDRA coding

Chronic pulmonary aspergillosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

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: 1-positive detection of anti-Aspergillus IgG and/or precipitating anti-Aspergillus antibodies, according to the positivity threshold of the laboratory performing the technique/2-positive direct examination of Aspergillus or positive culture, from bronchopulmonary samples (expectoration or endoscopic aspiration)/3-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 24

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 Amphotéricine 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 QTc interval > 450 msec in men and 470 msec in women or treated by medication known to prolong QT interval, or prolongation of the QTc 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 (HIV Seropositivity (except if the disease is controlled and with no contraindications between azole and antiretroviral treatments), AIDS, progressive neoplastic disease, systemic disease in active phase, immunosuppressor treatment, allograft or autograft of bone marrow, haematologic disease (acute or chronic leukaemia, multiple myeloma, Hodgkin's disease …), organ transplants, neutropenia (ANC < 500 / mm3) during the 3 months preceding the inclusion, systemic corticotherapy > 7,5 mg / day prednisolone (or equivalent) > 3 weeks
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 (either hormonal / mechanical [oral, injection, subcutaneous, implantable, intrauterine device] or surgical [tubal ligation, hysterectomy, total ovariectomy]: at least as concerns the initial 12 months of the study, pregnant or breastfeeding women

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Therapeutic efficacy at 6 months is a composite criterion defined by the association of clinical improvement/stability and radiological improvement.

Secondary endpoints 8

1. -Clinical evolution after 3 or 6 months: patient will be classified in one of 3 classes: improvement or stability or clinical deterioration./-Radiological evolution after 3 or 6 months: patient will be classified in one of 3 classes: improvement or stability or deterioration
2. -Major events during the 24-months follow-up period after stopping study treatment (i.e.; between visit M6 (at 6 months) and visit M30 (at 30 months).
3. Relapse during the 24-months follow-up period after stopping study treatment (between visits M6 and M30).
4. Mycological response after 3 and 6 months of study treatment.
5. Number of medical consultations or hospitalizations for respiratory symptoms during the 6-month study treatment and the 24-month follow-up period
6. Clinical and biological tolerance
7. Improvement in quality of life evaluated by the VQ-11 Questionnaire
8. Concordance evaluation assessment between parameters for CPA diagnosis and evolution (see ancillary project annex 3 of this protocol)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 3

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Poitiers

Sponsor organisation

Centre Hospitalier Universitaire De Poitiers

Address

2 Rue De La Miletrie

City

Poitiers

Postcode

86000

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Poitiers

Contact name

Dr Cendrine GODET

Public contact point

Organisation

Centre Hospitalier Universitaire De Poitiers

Contact name

Dr Cendrine GODET

Locations

1 EU/EEA country · 41 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 19 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications