Treatment of Mycobacterium Xenopi Pulmonary Infection

Atypical; Mycobacterium, Pulmonary, Tuberculous Clinical Trial

— CAMOMY  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01298336
• Other study ID #: PHRCN10-DR-ANDREJAK-MELLE
• Status: Completed
• Phase: Phase 3
• Start date: March 2, 2011
• Est. completion date: March 2019

Study information

• Verified date: July 2020
• Source: Centre Hospitalier Universitaire, Amiens
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 92
• Est. completion date: March 2019
• Est. primary completion date: March 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Atypical; Mycobacterium, Pulmonary, Tuberculous
• Mycobacterium Infections
• Mycobacterium Infections, Nontuberculous

Intervention

Drug:
• Clarithromycin
500 mg twice a day seven days a week
• Moxifloxacin
400 mg per day seven days a week

Locations

Country	Name	City	State
France	CH Abbeville	Abbeville
France	CHU Amiens	Amiens
France	CHU Angers	Angers
France	CH Argenteuil	Argenteuil
France	CHU Besançon	Besançon
France	CH Béthune	Béthune
France	Assistance Publique Hôpitaux de Paris CHU Avicenne	Bobigny
France	CHU Brest La Cavale	Brest
France	CHU Caen	Caen
France	CH Cannes	Cannes
France	CHU Clermont Ferrand Hôpital Gabriel Mont pied	Clermont Ferrand
France	CH Compiègne	Compiègne
France	CH Sud Francilien	Corbeil-Essonnes
France	Centre Intercommunal de Créteil	Creteil
France	CHU Dijon	Dijon
France	CH Gonesse	Gonesse
France	CHU Grenoble	Grenoble
France	Assistance Publique Hôpitaux de Paris Hôpital Bicetre	Le Kremlin-Bicêtre
France	CH Le MANS	Le Mans
France	CH Intercommunal Meulan	Les Mureaux
France	CHU Lille Hôpital Calmette	Lille
France	CHU Limoges Hôpital de Cluzeau	Limoges
France	CHU Lyon Hôpital La Croix Rousse	Lyon
France	Assistance Publique Hôpitaux de Marseille	Marseille
France	Hopital Saint-Joseph	Marseille
France	CHU Montpellier Hôpital Arnaud de Villeneuve	Montpellier
France	CHU Nantes	Nantes
France	CHU Nice	Nice
France	Chr Orleans	Orléans
France	Assistance Publique Hôpitaux de Paris Hôpital BICHAT	Paris
France	Assistance Publique Hôpitaux de Paris Hôpital Saint Antoine	Paris
France	Assistance Publique Hôpitaux de Paris Hôpital Saint Louis	Paris
France	Assistance Publique Hôpitaux de Paris, hôpital TENON	Paris
France	Centre National de Reference Des Mycobactéries	Paris
France	CHU Bordeaux Hôpital Haut Leveque	Pessac
France	CHU Poitiers	Poitiers
France	Hopital René DUBOS	Pontoise
France	CHU Reims	Reims
France	CHU de Rennes Hôpital Ponchaillou	Rennes
France	CH de Roubaix	Roubaix
France	CHU Rouen	Rouen
France	CHU de Saint Etienne	Saint Etienne
France	CH de Saint Quentin	Saint Quentin
France	CH Saint-Nazaire	Saint-Nazaire
France	CHU de Strasbourg	Strasbourg
France	Hôpital FOCH	Suresnes
France	CHU Toulouse	Toulouse
France	CH de Tourcoing	Tourcoing
France	CHU Tours Hôpital BRETONNEAU	Tours
France	CH Troyes	Troyes
France	CH de Valenciennes	Valenciennes
France	CHU Nancy	Vandœuvre-lès-Nancy

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire, Amiens

Country where clinical trial is conducted

France, 

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* Note: There are 48 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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