Lung Infection Clinical Trial
— CLAZIOfficial title:
CLArithromycin Versus AZIthromycin in the Treatment of Mycobacterium Avium Complex (MAC) Lung Infections
MAC lung infections are a growing public health problem. The ATS / IDSA 2007 guidelines for the treatment of these non-tuberculous mycobacterial infections recommend the use of a macrolide or azalide (clarithromycin or azithromycin), rifampicin or rifabutin and ethambutol. For MAC disseminated infections, several studies have compared combinations containing clarithromycin or azithromycin and found no significant difference in efficacy. No randomized controlled trials have been performed for pulmonary infections to compare clarithromycin and azithromycin in terms of efficacy. Clarithromycin is often used as a first-line treatment in France, but its tolerance is often poor, particularly in terms of risk of hepatitis, metallic taste in the mouth, nausea or vomiting, and it interacts with many drugs via cytochrome p450 . In particular, it increases the toxicity of rifabutin, in particular in terms of uveitis. Azithromycin has fewer side effects especially less digestive toxicity and drug interactions than clarithromycin. The hypothesis is therefore that the efficacy of azithromycin would be non-inferior in comparison with that of clarithromycin.
Status | Recruiting |
Enrollment | 424 |
Est. completion date | February 1, 2025 |
Est. primary completion date | February 1, 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - patients 18 years of age or older - having a positive Mycobacterium avium complex sample showing the ATS / IDSA infection criteria and requiring treatment - ATS / IDSA infection criteria combine clinico-radiological criteria, associated with microbiological criteria - the exclusion of any other diagnosis on the thoracic CT, fibroscopy and bacteriological samples Exclusion Criteria: - Known hypersensitivity to one of the study molecules (rifampicin, ethambutol, azithromycin, clarithromycin) - Relapse of an MAC infection, - Strain resistant to macrolides, based on genotyping susceptibility testing (genotyping susceptibility testing must be done before inclusion) - Treatment that interacts with cytochrome p450 that can not be replaced by another therapeutic, - HIV serology 1 and 2, - Renal insufficiency with creatinine clearance less than 30 ml / min, - Pregnancy and breast feeding, - Contra-indication to one of the antibiotics, - Impossibility to follow the protocol due in particular to drug addiction according to the investigator, - Limited life expectancy, less than 6 months, - Patient already participating in a clinical trial on a medical treatment or a therapeutic strategy for non-tuberculous mycobacteria. |
Country | Name | City | State |
---|---|---|---|
France | CHU Amiens Picardie | Amiens | Picardie |
France | Saint Joseph Hospital | Marseille |
Lead Sponsor | Collaborator |
---|---|
Centre Hospitalier Universitaire, Amiens |
France,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Culture results of respiratory specimens taken 6 months after starting treatment. | Three spontaneous sputum specimens will be obtained at baseline and 6 months. If it's not possible to obtain good quality specimens, the clinician may perform three hypertonic aerosol-induced sputum specimens on 3 consecutive days. In the absence of sputum (spontaneous or induced), bronchoscopic aspiration and two post-bronchoscopy sputum specimens will be performed.
Microscopic examination will be performed after auramine or Ziehl-Neelsen stain. Specimens will be cultured at 37°C after decontamination on Lowenstein-Jensen solid medium and Coletsos medium. Results will be expressed quantitatively as the number of colonies per tube according to a logarithmic scale. Culture on liquid medium will also be performed. The analysis will be based on the Mycobacteria National Reference Centre microscopy, culture and antibiotic susceptibility test results. |
6 months | |
Secondary | Clinical improvement | Several criteria will be determined at baseline and at 3 months and then compared to assess clinical improvement :
Presence or absence of cough, sputum, dyspnoea, chest pain and wheezing using a 5-point analogue scale (0=no symptom, 4=permanent symptoms) ; WHO performance status scored from 0 to 4 ; Global score from 0 to 24, taking into account the score of the 5 respiratory symptoms and the WHO performance status ; Presence of blood-stained sputum (haemoptysis greater than 50 mL or requiring specialized medical intervention) Weight in kg (patient weighed in underwear on the same scales, variations taken into account when greater than 5% of the baseline weight). |
3 months | |
Secondary | Clinical improvement | Several criteria will be determined at baseline and at 6 months and then compared to assess clinical improvement :
Presence or absence of cough, sputum, dyspnoea, chest pain and wheezing using a 5-point analogue scale (0=no symptom, 4=permanent symptoms) ; WHO performance status scored from 0 to 4 ; Global score from 0 to 24, taking into account the score of the 5 respiratory symptoms and the WHO performance status ; Presence of blood-stained sputum (haemoptysis greater than 50 mL or requiring specialized medical intervention) Weight in kg (patient weighed in underwear on the same scales, variations taken into account when greater than 5% of the baseline weight). |
6 months | |
Secondary | Clinical improvement | Several criteria will be determined at baseline and at 12 months and then compared to assess clinical improvement :
Presence or absence of cough, sputum, dyspnoea, chest pain and wheezing using a 5-point analogue scale (0=no symptom, 4=permanent symptoms) ; WHO performance status scored from 0 to 4 ; Global score from 0 to 24, taking into account the score of the 5 respiratory symptoms and the WHO performance status ; Presence of blood-stained sputum (haemoptysis greater than 50 mL or requiring specialized medical intervention) Weight in kg (patient weighed in underwear on the same scales, variations taken into account when greater than 5% of the baseline weight). |
12 months | |
Secondary | Radiological improvement | Chest x-ray will be realised at baseline and at 3 months and described according to :
type of lesion: opacity/solitary pulmonary nodule, excavated opacity/ fibrocavitary disease, interstitial syndrome (multiple nodule, dense airspace disease) precise site (upper lobe, right middle or lower lobe, left lower or upper lobe) |
3 months | |
Secondary | Radiological improvement | Chest x-ray and chest high-resolution CT will be realised at baseline and at 6 months.
Chest x-ray will be described according to: type of lesion: opacity/solitary pulmonary nodule, excavated opacity/ fibrocavitary disease, interstitial syndrome (multiple nodule, dense airspace disease) precise site (upper lobe, right middle or lower lobe, left lower or upper lobe) Chest CT will be described according to: type of lesion: nodules, micronodules, bronchiectasis, mass, interstitial syndrome (and its type) precise site of the segment(s) involved number of lesions dimensions of the various lesions (long and short axes) and volume, whenever possible. |
6 months | |
Secondary | Radiological improvement | Chest x-ray and chest high-resolution CT will be realised at baseline and at 12 months.
Chest x-ray will be described according to: type of lesion: opacity/solitary pulmonary nodule, excavated opacity/ fibrocavitary disease, interstitial syndrome (multiple nodule, dense airspace disease) precise site (upper lobe, right middle or lower lobe, left lower or upper lobe) Chest CT will be described according to: type of lesion: nodules, micronodules, bronchiectasis, mass, interstitial syndrome (and its type) precise site of the segment(s) involved number of lesions dimensions of the various lesions (long and short axes) and volume, whenever possible. |
12 months | |
Secondary | Sputum conversion (culture results of respiratory specimens) | Microbiological specimens, preferably 3 sputum specimens, will be obtained and processed at 3 months after treatment according to the same modalities as at baseline. | 3 months | |
Secondary | Sputum conversion (culture results of respiratory specimens) | Microbiological specimens, preferably 3 sputum specimens, will be obtained and processed at 12 months after treatment according to the same modalities as at baseline. | 12 months | |
Secondary | Survival analysis | The 12-month mortality will be determined by the survival at that date. The date of any death occurring during treatment will be recorded and the interval between the start of treatment and death will be calculated. The cause of death will be investigated and reported. | 12 months | |
Secondary | Safety as assessed by adverse events according to the Rhodes scale, and hematological, gastrointestinal and renal toxicities according to the WHO toxicity scale | All adverse events will be notified according to the recommendations. Particular attention will be paid to gastrointestinal adverse effects (the incidence of nausea and vomiting will be recorded). These adverse events will be assessed at each visit according to the Rhodes scale.
Haematological, gastrointestinal and renal toxicities will be scored according to the WHO toxicity scale. |
12 months |
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