CLArithromycin Versus AZIthromycin in the Treatment of Mycobacterium Avium Complex (MAC) Lung Infections
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorCentre Hospitalier Universitaire, Amiens
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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,
Trial design
Design model
Parallel
Treatments tested in this trial
Clarithromycin 1000 MG
DrugThe patient will be received for at least 12 months, a daily antibiotic treatment who is a combination of Clarithromycin, Ethambutol and Rifampicin.
Azithromycin 250 mg
DrugThe patient will be received for at least 12 months, a daily antibiotic treatment who is a combination of Azithromycin, Ethambutol and Rifampicin.
Rifampicin
DrugThe patient will be received for at least 12 months, a dailty antibiotic treatment who is a combination of Azithromycin or Clarithromycin (according to the randomisation), Ethambutol and Rifampicin.
Ethambutol
DrugThe patient will be received for at least 12 months, a dailty antibiotic treatment who is a combination of Azithromycin or Clarithromycin (according to the randomisation), Ethambutol and Rifampicin.
Treatment groups
424 Participants
are divided into 2 treatment groupsGroup A: Clarithromycin 1000 MGActive comparator 3 interventions
Group B: Azithromycin 250 MGExperimental treatment 3 interventions
Trial outcomes
Primary outcomes
1
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.
Time frame
6 monthsSecondary outcomes
1
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).
Time frame
3 months2
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).
Time frame
6 months3
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).
Time frame
12 months4
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)
Time frame
3 monthsSponsors and contacts
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Source ClinicalTrials.gov