RecruitingPhase 3NCT03236987

CLArithromycin Versus AZIthromycin in the Treatment of Mycobacterium Avium Complex (MAC) Lung Infections


Sponsor

Centre Hospitalier Universitaire, Amiens

Enrollment

424 participants

Start Date

Feb 5, 2018

Study Type

INTERVENTIONAL

Conditions

Summary

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

Min Age: 18 Years

Inclusion Criteria4

  • 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 Criteria11

  • 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.

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Interventions

DRUGClarithromycin 1000 MG

The patient will be received for at least 12 months, a daily antibiotic treatment who is a combination of Clarithromycin, Ethambutol and Rifampicin.

DRUGAzithromycin 250 mg

The patient will be received for at least 12 months, a daily antibiotic treatment who is a combination of Azithromycin, Ethambutol and Rifampicin.

DRUGRifampicin

The 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.

DRUGEthambutol

The 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.


Locations(3)

CHU Amiens Picardie

Amiens, Picardie, France

CHU Angers

Angers, France

Saint Joseph Hospital

Marseille, France

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NCT03236987


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