Prospective, Randomized, Blinded Phase II Pharmacokinetic/Pharmacodynamic Study of the Efficacy and Tolerability of Levofloxacin in Combination With Optimized Background Regimen for the Treatment of MDR-TB

H-32150

Multi-drug-resistant tuberculosis (MDR-TB) affects nearly 600,000 persons each year around the world. This type of tuberculosis is very difficult to treat, and many patients die from it. Drugs of the fluoroquinolone class are very important for treating MDR-TB, but the best dose of one of the most effective fluoroquinolones, levofloxacin, is not known. This application proposes a study to determine the best dose of levofloxacin to use in treating MDR-TB. 120 patients will receive their usual treatment, plus levofloxacin at one of four doses. The study will be performed in Peru and in South Africa, where MDR-TB is common.

2015-01-01

2022-03-29

2022-03-29

Completed

Early phase I

111

Inclusion Criteria: 1. Patients with smear-positive, culture positive\* pulmonary TB 2. Sputum contains isoniazid\* and rifampin-resistant, Ofloxacin-susceptible MTB, all by MTBDR-sl 3. Previously treated or newly diagnosed with tuberculosis 4. Willingness to have HIV testing performed, if HIV serostatus is not known or if the last documented negative HIV test was more than 3 months prior to enrollment. 5. Age ≥ 18 years. 6. Weight \> 40 Kg 7. Karnofsky score of \> 60 (see section 18.1) 8. Willingness by the patient to attend scheduled follow-up visits and undergo study assessments. 9. Women with child-bearing potential must agree to use birth control if you are having sex with men while participating in this study and for three months afterward. 10. Laboratory parameters (performed within 14 days prior to enrollment): * Estimated Serum creatinine clearance should be \<50, using nomogram78 * Hemoglobin concentration ≥ 9.0 g/dL * Platelet count of ≥ 80,000/mm3 * Absolute neutrophil count (ANC) \> 1000/ mm3 * Negative pregnancy test (for women of childbearing potential) within 14 days of enrollment * HIV viral load and CD4 count if HIV infected (within 3 months) * Serum ALT and total bilirubin \<3 times upper limit of normal 11. Able to provide informed consent Note: \*Subjects may be enrolled on the basis of a presumption that they will be culture positive at either screening or baseline if they are smear-positive, but they will be excluded from the analysis if cultures are subsequently negative. This will not be deemed a protocol violation. Similarly, subjects with rifampin susceptibility on a DNA-based test may be enrolled on the basis of a presumption that they will also be INH-resistant, but they will be excluded from the analysis if the isolate is subsequently shown to be INH-susceptible. This will also not be deemed a protocol violation. Exclusion Criteria: 1. Currently breast-feeding or pregnant. 2. Known allergy or intolerance to or toxicity from fluoroquinolones or other medications utilized in this study. 3. In the judgment of the physician the patient is not expected to survive for 6 months 4. Anticipated surgical intervention for the treatment of pulmonary tuberculosis 5. Participation in another investigational drug trial within the past 30 days 6. Concurrent use of known QT-prolonging drugs: a list of such medications can be found at http://www.azcert.org/medical-pros/drug-lists/printable-drug-list.cfm 7. Poorly controlled diabetes 8. Known g-6-phosphate dehydrogenase deficiency 9. Use of quinolone for 7 days within past 30 days 10. QTc interval greater than 450 msec for men or greater than 470 msec for women

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 111, 'type': 'ACTUAL'}}

2023-05-24