The purpose of this study is to assess the efficacy, safety and tolerability of a combination of bedaquiline, linezolid, cycloserine, clofazimine and pyrazinamide treatments guided by PZA sensitivity for 24 to 36 weeks in subjects with fluoroquinolone-resistant MDR-TB .
The TB-TRUST-plus is a phaseIII, multicenter, open-label trial. The purpose of this study is to assess the feasibility of the ultra-short treatment regimen guided by PZA sensitivity among fluoroquinolone-resistant MDR-TB patients.A total of 200 participants with MDR-TB will be recruited and followed up until 84 weeks after the treatment initiation. This regimen consists of two periods of 24-36 weeks. During the first 4-8 weeks(waiting for pyrazinamide drug sensitivity test), the regimen consists of bedaquiline, linezolid, cycloserine, clofazimine and pyrazinamide. Then based on molecular PZA drug sensitivity results, patients will be in divided into 3 sub-groups: pyrazinamide-susceptible (PZA-S) patients , pyrazinamide-resistant (PZA-R) patients and pyrazinamide-unavailable (PZA-U)patients. The Regimen for PZA-S patients, consisting of bedaquiline, linezolid, cycloserine and pyrazinamide, are given until the 24th week (prolonged to 28 or 32 weeks if no smear conversion by end of 16th and 20th week). PZA-R sub-group regimen, consisting of bedaquiline, linezolid, cycloserine and clofazimine ,are given until 36th week (prolonged to 40 or 44 weeks if no smear conversion by end of 16th and 20th week) . PZA-U sub-group continue the previous regimen, consisting of bedaquiline, linezolid, cycloserine , clofazimine and pyrazinamide ,until 36th week (prolonged to 40 or 44 weeks if no smear conversion by end of 16th and 20th week) . The primary objective is to access the treatment success rate without relapse of the PZA sensitivity guided ultra short regimen. The secondary objective is to access the median time to sputum culture conversion. Safety evaluations performed are the routine lab tests, blood glucose, vital signs, electrocardiograph (ECG), reporting of adverse events, peripheral neuropathy brief examining with the use of a Brief Peripheral Neuropathy rating scale(BPNS) and ophthalmologic examination, including assessment of visual acuity and color vision,physical examinations and chest CT. Adverse events will be monitored and promptly managed during the whole treatment course.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
89
400 mg once daily for 2 weeks then 200mg 3 times per week;
1500 mg daily
600 mg daily
The Third People's Hospital of Shenzhen City
Shenzhen, Guangzhou, China
Guiyang Public Health Treatment Center
Guizhou, Guizhou, China
The Sixth People's Hospital of Zhengzhou
Treatment success rate
To access the treatment success rate without relapse .Treatment outcomes will be classified into favourable outcome and unfavourable outcome.
Time frame: 84 weeks after the treatment initiation
The median time to Sputum Culture Conversion
time from treatment initiation to the first of two consecutive negative sputum cultures without an intervening positive culture in liquid media
Time frame: Time Frame: 12-36 weeks after treatment initiation
The frequency of grade 3 or greater adverse events among patients
to access the proportion of patients who experience grade 3 or greater adverse events (graded according to the Division of AIDS severity criteria for adverse events) during treatment or follow-up;
Time frame: 84 weeks after treatment initiation
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≤50kg 500 mg daily, \>50kg 750mg daily;
100 mg daily;
Zhengzhou, Henan, China
Hunan Chest Hospital
Changsha, Hunan, China
Huaihua first people's Hospital
Huaihua, Hunan, China
Huashan Hospital of Fudan University
Shanghai, Shanghai Municipality, China
Shanxi Provincial Tuberculosis Control Institute
Xi’an, Shanxi, China
Chest Hospitalof Xinjiang Uygur Autonomous Region of PRC
Ürümqi, Xinjiang, China
Baoshan People's Hospital
Baoshan, Yunnan, China
Yunnan Provincial Infectious Disease Hospital
Kunming, Yunnan, China
...and 5 more locations