Sitafloxacin-containing Regimens for Shortening Tuberculosis Treatment

NCT ID: NCT05454345

Last Updated: 2022-07-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

620 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-10-01

Study Completion Date

2026-06-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Tuberculosis, Pulmonary

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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

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

Group Type EXPERIMENTAL

Sitafloxacin

Intervention Type DRUG

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

Pyrazinamide

Intervention Type DRUG

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

Rifapentine

Intervention Type DRUG

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

Isoniazid

Intervention Type DRUG

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

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.

Group Type EXPERIMENTAL

Sitafloxacin

Intervention Type DRUG

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

SMZ/TMP

Intervention Type 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

Pyrazinamide

Intervention Type DRUG

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

Rifapentine

Intervention Type DRUG

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

Isoniazid

Intervention Type DRUG

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

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.

Group Type ACTIVE_COMPARATOR

Rifampin

Intervention Type DRUG

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

Pyrazinamide

Intervention Type DRUG

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

Isoniazid

Intervention Type DRUG

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

Ethambutol

Intervention Type 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

Eight weeks of daily treatment with rifapentine, isoniazid, pyrazinamide, and moxifloxacin, followed by Nine weeks of daily treatment with rifapentine, isoniazid, and moxifloxacin.

Group Type ACTIVE_COMPARATOR

Rifapentine

Intervention Type DRUG

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

Isoniazid

Intervention Type DRUG

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

Ethambutol

Intervention Type DRUG

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

Moxifloxacin

Intervention Type DRUG

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

Interventions

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Sitafloxacin

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

Intervention Type 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

Intervention Type DRUG

Rifampin

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

Intervention Type DRUG

Pyrazinamide

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

Intervention Type DRUG

Rifapentine

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

Intervention Type DRUG

Isoniazid

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

Intervention Type DRUG

Ethambutol

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

Intervention Type 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)

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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First Affiliated Hospital of Zhejiang University

OTHER

Sponsor Role lead

Responsible Party

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Zhang Ying

Prof, MD

Responsibility Role PRINCIPAL_INVESTIGATOR

References

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Guidelines for the Programmatic Management of Drug-Resistant Tuberculosis: 2011 Update. Geneva: World Health Organization; 2011. Available from http://www.ncbi.nlm.nih.gov/books/NBK148644/

Reference Type BACKGROUND
PMID: 23844450 (View on PubMed)

Gupta VK, Kumar MM, Singh D, Bisht D, Sharma S. Drug targets in dormant Mycobacterium tuberculosis: can the conquest against tuberculosis become a reality? Infect Dis (Lond). 2018 Feb;50(2):81-94. doi: 10.1080/23744235.2017.1377346. Epub 2017 Sep 21.

Reference Type BACKGROUND
PMID: 28933243 (View on PubMed)

Burman WJ, Gallicano K, Peloquin C. Comparative pharmacokinetics and pharmacodynamics of the rifamycin antibacterials. Clin Pharmacokinet. 2001;40(5):327-41. doi: 10.2165/00003088-200140050-00002.

Reference Type BACKGROUND
PMID: 11432536 (View on PubMed)

Dorman SE, Nahid P, Kurbatova EV, Phillips PPJ, Bryant K, Dooley KE, Engle M, Goldberg SV, Phan HTT, Hakim J, Johnson JL, Lourens M, Martinson NA, Muzanyi G, Narunsky K, Nerette S, Nguyen NV, Pham TH, Pierre S, Purfield AE, Samaneka W, Savic RM, Sanne I, Scott NA, Shenje J, Sizemore E, Vernon A, Waja Z, Weiner M, Swindells S, Chaisson RE; AIDS Clinical Trials Group; Tuberculosis Trials Consortium. Four-Month Rifapentine Regimens with or without Moxifloxacin for Tuberculosis. N Engl J Med. 2021 May 6;384(18):1705-1718. doi: 10.1056/NEJMoa2033400.

Reference Type BACKGROUND
PMID: 33951360 (View on PubMed)

Keating GM. Sitafloxacin: in bacterial infections. Drugs. 2011 Apr 16;71(6):731-44. doi: 10.2165/11207380-000000000-00000.

Reference Type BACKGROUND
PMID: 21504249 (View on PubMed)

Yamaguchi K, Ohno A, Ishii Y, Tateda K, Iwata M, Kanda M, Akizawa K, Shimizu C, Kon S, Nakamura K, Matsuda K, Tominaga M, Nakagawa T, Sugita A, Ito T, Kato J, Suwabe A, Yamahata K, Kawamura C, Tashiro H, Horiuchi H, Katayama Y, Kondou S, Misawa S, Murata M, Kobayashi Y, Okamoto H, Yamazaki K, Okada M, Haruki K, Kanno H, Aihara M, Maesaki S, Hashikita G, Miyajima E, Sumitomo M, Saito T, Yamane N, Kawashima C, Akiyama T, Ieiri T, Yamamoto Y, Okamoto Y, Okabe H, Moro K, Shigeta M, Yoshida H, Yamashita M, Hida Y, Takubo T, Kusakabe T, Masaki H, Heijyou H, Nakaya H, Kawahara K, Sano R, Matsuo S, Kono H, Yuzuki Y, Ikeda N, Idomuki M, Soma M, Yamamoto G, Kinoshita S, Kawano S, Oka M, Kusano N, Kang D, Ono J, Yasujima M, Miki M, Hayashi M, Okubo S, Toyoshima S, Kaku M, Sekine I, Shiotani J, Horiuchi H, Tazawa Y, Yoneyama A, Kumasaka K, Koike K, Taniguchi N, Ozaki Y, Uchida T, Murakami M, Inuzuka K, Gonda H, Yamaguchi I, fujimoto Y, Iriyama J, Asano Y, Genma H, Maekawa M, Yoshimura H, Nakatani K, Baba H, Ichiyama S, Fujita S, Kuwabara M, Okazaki T, Fujiwara H, Ota H, Nagai A, Fujita J, Negayama K, Sugiura T, Kamioka M, Murase M, Yamane N, Nakasone I, Okayama A, Aoki Y, Kusaba K, Nakashima Y, Miyanohara H, Hiramatsu K, Saikawa T, Yanagihara K, Matsuda J, Kohno S, Mashiba K. [In vitro susceptibilities to levofloxacin and various antibacterial agents of 12,919 clinical isolates obtained from 72 centers in 2007]. Jpn J Antibiot. 2009 Aug;62(4):346-70. Japanese.

Reference Type BACKGROUND
PMID: 19860322 (View on PubMed)

Asakura T, Suzuki S, Fukano H, Okamori S, Kusumoto T, Uwamino Y, Ogawa T, So M, Uno S, Namkoong H, Yoshida M, Kamata H, Ishii M, Nishimura T, Hoshino Y, Hasegawa N. Sitafloxacin-Containing Regimen for the Treatment of Refractory Mycobacterium avium Complex Lung Disease. Open Forum Infect Dis. 2019 Mar 7;6(4):ofz108. doi: 10.1093/ofid/ofz108. eCollection 2019 Apr.

Reference Type BACKGROUND
PMID: 31111076 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22370921 (View on PubMed)

Mori H, Suzuki H, Matsuzaki J, Masaoka T, Kanai T. 10-Year Trends in Helicobacter pylori Eradication Rates by Sitafloxacin-Based Third-Line Rescue Therapy. Digestion. 2020;101(5):644-650. doi: 10.1159/000501610. Epub 2019 Aug 6.

Reference Type BACKGROUND
PMID: 31387107 (View on PubMed)

Li Y, Zhu D, Peng Y, Tong Z, Ma Z, Xu J, Sun S, Tang H, Xiu Q, Liang Y, Wang X, Lv X, Dai Y, Zhu Y, Qu Y, Xu K, Huang Y, Wu S, Lai G, Li X, Han X, Yang Z, Sheng J, Liu Z, Li H, Chen Y, Zhu H, Zhang Y. A randomized, controlled, multicenter clinical trial to evaluate the efficacy and safety of oral sitafloxacin versus moxifloxacin in adult patients with community-acquired pneumonia. Curr Med Res Opin. 2021 Apr;37(4):693-701. doi: 10.1080/03007995.2021.1885362. Epub 2021 Feb 22.

Reference Type BACKGROUND
PMID: 33534617 (View on PubMed)

Leechawengwongs M, Prammananan T, Jaitrong S, Billamas P, Makhao N, Thamnongdee N, Thanormchat A, Phurattanakornkul A, Rattanarangsee S, Ratanajaraya C, Disratthakit A, Chaiprasert A. In Vitro Activity and MIC of Sitafloxacin against Multidrug-Resistant and Extensively Drug-Resistant Mycobacterium tuberculosis Isolated in Thailand. Antimicrob Agents Chemother. 2017 Dec 21;62(1):e00825-17. doi: 10.1128/AAC.00825-17. Print 2018 Jan.

Reference Type BACKGROUND
PMID: 29061759 (View on PubMed)

Kamada K, Yoshida A, Iguchi S, Arai Y, Uzawa Y, Konno S, Shimojima M, Kikuchi K. Nationwide surveillance of antimicrobial susceptibility of 509 rapidly growing mycobacteria strains isolated from clinical specimens in Japan. Sci Rep. 2021 Jun 9;11(1):12208. doi: 10.1038/s41598-021-91757-4.

Reference Type BACKGROUND
PMID: 34108590 (View on PubMed)

Yi L, Aono A, Chikamatsu K, Igarashi Y, Yamada H, Takaki A, Mitarai S. In vitro activity of sitafloxacin against Mycobacterium tuberculosis with gyrA/B mutations isolated in Japan. J Med Microbiol. 2017 Jun;66(6):770-776. doi: 10.1099/jmm.0.000493.

Reference Type BACKGROUND
PMID: 28598311 (View on PubMed)

Suzuki Y, Nakajima C, Tamaru A, Kim H, Matsuba T, Saito H. Sensitivities of ciprofloxacin-resistant Mycobacterium tuberculosis clinical isolates to fluoroquinolones: role of mutant DNA gyrase subunits in drug resistance. Int J Antimicrob Agents. 2012 May;39(5):435-9. doi: 10.1016/j.ijantimicag.2012.01.007. Epub 2012 Mar 13.

Reference Type BACKGROUND
PMID: 22421328 (View on PubMed)

Related Links

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Other Identifiers

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yzhang207

Identifier Type: -

Identifier Source: org_study_id

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