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

NCT03236987 | Recruiting Phase 3

• 1 other identifier: PI2017_843_0010
• Study Type: interventional
• Target: 424
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Lung Infection; MAC Lung Disease

Keywords

Clarithromycin; Azithromycin; Efficacy; Safety

Outcome Measures

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.

  6 months

Secondary Outcomes (10)

• Clinical improvement

  3 months

• Clinical improvement

  6 months

• Clinical improvement

  12 months

• Radiological improvement

  3 months

• Radiological improvement

  6 months

Study Arms (2)

Clarithromycin 1000 MG

ACTIVE COMPARATOR

The patient will received a combination of 3 antibiotics : * Rifampicin (10mg/kg once daily) * Ethambutol (15 to 20 mg/kg once daily) * Clarithromycin (500 mg twice daily)

Drug: Clarithromycin 1000 MG; Drug: Rifampicin; Drug: Ethambutol

Azithromycin 250 MG

EXPERIMENTAL

The patient will received a combination of 3 antibiotics : * Rifampicin (10mg/kg once daily) * Ethambutol (15 to 20 mg/kg once daily) * Azithromycin (250 mg once daily)

Drug: Azithromycin 250 mg; Drug: Rifampicin; Drug: Ethambutol

Interventions

Clarithromycin 1000 MG DRUG

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

Also known as: ZECLAR

Clarithromycin 1000 MG

Azithromycin 250 mg DRUG

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

Also known as: ZITHROMAX

Azithromycin 250 MG

Rifampicin DRUG

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.

Also known as: RIFADINE

Azithromycin 250 MG; Clarithromycin 1000 MG

Ethambutol DRUG

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.

Also known as: DEXAMBUTOL

Azithromycin 250 MG; Clarithromycin 1000 MG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Known hypersensitivity to one of the study molecules (rifampicin, ethambutol, azithromycin, clarithromycin)
• Relapse of an MAC infection,
• 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.

Sponsors & Collaborators

• Centre Hospitalier Universitaire, Amiens: lead

Study Sites (3)

CHU Amiens Picardie

Amiens, Picardie, 80054, France

NOT YET RECRUITING

CHU Angers

Angers, 49933, France

RECRUITING

Saint Joseph Hospital

Marseille, 13000, France

RECRUITING

MeSH Terms

Interventions

Clarithromycin; Azithromycin; Rifampin; Ethambutol

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Ethylenediamines; Diamines; Polyamines; Amines

Study Officials

• Didier RENAUT

  CHU Amiens-Picardie

  STUDY DIRECTOR

Central Study Contacts

Claire ANDREJAK, PhD

CONTACT

+33322087893; andrejak.claire@chu-amiens.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2017
• First Posted: August 2, 2017
• Study Start: February 5, 2018
• Primary Completion (Estimated): February 5, 2028
• Study Completion (Estimated): February 5, 2029
• Last Updated: November 19, 2025

Record last verified: 2025-11

Locations

FR (3)