This study is a clinical trial conducted to determine whether the sitafloxacin-containing three-month regimens are as effective as the standard six-month regimen and the four-month rifapentine and moxifloxacin regimen (substitution of rifapentine for rifampin and moxifloxacin for ethambutol) for treatment of pulmonary tuberculosis. The standard six-month regimen is two months of isoniazid, rifampin, ethambutol, and pyrazinamide, followed by four months of isoniazid and rifampin. The four-month regimen consists of two months of isoniazid, rifapentine, moxifloxacin, and pyrazinamide, followed by two months of isoniazid rifapentine and moxifloxacin. The new three-month tuberculosis treatment regimens are six weeks of isoniazid, rifapentine, Sitafloxacin, and pyrazinamide, followed by seven weeks of isoniazid, rifapentine, and Sitafloxacin, or 13 weeks of isoniazid, rifapentine, Sitafloxacin, and pyrazinamide. The primary research question is to evaluate the efficacy and safety of the 3 month Sitafloxacin-containing regimen, and to determine if it can shorten the treatment of drug-susceptible pulmonary tuberculosis while achieving non-inferiority in treatment success with the current 6 month and 4 month treatment regimens. Safety, side effects of Sitafloxacin for participants in the clinical trial are also assessed. Rates of cure, treatment success, recurrence, and cure (cure without recurrence) are determined for subgroup analysis in the standard six-month regimen group, the four-month regimen group, and two three-month regimen groups.
1. TB disease-free survival at 13 weeks after study treatment assignment among participants in the three-month regimen group 1 and 2, the four-month regimen group, and the standard six-month regimen. The patients are AFB sputum smear negative or culture negative for M. tuberculosis, two assays are performed (each test is separated by at least seven days), eliminating the M. tuberculosis load from a pulmonary infection. 2. Persons with positive culture results for M. tuberculosis or smear-positive sputum(spoligotyping isolates genetically identified as M. tuberculosis). 3. Data collected pre-study included written informed consent; patients assessed for eligibility; height and weight; clinical symptoms of TB; adjunctive therapy; adverse drug reaction; blood and urine routine; liver and kidney function; acid-fast staining; single M. tuberculosis strain isolated from one patient with TB; GeneXpert MTB/RIF; chest CT scans 4. Clinical symptoms of TB: cough, expectoration, hemoptysis, chest pain, fever, shortness of breath, weak. 5. All patients should review for Xpert MTB/RIF assay in the second week. 6. During treatment, clinical symptoms of TB and body weights takes weekly; blood and urine routine in weeks 1,2,4,8,13; Sputum smears and culture were routinely in weeks 1,2,4,8,13, and months 6 and 12. TB Disease-free Survival at six or twelve months after study treatment assignment as the secondary outcome measures. 7. TB patients were identified through bacteriological confirmation (smear-positive and/or culture-positive). 8. Pulmonary TB patients showed manifestation of tuberculosis by chest CT scans or X-ray. 9. Adverse events of the treatment: neurological diseases, blood system diseases; diseases of the circulatory system; respiratory diseases; digestive diseases; extra-pulmonary TB; diabetes; arthralgia; mental disorders; hemoptysis and pneumothorax; pulmonary embolism; skin rash. 10. Management of a participant with a positive sputum culture for M. tuberculosis at or after week 13: A second sputum sample was collected on the following day for a second culture. If M. tuberculosis is isolated in culture, drug susceptibility testing should be performed on one isolate. Patients will re-evaluate symptoms and chest CT scans; sputum was performed in triplicates and repeated for validation. These patients could restart the standard six-month regimen at any time. 11. Patients follow up one week after the completion of treatment and 6,12,18 months after treatment is over. Patients undergo regular follow-up with sputum smear tests or imaging studies. Patients with positive TB symptom screen or suspected TB patients based on imaging tests are recommended with research staff.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
620
In our Intervention group, sitafloxacin replace the ethambutol, 200mg/d
In our The three-month Rifapentine\&Isoniazid\&Pyrazinamide\&Sitafloxacin\&SMZ/TMP-containing regimen, Six weeks of daily treatment with rifapentine, isoniazid, pyrazinamide, and Sitafloxacin, followed by seven weeks of daily treatment with rifapentine, isoniazid, ,SMZ/TMP and Sitafloxacin, SMZ 80mg/kg/d, TMP16mg/kg/d
Rifampin is a first-line antimicrobial agent against drug-susceptible tuberculosis in WHO guideline, Rifampin 600mg (8-12mg/kg/d)
Pyrazinamide is a first-line antimicrobial agent against drug-susceptible tuberculosis in WHO guideline, 2000mg (20-30mg/kg/d)
In our Intervention group, rifapentine replace rifampin, 600mg/d
Isoniazid is a first-line antimicrobial agent against drug-susceptible tuberculosis in WHO guideline, 300mg (4-6mg/kg/d)
Ethambutol is a first-line antimicrobial agent against drug-susceptible tuberculosis in WHO guideline, 1200mg (15-25mg/kg/d)
Moxifloxacin is a fourth-generation fluoroquinolone with potent activity against M. tuberculosis in vitro and in vivo, 400mg (7.5-10mg/kg/d)
TB Disease-free Survival after the completion of the treatment cycle.
To evaluate the efficacy of a Sitafloxacin-containing regimen to determine whether the substitution of Sitafloxacin for moxifloxacin could shorten the treatment duration from 6 months to 3 months (13 weeks) for drug-susceptible pulmonary tuberculosis. Pathogen detection (including sputum smear and sputum culture) should complete in Week 13 in the three-month regimen group, Week 17 in the four-month regimen group, and Week 26 in the standard six-month regimen group.
Time frame: Week 13 in the three-month Rifapentine&Isoniazid&Pyrazinamide&Sitafloxacin-containing regimen and three-month Rifapentine&Isoniazid&Pyrazinamide&Sitafloxacin&SMZ/TMP-containing regimen
TB Disease-free Survival after the completion of the treatment cycle.
To evaluate the efficacy of a Sitafloxacin-containing regimen to determine whether the substitution of Sitafloxacin for moxifloxacin could shorten the treatment duration from 6 months to 3 months (13 weeks) for drug-susceptible pulmonary tuberculosis. Pathogen detection (including sputum smear and sputum culture) should complete in Week 13 in the three-month regimen group, Week 17 in the four-month regimen group, and Week 26 in the standard six-month regimen group.
Time frame: Week 17 in the four-month Rifapentine&Isoniazid&Pyrazinamide&Moxifloxacin -containing regimen
TB Disease-free Survival after the completion of the treatment cycle.
To evaluate the efficacy of a Sitafloxacin-containing regimen to determine whether the substitution of Sitafloxacin for moxifloxacin could shorten the treatment duration from 6 months to 3 months (13 weeks) for drug-susceptible pulmonary tuberculosis. Pathogen detection (including sputum smear and sputum culture) should complete in Week 13 in the three-month regimen group, Week 17 in the four-month regimen group, and Week 26 in the standard six-month regimen group.
Time frame: Week 26 in the six-month standard Rifampin&Isoniazid&Pyrazinamide&Ethambutol-containing regimen
Percentage Participants With Grade 3 or Higher Adverse Events During Study Drug Treatment in Control Regimen
To determine Grade 3 or higher adverse events in study participants during drug treatment in the standard six-month regimen, the four-month regimen, and the three-month regimen Sitafloxacin-containing and three-month Sitafloxacin\&SMZ/TMP-containing regimen
Time frame: Week 13 in the three-month Rifapentine&Isoniazid&Pyrazinamide&Sitafloxacin-containing regimen and three-month Rifapentine&Isoniazid&Pyrazinamide&Sitafloxacin&SMZ/TMP-containing regimen
Percentage Participants With Grade 3 or Higher Adverse Events During Study Drug Treatment in Control Regimen
To determine Grade 3 or higher adverse events in study participants during drug treatment in the standard six-month regimen, the four-month regimen, and the three-month regimen Sitafloxacin-containing and three-month Sitafloxacin\&SMZ/TMP-containing regimen
Time frame: Week 17 in the four-month Rifapentine&Isoniazid&Pyrazinamide&Moxifloxacin -containing regimen
Percentage Participants With Grade 3 or Higher Adverse Events During Study Drug Treatment in Control Regimen
To determine Grade 3 or higher adverse events in study participants during drug treatment in the standard six-month regimen, the four-month regimen, and the three-month regimen Sitafloxacin-containing and three-month Sitafloxacin\&SMZ/TMP-containing regimen
Time frame: Week 26 in the six-month standard Rifampin&Isoniazid&Pyrazinamide&Ethambutol-containing regimen
The rates of negative sputum conversion
The rates of negative sputum conversion will be determined at the end of 2 months using the sputum smear and culture test.
Time frame: two months
TB disease-free survival at six and twelve months after study treatment assignment.
The rates of TB disease-free survival at six and twelve months
Time frame: Twelve months
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