Sitafloxacin-containing Regimens for Shortening Tuberculosis Treatment
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ClinicalTrials.gov Identifier: NCT05454345 |
Recruitment Status :
Not yet recruiting
First Posted : July 12, 2022
Last Update Posted : July 12, 2022
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Sponsor:
First Affiliated Hospital of Zhejiang University
Information provided by (Responsible Party):
Zhang Ying, First Affiliated Hospital of Zhejiang University
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Brief Summary:
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.
Condition or disease | Intervention/treatment | Phase |
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Tuberculosis, Pulmonary | Drug: Sitafloxacin Drug: SMZ/TMP Drug: Rifampin Drug: Pyrazinamide Drug: Rifapentine Drug: Isoniazid Drug: Ethambutol Drug: Moxifloxacin | Phase 3 |
- 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.
- Persons with positive culture results for M. tuberculosis or smear-positive sputum(spoligotyping isolates genetically identified as M. tuberculosis).
- 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
- Clinical symptoms of TB: cough, expectoration, hemoptysis, chest pain, fever, shortness of breath, weak.
- All patients should review for Xpert MTB/RIF assay in the second week.
- 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.
- TB patients were identified through bacteriological confirmation (smear-positive and/or culture-positive).
- Pulmonary TB patients showed manifestation of tuberculosis by chest CT scans or X-ray.
- 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.
- 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.
- 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 (Clinical Trial) |
Estimated Enrollment : | 620 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Randomized Controlled Non-Inferiority Study for Shortening Tuberculosis Treatment With Sitafloxacin-Containing Regimens |
Estimated Study Start Date : | October 1, 2022 |
Estimated Primary Completion Date : | June 30, 2025 |
Estimated Study Completion Date : | June 30, 2026 |
Resource links provided by the National Library of Medicine
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MedlinePlus related topics:
Tuberculosis
Arm | Intervention/treatment |
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Experimental: The three-month Rifapentine&Isoniazid&Pyrazinamide&Sitafloxacin-containing regimen
Thirteen weeks of daily treatment with rifapentine, isoniazid, pyrazinamide, and Sitafloxacin.
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Drug: Sitafloxacin
In our Intervention group, sitafloxacin replace the ethambutol, 200mg/d Drug: Pyrazinamide Pyrazinamide is a first-line antimicrobial agent against drug-susceptible tuberculosis in WHO guideline, 2000mg (20-30mg/kg/d) Drug: Rifapentine In our Intervention group, rifapentine replace rifampin, 600mg/d Drug: Isoniazid Isoniazid is a first-line antimicrobial agent against drug-susceptible tuberculosis in WHO guideline, 300mg (4-6mg/kg/d) |
Experimental: 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.
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Drug: Sitafloxacin
In our Intervention group, sitafloxacin replace the ethambutol, 200mg/d Drug: SMZ/TMP 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 Drug: Pyrazinamide Pyrazinamide is a first-line antimicrobial agent against drug-susceptible tuberculosis in WHO guideline, 2000mg (20-30mg/kg/d) Drug: Rifapentine In our Intervention group, rifapentine replace rifampin, 600mg/d Drug: Isoniazid Isoniazid is a first-line antimicrobial agent against drug-susceptible tuberculosis in WHO guideline, 300mg (4-6mg/kg/d) |
Active Comparator: The six-month standard Rifampin&Isoniazid&Pyrazinamide&Ethambutol-containing regimen
Eight weeks of daily treatment with rifampin, isoniazid, pyrazinamide, and ethambutol, followed by Eighteen weeks of daily treatment with rifampin and isoniazid.
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Drug: Rifampin
Rifampin is a first-line antimicrobial agent against drug-susceptible tuberculosis in WHO guideline, Rifampin 600mg (8-12mg/kg/d) Drug: Pyrazinamide Pyrazinamide is a first-line antimicrobial agent against drug-susceptible tuberculosis in WHO guideline, 2000mg (20-30mg/kg/d) Drug: Isoniazid Isoniazid is a first-line antimicrobial agent against drug-susceptible tuberculosis in WHO guideline, 300mg (4-6mg/kg/d) Drug: Ethambutol Ethambutol is a first-line antimicrobial agent against drug-susceptible tuberculosis in WHO guideline, 1200mg (15-25mg/kg/d) |
Active Comparator: The four-month Rifapentine&Isoniazid&Pyrazinamide&Moxifloxacin -containing regimen
Eight weeks of daily treatment with rifapentine, isoniazid, pyrazinamide, and moxifloxacin, followed by Nine weeks of daily treatment with rifapentine, isoniazid, and moxifloxacin.
|
Drug: Rifapentine
In our Intervention group, rifapentine replace rifampin, 600mg/d Drug: Isoniazid Isoniazid is a first-line antimicrobial agent against drug-susceptible tuberculosis in WHO guideline, 300mg (4-6mg/kg/d) Drug: Ethambutol Ethambutol is a first-line antimicrobial agent against drug-susceptible tuberculosis in WHO guideline, 1200mg (15-25mg/kg/d) Drug: Moxifloxacin Moxifloxacin is a fourth-generation fluoroquinolone with potent activity against M. tuberculosis in vitro and in vivo, 400mg (7.5-10mg/kg/d) |
Primary Outcome Measures :
- TB Disease-free Survival after the completion of the treatment cycle. [ 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 ]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.
- TB Disease-free Survival after the completion of the treatment cycle. [ Time Frame: Week 17 in the four-month Rifapentine&Isoniazid&Pyrazinamide&Moxifloxacin -containing regimen ]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.
- TB Disease-free Survival after the completion of the treatment cycle. [ Time Frame: Week 26 in the six-month standard Rifampin&Isoniazid&Pyrazinamide&Ethambutol-containing regimen ]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.
- Percentage Participants With Grade 3 or Higher Adverse Events During Study Drug Treatment in Control 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 ]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
- Percentage Participants With Grade 3 or Higher Adverse Events During Study Drug Treatment in Control Regimen [ Time Frame: Week 17 in the four-month Rifapentine&Isoniazid&Pyrazinamide&Moxifloxacin -containing 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
- Percentage Participants With Grade 3 or Higher Adverse Events During Study Drug Treatment in Control Regimen [ Time Frame: Week 26 in the six-month standard Rifampin&Isoniazid&Pyrazinamide&Ethambutol-containing 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
Secondary Outcome Measures :
- The rates of negative sputum conversion [ Time Frame: two months ]The rates of negative sputum conversion will be determined at the end of 2 months using the sputum smear and culture test.
- TB disease-free survival at six and twelve months after study treatment assignment. [ Time Frame: Twelve months ]The rates of TB disease-free survival at six and twelve months
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Ages Eligible for Study: | 18 Years to 70 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Age 18 years to 70.
- At least one sputum specimen is positive for acid-fast bacilli or positive results of sputum culture on smear microscopy(species identification as M. tuberculosis) or at least one sputum specimen positive for M. tuberculosis by Xpert MTB/RIF testing.
- Phenotypic drug susceptibility testing indicates the patient's isolate is susceptible to rifampin, isoniazid, pyrazinamide, ethambutol, rifapentine, moxifloxacin, and Sitafloxacin.
- Patients have written informed consent.
Exclusion Criteria:
- Extra-pulmonary or Disseminated TB.
- HIV-positive individuals, steroid-dependent and those on steroid treatment.
- Autoimmune diseases, severe hepatic or renal dysfunction, psychosis, hematological malignancies, cancer, diabetes individuals.
- Known allergy to one or more of the study drugs.
- Women who are currently pregnant or breast-feeding.
- Patients who received any investigational drug in the past three months.
- The patients refused treatment with medications
- Mycobacterium tuberculosis/nontuberculous mycobacterium co-infection.
- In the investigator's judgment, other medical conditions that are not in the individual's best interest to participate.
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Additional Information:
Publications:
Publications:
Responsible Party: | Zhang Ying, Prof, MD, First Affiliated Hospital of Zhejiang University |
ClinicalTrials.gov Identifier: | NCT05454345 |
Other Study ID Numbers: |
yzhang207 |
First Posted: | July 12, 2022 Key Record Dates |
Last Update Posted: | July 12, 2022 |
Last Verified: | July 2022 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
Tuberculosis Tuberculosis, Pulmonary Mycobacterium Infections Actinomycetales Infections Gram-Positive Bacterial Infections Bacterial Infections Bacterial Infections and Mycoses Infections Respiratory Tract Infections Lung Diseases Respiratory Tract Diseases Moxifloxacin Rifampin Isoniazid Pyrazinamide |
Ethambutol Rifapentine Sitafloxacin Anti-Bacterial Agents Anti-Infective Agents Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Antibiotics, Antitubercular Antitubercular Agents Leprostatic Agents Nucleic Acid Synthesis Inhibitors Cytochrome P-450 CYP2B6 Inducers |