Sitafloxacin-containing Regimens for Shortening Tuberculosis Treatment

NCT05454345 | Not Yet Recruiting Phase 3

• 1 other identifier: yzhang207
• Study Type: interventional
• Target: 620
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Tuberculosis, Pulmonary

Outcome Measures

Primary Outcomes (6)

• 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.

  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.

  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.

  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

  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

  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

  Week 26 in the six-month standard Rifampin&Isoniazid&Pyrazinamide&Ethambutol-containing regimen

Secondary Outcomes (2)

• The rates of negative sputum conversion

  two months

• TB disease-free survival at six and twelve months after study treatment assignment.

  Twelve months

Study Arms (4)

The three-month Rifapentine&Isoniazid&Pyrazinamide&Sitafloxacin-containing regimen

EXPERIMENTAL

Thirteen weeks of daily treatment with rifapentine, isoniazid, pyrazinamide, and Sitafloxacin.

Drug: Sitafloxacin; Drug: Pyrazinamide; Drug: Rifapentine; Drug: Isoniazid

The three-month Rifapentine&Isoniazid&Pyrazinamide&Sitafloxacin&SMZ/TMP-containing regimen

EXPERIMENTAL

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; Drug: SMZ/TMP; Drug: Pyrazinamide; Drug: Rifapentine; Drug: Isoniazid

The six-month standard Rifampin&Isoniazid&Pyrazinamide&Ethambutol-containing regimen

ACTIVE COMPARATOR

Eight weeks of daily treatment with rifampin, isoniazid, pyrazinamide, and ethambutol, followed by Eighteen weeks of daily treatment with rifampin and isoniazid.

Drug: Rifampin; Drug: Pyrazinamide; Drug: Isoniazid; Drug: Ethambutol

The four-month Rifapentine&Isoniazid&Pyrazinamide&Moxifloxacin -containing regimen

ACTIVE COMPARATOR

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; Drug: Isoniazid; Drug: Ethambutol; Drug: Moxifloxacin

Interventions

Sitafloxacin DRUG

In our Intervention group, sitafloxacin replace the ethambutol, 200mg/d

The three-month Rifapentine&Isoniazid&Pyrazinamide&Sitafloxacin&SMZ/TMP-containing regimen; The three-month Rifapentine&Isoniazid&Pyrazinamide&Sitafloxacin-containing regimen

SMZ/TMP DRUG

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

The three-month Rifapentine&Isoniazid&Pyrazinamide&Sitafloxacin&SMZ/TMP-containing regimen

Rifampin DRUG

Rifampin is a first-line antimicrobial agent against drug-susceptible tuberculosis in WHO guideline, Rifampin 600mg (8-12mg/kg/d)

The six-month standard Rifampin&Isoniazid&Pyrazinamide&Ethambutol-containing regimen

Pyrazinamide DRUG

Pyrazinamide is a first-line antimicrobial agent against drug-susceptible tuberculosis in WHO guideline, 2000mg (20-30mg/kg/d)

The six-month standard Rifampin&Isoniazid&Pyrazinamide&Ethambutol-containing regimen; The three-month Rifapentine&Isoniazid&Pyrazinamide&Sitafloxacin&SMZ/TMP-containing regimen; The three-month Rifapentine&Isoniazid&Pyrazinamide&Sitafloxacin-containing regimen

Rifapentine DRUG

In our Intervention group, rifapentine replace rifampin, 600mg/d

The four-month Rifapentine&Isoniazid&Pyrazinamide&Moxifloxacin -containing regimen; The three-month Rifapentine&Isoniazid&Pyrazinamide&Sitafloxacin&SMZ/TMP-containing regimen; The three-month Rifapentine&Isoniazid&Pyrazinamide&Sitafloxacin-containing regimen

Isoniazid DRUG

Isoniazid is a first-line antimicrobial agent against drug-susceptible tuberculosis in WHO guideline, 300mg (4-6mg/kg/d)

The four-month Rifapentine&Isoniazid&Pyrazinamide&Moxifloxacin -containing regimen; The six-month standard Rifampin&Isoniazid&Pyrazinamide&Ethambutol-containing regimen; The three-month Rifapentine&Isoniazid&Pyrazinamide&Sitafloxacin&SMZ/TMP-containing regimen; The three-month Rifapentine&Isoniazid&Pyrazinamide&Sitafloxacin-containing regimen

Ethambutol DRUG

Ethambutol is a first-line antimicrobial agent against drug-susceptible tuberculosis in WHO guideline, 1200mg (15-25mg/kg/d)

The four-month Rifapentine&Isoniazid&Pyrazinamide&Moxifloxacin -containing regimen; The six-month standard Rifampin&Isoniazid&Pyrazinamide&Ethambutol-containing regimen

Moxifloxacin DRUG

Moxifloxacin is a fourth-generation fluoroquinolone with potent activity against M. tuberculosis in vitro and in vivo, 400mg (7.5-10mg/kg/d)

The four-month Rifapentine&Isoniazid&Pyrazinamide&Moxifloxacin -containing regimen

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• First Affiliated Hospital of Zhejiang University: lead

Related Publications (14)

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• Ito S, Yasuda M, Seike K, Sugawara T, Tsuchiya T, Yokoi S, Nakano M, Deguchi T. Clinical and microbiological outcomes in treatment of men with non-gonococcal urethritis with a 100-mg twice-daily dose regimen of sitafloxacin. J Infect Chemother. 2012 Jun;18(3):414-8. doi: 10.1007/s10156-012-0392-9. Epub 2012 Feb 28.

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Related Links

• WHO guideline

MeSH Terms

Conditions

Tuberculosis, Pulmonary

Interventions

sitafloxacin; Trimethoprim, Sulfamethoxazole Drug Combination; Rifampin; Pyrazinamide; rifapentine; Isoniazid; Ethambutol; Moxifloxacin

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Sulfamethoxazole; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Sulfanilamides; Aniline Compounds; Amines; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Trimethoprim; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Pyrazines; Hydrazines; Isonicotinic Acids; Acids, Heterocyclic; Pyridines; Ethylenediamines; Diamines; Polyamines; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof, MD

Study Record Dates

• First Submitted: June 17, 2022
• First Posted: July 12, 2022
• Study Start: October 1, 2022
• Primary Completion: June 30, 2025
• Study Completion (Estimated): June 30, 2026
• Last Updated: July 12, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will share