Clinic and Research Centre of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People's Republic of China.
Department of Mechanical and Aerospace Engineering, University of California, Los Angeles, CA, USA.
Emerg Microbes Infect. 2023 Dec;12(1):2187247. doi: 10.1080/22221751.2023.2187247.
In preclinical studies, a new antituberculosis drug regimen markedly reduced the time required to achieve relapse-free cure. This study aimed to preliminarily evaluate the efficacy and safety of this four-month regimen, consisting of clofazimine, prothionamide, pyrazinamide and ethambutol, with a standard six-month regimen in patients with drug-susceptible tuberculosis. An open-label pilot randomized clinical trial was conducted among the patients with newly diagnosed bacteriologically-confirmed pulmonary tuberculosis. The primary efficacy end-point was sputum culture negative conversion. Totally, 93 patients were included in the modified intention-to-treat population. The rates of sputum culture conversion were 65.2% (30/46) and 87.2% (41/47) for short-course and standard regimen group, respectively. There was no difference on two-month culture conversion rates, time to culture conversion, nor early bactericidal activity (> 0.05). However, patients on short-course regimen were observed with lower rates of radiological improvement or recovery and sustained treatment success, which was mainly attributed to higher percent of patients permanently changed assigned regimen (32.1% vs. 12.3%, = 0.012). The main cause for it was drug-induced hepatitis (16/17). Although lowering the dose of prothionamide was approved, the alternative option of changing assigned regimen was chosen in this study. While in per-protocol population, sputum culture conversion rates were 87.0% (20/23) and 94.4% (34/36) for the respective groups. Overall, the short-course regimen appeared to have inferior efficacy and higher incidence of hepatitis but desired efficacy in per-protocol population. It provides the first proof-of-concept in humans of the capacity of the short-course approach to identify drug regimens that can shorten the treatment time for tuberculosis.
在临床前研究中，一种新的抗结核药物方案显著缩短了达到无复发治愈所需的时间。本研究旨在初步评估该为期四个月的方案（包含氯法齐明、丙硫异烟胺、吡嗪酰胺和乙胺丁醇）与标准的六个月方案在药物敏感肺结核患者中的疗效和安全性。这是一项开放性标签的试点随机临床试验，纳入了新诊断的细菌学确诊肺结核患者。主要疗效终点是痰培养转阴。共有 93 例患者纳入改良意向治疗人群。短程组和标准组的痰培养转阴率分别为 65.2%（30/46）和 87.2%（41/47）。两组在两个月培养转换率、培养转换时间和早期杀菌活性（>0.05）方面无差异。然而，短程组患者的影像学改善或恢复率和持续治疗成功率较低，这主要归因于永久更改方案的患者比例较高（32.1%比 12.3%，=0.012）。主要原因是药物性肝炎（16/17）。尽管批准降低丙硫异烟胺的剂量，但本研究选择了更改方案的替代方案。而在符合方案人群中，两组的痰培养转阴率分别为 87.0%（20/23）和 94.4%（34/36）。总的来说，短程方案的疗效较差，肝炎发生率较高，但符合方案人群的疗效理想。这为缩短结核病治疗时间的短程方法识别药物方案的能力提供了人体的首个概念验证。
