Clinical trial NCT01298336: Treatment of Mycobacterium Xenopi Pulmonary Infection
Official title: Efficacy of Clarithromycin or Moxifloxacin Containing Regimen in 6 Months Sputum Conversion of Mycobacterium Xenopi
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Atypical; Mycobacterium, Pulmonary, Tuberculous
Keywords: Mycobacterium Xenopi Pulmonary Infection
Clarithromycin
Moxifloxacin
Lead sponsor: Centre Hospitalier Universitaire, Amiens
Sponsor class: OTHER
First posted: 2011-02-17
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility 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

Primary outcomes:
measure: Sputum conversion at 6 months under three antibiotics treatment (Rifampin, ethambutol and a third drug clarithromycin or moxifloxacin)
timeFrame: 6 months
Secondary outcomes:
measure: Sputum conversion at 3, 6, 9 and 12 months of treatment in the two different arms (clarithromycin containing regimen versus moxifloxacin containing regimen
timeFrame: 12 months
measure: Clinical and radiological outcome after 3, 6 and 12 months of treatment according to the treatment arm
timeFrame: 12 months
measure: Mortality after 12 months of treatment in the two compared regimen
timeFrame: 12 months
measure: Gastrointestinal toxicity and hematotoxicity after 1- 3- 6- 9- 12- months of treatment
timeFrame: 12 months
Other outcomes:
Locations:
city: Abbeville
country: France
facility: CH Abbeville
city: Amiens
country: France
facility: CHU Amiens
city: Angers
country: France
facility: CHU Angers
city: Argenteuil
country: France
facility: CH Argenteuil
city: Besançon
country: France
facility: CHU Besançon
city: Bobigny
country: France
facility: Assistance Publique Hôpitaux de Paris CHU Avicenne
city: Brest
country: France
facility: CHU Brest La Cavale
city: Béthune
country: France
facility: CH Béthune
city: Caen
country: France
facility: CHU Caen
city: Cannes
country: France
facility: CH Cannes
city: Clermont Ferrand
country: France
facility: CHU Clermont Ferrand Hôpital Gabriel Mont pied
city: Compiègne
country: France
facility: CH Compiègne
city: Corbeil-Essonnes
country: France
facility: CH Sud Francilien
city: Creteil
country: France
facility: Centre Intercommunal de Créteil
city: Dijon
country: France
facility: CHU Dijon
city: Gonesse
country: France
facility: CH Gonesse
city: Grenoble
country: France
facility: CHU Grenoble
city: Le Kremlin-Bicêtre
country: France
facility: Assistance Publique Hôpitaux de Paris Hôpital Bicetre
city: Le Mans
country: France
facility: CH Le MANS
city: Les Mureaux
country: France
facility: CH Intercommunal Meulan
city: Lille
country: France
facility: CHU Lille Hôpital Calmette
city: Limoges
country: France
facility: CHU Limoges Hôpital de Cluzeau
city: Lyon
country: France
facility: CHU Lyon Hôpital La Croix Rousse
city: Marseille
country: France
facility: Hopital Saint-Joseph
city: Marseille
country: France
facility: Assistance Publique Hôpitaux de Marseille
city: Montpellier
country: France
facility: CHU Montpellier Hôpital Arnaud de Villeneuve
city: Nantes
country: France
facility: CHU Nantes
city: Nice
country: France
facility: CHU Nice
city: Orléans
country: France
facility: Chr Orleans
city: Paris
country: France
facility: Assistance Publique Hôpitaux de Paris Hôpital Saint Louis
city: Paris
country: France
facility: Assistance Publique Hôpitaux de Paris Hôpital Saint Antoine
city: Paris
country: France
facility: Centre National de Reference Des Mycobactéries
city: Paris
country: France
facility: Assistance Publique Hôpitaux de Paris Hôpital BICHAT
city: Paris
country: France
facility: Assistance Publique Hôpitaux de Paris, hôpital TENON
city: Pessac
country: France
facility: CHU Bordeaux Hôpital Haut Leveque
city: Poitiers
country: France
facility: CHU Poitiers
city: Pontoise
country: France
facility: Hopital René DUBOS
city: Reims
country: France
facility: CHU Reims
city: Rennes
country: France
facility: CHU de Rennes Hôpital Ponchaillou
city: Roubaix
country: France
facility: CH de Roubaix
city: Rouen
country: France
facility: CHU Rouen
city: Saint Etienne
country: France
facility: CHU de Saint Etienne
city: Saint Quentin
country: France
facility: CH de Saint Quentin
city: Saint-Nazaire
country: France
facility: CH Saint-Nazaire
city: Strasbourg
country: France
facility: CHU de Strasbourg
city: Suresnes
country: France
facility: Hôpital FOCH
city: Toulouse
country: France
facility: CHU Toulouse
city: Tourcoing
country: France
facility: CH de Tourcoing
city: Tours
country: France
facility: CHU Tours Hôpital BRETONNEAU
city: Troyes
country: France
facility: CH Troyes
city: Valenciennes
country: France
facility: CH de Valenciennes
city: Vandœuvre-lès-Nancy
country: France
facility: CHU Nancy
Study officials:
affiliation: Centre Hospitalier Universitaire, Amiens
name: Claire ANDREJAK, Dr
role: STUDY_DIRECTOR
affiliation: CHU Amiens
name: Claire ANDREJAK, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU Amiens
name: Vincent JOUNIEAUX, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: APHP Pitie Salpetriere Hospital, National Center Of Mycobacteria
name: Nicolas VEZIRIS, MD-PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Tenon Hospital APHP Paris
name: Jacques CADRANEL, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Tenon hospital APHP Paris
name: Francois-Xavier LESCURE, MD
role: PRINCIPAL_INVESTIGATOR
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