CLAZI : CLArithromycin versus AZIthromycin in the treatment of Mycobacterium avium complex pulmonary infections: A randomized prospective controlled study
- Conditions
- Is to demonstrate a non inferior efficacy of azithromycin and so the possibility for clinician to choose between two drugs for Mycobacterium avium complex treatment.
- Registration Number
- 2024-518578-15-00
- Lead Sponsor
- Centre Hospitalier Universitaire Amiens Picardie
- Brief Summary
To demonstrate the non-inferiority in term of 6-month sputum conversion rate of azithromycin- to clarithromycin-containing regimen in the Mycobacterium avium complex (MAC) lung disease treatment.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised, recruiting
- Sex
- Not specified
- Target Recruitment
- 424
In order to be included, each eligible patient, 18 years old or orlder, must present ATS/IDSA 2007 criteria for nontuberculous mycobacterial pulmonary infection (3). These criteria are as follows: - Clinical criteria o Respiratory symptoms and the presence of nodular or cavitary lesion on chest highresolution computed tomography. Lesions may also present in the form of diffuse micronodular syndrome.
AND Microbiological criteria : At least two positive cultures for MAC on two sputum specimens obtained on two different days
AND/OR : Positive culture for MAC on bronchoalveolar lavage or bronchoscopic aspiration
AND/OR : Transbronchial biopsy or surgical lung biopsy presenting histology in favour of mycobacterial infection (granuloma or positive Ziehl-Neelsen stain) and positive culture for MAC OR biopsy showing histology compatible with mycobacterial infection and one or more sputum cultures positive for MAC
AND : Exclusion of other diagnoses on CT scan, bronchoscopy and bacteriological specimens. In the presence of common bacteria, persistence of clinical symptoms and radiological signs after well-conducted antibiotic therapy suggests the diagnosis of MAC infection. The presence of criteria of Aspergillus fumigatus infection associated with the presence of microbiological criteria of MAC infection will lead to the diagnosis of MAC and Aspergillus fumigatus co-infection
Known hypersensitivity to one of the molecules of the study (rifampin, ethambutol, azithromycin, clarithromycin)
Limited life expectancy (e.g 6 months)
Patients with hematologic malignancies and allogeneic haematopoietic stem cells
Women of childbearing age and not using an effective method of contraception (Pearl Index <1%)
The patient is treated with molecules prolonging the QT interval that cannot be replaced by another therapeutic class
The patient presents a heart failure with left ventricular ejection fraction less than 30%
Patient already participating in a clinical trial of a treatment or a therapeutic strategy for non-mycobacterial Tubercular
Relapse of MAC lung infection
Macrolide resistant strain, based on genotyping susceptibility testing (must be done before inclusion)
Treatment with molecules able to interfere with cytochrome P450 that cannot be replaced by another therapeutic class
HIV 1 and 2 human immunodeficiency virus infection
Renal failure with creatinine clearance less than 30 mL/min
Pregnancy and breastfeeding
Contraindications to one of the antibiotic
Inability to comply with the requirements of the protocol, especially substance abuse, according to the investigator
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method The primary endpoint is the 6-month negative sputum conversion rate. The primary endpoint is the 6-month negative sputum conversion rate.
- Secondary Outcome Measures
Name Time Method For safety: digestive toxicity (WHO criteria and Rhodes scale (28, 29)), for hepatitis (cytolysis higher than 3 times normal rate) For safety: digestive toxicity (WHO criteria and Rhodes scale (28, 29)), for hepatitis (cytolysis higher than 3 times normal rate)
Clinical improvement on analogic scales Clinical improvement on analogic scales
Radiological improvement on CT scan criteria (dimensions of the lesions compared to the baseline CT, classified as complete resolution of the lesions, partial resolution of the lesions: reduction of at least 50% of the lesions, stabilization: size of the lesion between 50% and 130% compared to baseline, deterioration of lesions: appearance of new lesions or greater than 30% Radiological improvement on CT scan criteria (dimensions of the lesions compared to the baseline CT, classified as complete resolution of the lesions, partial resolution of the lesions: reduction of at least 50% of the lesions, stabilization: size of the lesion between 50% and 130% compared to baseline, deterioration of lesions: appearance of new lesions or greater than 30%
3 and 12 months sputum conversion (Culture results of respiratory specimens taken 3 and 12 months after starting treatment) 3 and 12 months sputum conversion (Culture results of respiratory specimens taken 3 and 12 months after starting treatment)
12 months outcome (death) 12 months outcome (death)
1 month and 6 months peak serum and mononuclear cells concentration of azithromycin and clarithromycin and their main metabolites (D-azithromycin and 14-OH clarithromycin respectively) determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) 1 month and 6 months peak serum and mononuclear cells concentration of azithromycin and clarithromycin and their main metabolites (D-azithromycin and 14-OH clarithromycin respectively) determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS)
MAC species and 6-month conversion MAC species and 6-month conversion
Trial Locations
- Locations (50)
Assistance Publique Hopitaux De Paris
🇫🇷Paris, France
Centre Hospitalier Et Universitaire De Limoges
🇫🇷Limoges Cedex 1, France
Centre Hospitalier Universitaire De Poitiers
🇫🇷Poitiers, France
Centre Hospitalier Universitaire De Saint Etienne
🇫🇷St Etienne Cedex 2, France
Centre Hospitalier Le Mans
🇫🇷Le Mans Cedex 9, France
Hospital Foch
🇫🇷Suresnes, France
Centre Hospitalier Universitaire De Lille
🇫🇷Lille, France
Centre Hospitalier Regional De Marseille
🇫🇷Marseille, France
Centre Hospitalier Regional Et Universitaire De Brest
🇫🇷Brest, France
Centre Hospitalier De Cannes Simone Veil
🇫🇷Cannes Cedex, France
Scroll for more (40 remaining)Assistance Publique Hopitaux De Paris🇫🇷Paris, FranceBruno CRESTANISite contact0140256910bruno.crestani@aphp.frNicolas VEZIRISSite contact0149283041nicolas.veziris@sorbonne-universite.frDiane BOUVRYSite contact0148955004diane.bouvry@aphp.frJacques CADRANELSite contact0156016147jacques.cadranel@tnn.aphp.frPierre Régis BURGELSite contact0158412367pierre-regis.burgel@aphp.frAbdellatif TAZISite contact0142494166abdellatif.tazi@aphp.frAlexandra SERRISSite contact0142192719alexandra.serris@aphp.fr