Treatment of Mycobacterium Xenopi Pulmonary Infection

Study Overview
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Brief Summary
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The purpose of this study is to determine the 6-months sputum conversion rate with a clarithromycin or moxifloxacin containing regimen in patients with a M. xenopi pulmonary infection.

Detailed Description
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In France, Mycobacterium xenopi is the second non-tuberculous mycobacteria responsible of pulmonary infections. There are few data in the literature regarding its treatment apart from two small randomized trials (42 and 34 patients, respectively) and a French retrospective study (136 patients). So, we decided to conduct a prospective randomized multicenter study to evaluate two treatment regimens for Mycobacterium xenopi pulmonary infection in 6-months sputum conversion. Main objective: To determine the 6-months sputum conversion rate with a clarithromycin or moxifloxacin containing regimen in patients with M.xenopi pulmonary infections according to ATS / IDSA 2007 criteria. Secondary Objectives: To compare the rate of sputum conversion after 3 and 6 months of treatment the clinical and radiological outcome and the 12 months mortality. primary endpoint : Result of culture of respiratory samples 6 months after starting treatment.Culture samples taken 6 months after starting treatment against M. xenopi is either positive (presence of M. xenopi colonies with or without smear positive) or negative with smear and culture negative (see data collection and measurement methods). Study plan: Any patient with at least one positive pulmonary M. xenopi sample may be eligible. If the patient underwent ATS / IDSA 2007 criteria of M. xenopi pulmonary infection (after clinical , radiological and microbiological evaluation), in the absence of exclusion criteria, the patient will be randomized to one of the two treatment arms (rifampicin+ ethambutol + clarithromycin or rifampicin + ethambutol + moxifloxacin). A clinical, radiological, microbiological and pharmacological monitoring will be done for each randomized patient. The recommended treatment duration is 12 months after conversion with a maximum duration of 18 months. Number of patients required: This is a prospective randomized study with 2 parallel groups. The primary endpoint is considered for the whole study population. For an α risk of 5%, an accuracy of 10%, an expected conversion rate of 70% a total of 80 patients is required . For a 15% rate of non evaluable patients (died, lost of follow-up) we need to include 92 patients. Study Duration: Inclusion for 24 months with a minimum follow-up of 6 months (to meet the main objective), and if possible a follow-up of 12 months per patient to meet the overall objectives of the study. Prospects: To establish new treatment recommendations for M.xenopi pulmonary infection, based on microbiological and clinical efficacy criteria and tolerance criteria.

Official Title
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Efficacy of Clarithromycin or Moxifloxacin Containing Regimen in 6 Months Sputum Conversion of Mycobacterium Xenopi

Conditions
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Atypical; Mycobacterium, Pulmonary, Tuberculous

Intervention / Treatment
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* Drug: Clarithromycin
* Drug: Moxifloxacin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient and/or legal representative of the patient has provided a written informed consent before inclusion in the study The patient is aged 18 or older The patient has signs of functional respiratory (cough, sputum, hemoptysis, dyspnea, chest pain and / or general signs (asthenia and / or anorexia and / or weight loss) The patient has a creatinine clearance above 30 ml / min The patient underwent a thoracic scan not older than one month before the first positive bacteriological sample. The patient underwent a bronchoscopy with sampling conducted in the territory corresponding to the radiographic The most plausible alternative diagnostics have been eliminated using the thoracic scan and bronchoscopy The patient has at least two positive cultures for M. xenopi sputum collected on two separate days AND/OR a positive culture for M. xenopi in a bronchoalveolar lavage or bronchial aspiration directed AND / OR transbronchial biopsy or lung biopsy with surgical histology for a mycobacterial infection (granuloma or Ziehl positive) and a culture positive M. xenopi, AND / OR biopsy with histology compatible with mycobacteriosis and one or more positive sputum culture for M . xenopi The patient is willing and able to take the study treatment throughout the duration If this is a woman of childbearing age, the patient is ready to use for the duration of the test contraception method other than estrogen-progestin The patient did not participate in another study evaluating an investigational drug within 30 days prior to enrollment in the study and agrees not to participate in another study for the duration of the study The patient is informed by the doctor and agreed that its data are processed in this study The patient understands / reads French and has no difficulty understanding the objectives of the study The patient has health insurance coverage Exclusion Criteria: Hypersensitivity to any of the molecules (rifampicin, ethambutol, moxifloxacin, clarithromycin) Any patient with a relapse of a lung infection with M. xenopi The patient is treated with molecules that can interfere with cytochrome P450 and can not be replaced by another therapeutic class The patient is treated by prolonging the QT molecules which can not be replaced by another therapeutic class The patient is treated with alkaloid of ergot, cisapride, biperidil, pimozide, mizolastine The patient has heart failure with left ventricular ejection fraction below 30% Discovered on the balance sheet or history, we find that the patient infection with human immunodeficiency virus HIV 1 and 2 a long QT on ECG and / or arrhythmias or clinically significant bradycardia judged by the investigator cytolysis with transaminases increase more than 5 times normal renal failure with creatinine clearance below 30 ml / min The patient has cirrhosis Child Pugh C and / or porphyria There pregnancy or during breastfeeding The patient has an inability to meet the protocol requirements, including active substance abuse, according to the investigator. The patient has a history of tendinopathy with a fluoroquinolone The patient has a congenital galactosemia, malabsorption of glucose and galactose, or lactase deficiency The patient has a NORB (abnormalities of the visual field or color vision tested by an eye examination prior) Any other situation that, in the opinion of the investigator, would imply that participation in the study is not in the interest of the patient There is a risk of difficulty of monitoring, such as imminent transfer to a different region or country

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Clarithromycin<br> | Drug: Clarithromycin<br>* 500 mg twice a day seven days a week<br>* Other names: ZECLAR, NAXY;|
| Experimental: Moxifloxacin<br> | Drug: Moxifloxacin<br>* 400 mg per day seven days a week<br>* Other names: IZILOX;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sputum conversion at 6 months under three antibiotics treatment (Rifampin, ethambutol and a third drug clarithromycin or moxifloxacin) | Results of the smear and culture of three respiratory samples after 6 months of treatment. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sputum conversion at 3, 6, 9 and 12 months of treatment in the two different arms (clarithromycin containing regimen versus moxifloxacin containing regimen | At each endpoint (3, 6, 9 and 12 months), respiratory sample will be analyzed (smear and culture) to answer the second objective (to compare microbiological efficacy of clarithromycin-containing regimen versus moxifloxacin-containing regimen) | 12 months | 
| Clinical and radiological outcome after 3, 6 and 12 months of treatment according to the treatment arm | At each end-point (3, 6 and 12 months) : clinical evaluation with analogic scale (sputum, cough, dyspnea, chest pain, hemoptysis) and weight radiological evaluation: comparison of the size and number of lesions at each endpoint with basal data | 12 months | 
| Mortality after 12 months of treatment in the two compared regimen | Mortality status will be evaluated after 12 months of treatment. In case of deaths under treatment, the date will be collected. Comparative survival analysis will be realized between the two arms of treatment | 12 months | 
| Gastrointestinal toxicity and hematotoxicity after 1- 3- 6- 9- 12- months of treatment | At each end point (1- 3- 6- 9- 12 months), Rhodes score (gastro-intestinal tolerance)and WHO score for hematological, and gastrointestinal toxicity will be collected in the two arms | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mycobacterium Xenopi Pulmonary Infection, Clarithromycin, Moxifloxacin