Abstract:

Objective: Based on safety, tolerability, and preliminary clinical efficacy, this study was designed to develop a novel 3-month short-course five-drug combination regimen, B-P-L-S-Z (B, bedaquiline; P, pretomanid; L, linezolid; S, sitafloxacin; Z, pyrazinamide), and to investigate the early bactericidal activity (EBA) of sitafloxacin, so as to provide a basis for sample size estimation and trial design for the subsequent confirmatory clinical trial. Methods: A single-arm, open-label feasibility trial was conducted in 12 patients with bacteriologically confirmed rifampicin-resistant pulmonary tuberculosis treated at Beijing Chest Hospital, Capital Medical University, who were enrolled in accordance with the inclusion criteria. All patients first received oral sitafloxacin monotherapy for 7 consecutive days, followed by the B-P-L-S-Z regimen for 3 months (12 weeks). All subjects received medication under directly observed therapy with standardized health education. Drug safety and patient tolerability were assessed through adverse event monitoring, laboratory testing, electrocardiographic changes, and treatment outcomes. Clinical efficacy was evaluated by the sputum culture conversion rate at the end of treatment, the time to culture conversion, and the disease relapse rate during the 78-week follow-up period after treatment completion. Discussion: If the short-course B-P-L-S-Z combination regimen proves to be clinically feasible, the findings of this study will provide an important reference for the design and implementation of subsequent randomized controlled clinical trials.

Key words: Tuberculosis, Rifampicin, Drug resistance, Clinical protocols, Feasibility studies