Preventive therapy for multidrug-resistant tuberculosis: a multicentre clincal trial. - MOXEP

Conditions: Close contacts of an infectious respiratory of a MDR-TB who are diagnosed with tuberculosis infection that is likely to have been acquired from the MDR-TB case will be eligible for inclusion in the study.
MedDRA version: 9.1Level: HLGTClassification code 10028440
MedDRA version: 9.1Level: HLTClassification code 10044756
MedDRA version: 9.1Level: LLTClassification code 10021868

Registration Number: EUCTR2008-006765-82-IT

Lead Sponsor: ISTITUTO NAZIONALE DELLE MALATTIE INFETTIVE LAZZARO SPALLANZANI

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: Not specified

Inclusion Criteria

Close contacts of an infectious respiratory of a MDR-TB who are diagnosed with tuberculosis infection that is likely to have been acquired from the MDR-TB case will be eligible for inclusion in the study Close contacts include [8]: a. Household contacts. Those living in the same household with a MDR-TB case who share a bedroom, kitchen, bathroom or sitting room with the index case. b. Other contacts with a cumulative total exposure to an MDR-TB case exceeding eight hours within a restricted area equivalent to a domestic room. An infectious respiratory MDR TB case is defined as a patients with smear positive respiratory TB for which an M tuberculosis stain isolated from respiratory specimen is identified as resistant to both isoniazid and rifampin Tuberculosis infection likely acquired from an MDR-TB case is defined as positivity (induration equal or greater than 5 mm) [7] of tuberculin skin test (TST) in a contact who has no a prior documented positive TST Among eligible patients other inclusion criteria will be 1.Signed written consent or witnessed oral consent in the case of illiteracy, before undertaking any trial related activity 2.Aged equal or greater than 18 years and less than 66 years 3. Normal chest radiograph obtained after the last contact with the index case 4.Absence of respiratory symptoms or of other sign of symptoms suggestive of active tuberculosis 5.Laboratory tests performed up to 14 days before enrolment 6. Serum aspartate aminotransferase (AST) activity less than two times the Upper Limit of Normal (ULN) 7. Serum total bilirubin level less than two times ULN 8. Haemoglobin level of at least 7.0 g/dL 9. Platelet count of at least 50 x 10^9 cells/L 10.Serum potassium greater than 3.5 mmol/L 11.Negative pregnancy test (women of childbearing potential) 12. Pre-menopausal women must agree to use an effective contraceptive method or to abstain form sexual activity during the period of drug administration.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Exclusion criteria will be: 1.In vitro resistance to any fluoroquinolone and or/to both pyrazinamide and ethambutol of the M tuberculosis isolate from the source patient. 2.Presence of signs or symptoms suggestive of active tuberculosis. 3.Received a course of anti-tuberculosis drugs of at least two months duration. 4.Received a fluoroquinolone or pyrazinamide and ethambutol in the last 28 days. 5. Hypersensitivity to moxifloxacin, to other quinolones or any other ingredients; hypersensitivity to ethambutol and pirazinamide. 6.Received any investigational drug in the past three months. 7. Any condition that may prove fatal during the first two months of the study period. 8. Pre-existing non-tuberculosis disease likely to prejudice the response to, or assessment of, treatment e.g. insulin-dependent diabetes, liver or kidney disease, blood disorders, peripheral neuritis, chronic diarrhoeal disease. 9. Evidence of optic neuritis (visual field and color differentiation tests must be included in the first examination) or previous diagnosis of eye disease. 10. Porphyria, hyperuricemia if accompanied by gout or arthritis. 11.Pregnant or breast feeding. 12.Contraindications to any medication in the study regimens. 13.Suffering from a condition likely to lead to uncooperative behaviour /and or to increase the risk of adverse events e.g. psychiatric illness, alcoholism central nervous system or peripheral nervous system diseases. 14. Documented QT prolongation, congenital or acquired; clinically significant Bradycardia - Heart failure with reduced ejection fraction, left ventricular clinically significant history of symptomatic arrhythmias. 15. Contemporary use of other drugs that can cause a prolongation of QTc (eg, amiodarone, sotalol, disopyramide, quinidine, procainamide, terfenadine). 16. History of tendon disorders associated to the use of fluoroquinolones. 17. End stage liver failure (class Child-Pugh C). 18.Uncorrected hypokalaemia. 19. Celiac disease or lactose intolerance. 20. Body weight lower than 40 kg.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Specific objective of the present study are to evaluate safety and tolerability of moxifoxacin given in combination with pyrazinamide or with ethambutol for four months to close contacts of MDR TB cases, by measuring the incidence of adverse effects and the rate of discontinuation due to adverse effects.;Secondary Objective: Further objectives are to provide a preliminary estimate of treatment efficacy by comparing two-years incidence of tuberculosis among treated individuals with that of the control group and to verify whether preventive therapy may be associated with the emergence of further drug resistance.;Primary end point(s): 1.Discontinuation rate: Proportion of individuals that permanently discontinue treatment due to adverse events 2.Safety : Proportion of patients with grade three or four adverse events according to the WHO grade ; grading of adverse events will be based on clinical evaluation and laboratory parameters.

Secondary Outcome Measures