Sitafloxacin-containing Regimens for Shortening Tuberculosis Treatment

July 7, 2022 updated by: Zhang Ying, First Affiliated Hospital of Zhejiang University

A Randomized Controlled Non-Inferiority Study for Shortening Tuberculosis Treatment With Sitafloxacin-Containing Regimens

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

  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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
620

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age 18 years to 70.
  2. 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.
  3. Phenotypic drug susceptibility testing indicates the patient's isolate is susceptible to rifampin, isoniazid, pyrazinamide, ethambutol, rifapentine, moxifloxacin, and Sitafloxacin.
  4. Patients have written informed consent.

Exclusion Criteria:

  1. Extra-pulmonary or Disseminated TB.
  2. HIV-positive individuals, steroid-dependent and those on steroid treatment.
  3. Autoimmune diseases, severe hepatic or renal dysfunction, psychosis, hematological malignancies, cancer, diabetes individuals.
  4. Known allergy to one or more of the study drugs.
  5. Women who are currently pregnant or breast-feeding.
  6. Patients who received any investigational drug in the past three months.
  7. The patients refused treatment with medications
  8. Mycobacterium tuberculosis/nontuberculous mycobacterium co-infection.
  9. In the investigator's judgment, other medical conditions that are not in the individual's best interest to participate.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: The three-month Rifapentine&Isoniazid&Pyrazinamide&Sitafloxacin-containing regimen
Thirteen weeks of daily treatment with rifapentine, isoniazid, pyrazinamide, and Sitafloxacin.
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.
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)
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
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.
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: Rifampin
Rifampin is a first-line antimicrobial agent against drug-susceptible tuberculosis in WHO guideline, Rifampin 600mg (8-12mg/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)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
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.
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.
Week 17 in the four-month Rifapentine&Isoniazid&Pyrazinamide&Moxifloxacin -containing regimen
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.
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
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
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
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
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
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
Week 26 in the six-month standard Rifampin&Isoniazid&Pyrazinamide&Ethambutol-containing regimen

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
two months
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
Twelve months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
First Affiliated Hospital of Zhejiang University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2022

Primary Completion (ANTICIPATED)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 30, 2025

Study Completion (ANTICIPATED)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 30, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 17, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 7, 2022

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 12, 2022

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 12, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 7, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • yzhang207

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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