NCT03867136

Refining MDR-TB Treatment (T) Regimens (R) for Ultra(U) Short(S) Therapy(T)

Refining Multidrug Tuberculosis Treatment with the Ultra Short All Oral Regimen

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 354 (actual)
• Sponsor: Huashan Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to assess the efficacy, safety and tolerability of a combination of levofloxacin, linezolid, cycloserine and pyrazinamide (or clofazimine if resistant to pyrazinamide) treatments for 24 to 32 weeks (regimen consisted of clofazimine for 36\~44 weeks) in subjects with multidrug-resistant tuberculosis (MDR-TB) compared to WHO standardized shorter regimen of 36-44 weeks.

Detailed description

The TB-TRUST is a phaseIII, multicenter, open-label, randomized controlled trial. The purpose of this study is to assess the feasibility of the ultra-short treatment regimen of all-oral anti-TB drugs among selected MDR-TB patients who are susceptible to fluoroquinolones. A total of 354 participants with MDR-TB will be recruited and followed up until 84 weeks after randomization. During randomization, eligible patients will be assigned to in a 1:1 ratio to one of the following groups: The WHO standardized shorter regimen group and a PZA sensitivity guided ultra-short regimen group. WHO standardized shorter regimen group consists of 36-44 weeks with two phases of treatment. The first is an intensive phase of 16 weeks (extended up a maximum of 20 or 24 weeks in case of lack of smear conversion at the end of 16 or 20 weeks), and included moxifloxacin, amikacin, prothionamide, pyrazinamide, high-dose isoniazid, ethambutol, and clofazimine. This is followed by a continuation phase of 20 weeks with the following agents: moxifloxacin, pyrazinamide, ethambutol, and clofazimine. The PZA sensitivity guided ultra-short 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 levofloxacin, linezolid, cycloserine, pyrazinamide, and clofazimine. Then based on molecular PZA drug sensitivity results, patients will be in divided into two sub-groups: pyrazinamide-susceptible (PZA-S) patients and pyrazinamide-resistant (PZA-R) patients. The Regimen for PZA-S patients, consisting of levofloxacin, 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 levofloxacin, linezolid, cycloserine, and clofazimine given 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 compare the treatment success rate without relapse between the WHO standardized shorter regimen group and the PZA sensitivity guided ultra-short regimen group. The secondary objective is to compare the median time to sputum culture conversion. Safety evaluations performed are the routine lab tests, blood glucose, hearing, 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.

Conditions

• Multidrug Resistant Tuberculosis

Interventions

Type	Name	Description
DRUG	PZA sensitivity guided ultra-short all Oral Regimen	Pyrazinamide 1500 mg daily; Levofloxacin ≤50kg 500 mg daily, \>50kg 750mg daily; Linezolid: 600 mg daily; Cycloserine ≤50kg 500 mg daily, \>50kg 750mg daily; Clofazimine 100 mg daily; All treatment is taken daily;
DRUG	Standardized Shorter Regimen	Pyrazinamide 1500 mg daily;Levofloxacin 400 mg daily,; Prothionamide ≤50kg 500 mg daily, \>50kg 750mg daily; Ethambutol: ≤50kg 750 mg daily, \>50kg 1000mg daily; Clofazimine: 100 mg daily; Amikacin 600mg daily; High-dose isoniazid 600mg daily. All treatment is taken daily.

Timeline

• Start date: 2020-06-01
• Primary completion: 2024-08-10
• Completion: 2024-08-10
• First posted: 2019-03-07
• Last updated: 2024-11-12

Locations

13 sites across 1 country: China