Mycobacterium avium complex pulmonary infections
Conditions
Interventions
Product Name: Clarithromycine
Pharmaceutical Form: Cachet
Product Name: Azithromycine
Pharmaceutical Form: Cachet
Sponsors
CHU Amiens-Picardie
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Clinical criteria ? Respiratory symptoms and the presence of nodular or cavitary lesion on chest x-ray, confirmed on CT-scan. 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 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 424 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Known hypersensitivity to one of the molecules of the study (rifampin, ethambutol, azithromycin, clarithromycin) - Relapse of MAC lung infection - Macrolide resistant stain - Treatment with molecules able to interfere with cytochrome P450 that cannot be replaced by another therapeutic class - HIV 1 and 2 infection - Renal failure with creatinine clearance < 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. - Limited life expectancy (e.g 6 months) - Patient who has already participated in a clinical trial on medicinal product or treatment strategy for NTM
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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.;Secondary Objective: -To compare azithromycin to clarithromycin containing regimen in the MAC lung disease in terms of oTolerance/safety (especially digestive tolerance, hepatitis, drugs interaction) at different time-points oClinical, radiological improvement at 3, 6, 12 months of treatment o3 months- and 12 months- sputum conversion rate o12 months mortality rate -To compare azithromycin and clarithromycin intracellular concentration in plasma and intracellular in circulating mononuclear cells at 1 month and 6 months of treatment, and in hair after 6 months of treatment (nested study) -To correlate azithromycin and clarithromycin intracellular concentration in circulating mononuclear cells with: oMicrobiological success at 6 months oTolerability of treatment. -To evaluate the association between MAC species with 6-month conversion rate.;Primary end point(s): Culture results of respiratory specimens after 6 months of treatment. ;Timepoint(s) of evaluation of this end point: 6 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Safety: digestive toxicity (WHO criteria and Rhodes scale), for hepatitis (cytolysis higher than 3 times normal rate) • Clinical improvement on analogic scales • Radiological improvement on CT scan criteria • 3 and 12 months sputum conversion • 12 months outcome (death) • 1 and 6 months peak serum and mononuclear cells concentration of azithromycin and clarithromycin and their main metabolites • MAC species and 6-month conversion.;Timepoint(s) of evaluation of this end point: 6 months | — |
Countries
France
Contacts
Public ContactLucie DESJARDINS
CHU Amiens-Picardie - DRCI
Outcome results
None listed