Treatment of Mycobacterium Xenopi Pulmonary Infection
Treatment of Mycobacterium Xenopi Pulmonary Infection
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.
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.
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