Efficacy and safety of an innovative short-course regimen containing clofazimine for treatment of drug-susceptible tuberculosis: a clinical trial

Xubin Zheng; Xuwei Gui; Lan Yao; Jun Ma; Yifan He; Hai Lou; Jin Gu; Ruoyan Ying; Liping Chen; Qin Sun; Yidian Liu; Chih-Ming Ho; Bai-Yu Lee; Daniel L. Clemens; Marcus A. Horwitz; Xianting Ding; Xiaohui Hao; Hua Yang; Wei Sha

doi:10.1080/22221751.2023.2187247

Emerging Microbes and Infections (Dec 2023)

Efficacy and safety of an innovative short-course regimen containing clofazimine for treatment of drug-susceptible tuberculosis: a clinical trial

Xubin Zheng,
Xuwei Gui,
Lan Yao,
Jun Ma,
Yifan He,
Hai Lou,
Jin Gu,
Ruoyan Ying,
Liping Chen,
Qin Sun,
Yidian Liu,
Chih-Ming Ho,
Bai-Yu Lee,
Daniel L. Clemens,
Marcus A. Horwitz,
Xianting Ding,
Xiaohui Hao,
Hua Yang,
Wei Sha

Affiliations

Xubin Zheng: Clinic and Research Centre of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of China
Xuwei Gui: Clinic and Research Centre of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of China
Lan Yao: Clinic and Research Centre of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of China
Jun Ma: Clinic and Research Centre of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of China
Yifan He: Clinic and Research Centre of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of China
Hai Lou: Clinic and Research Centre of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of China
Jin Gu: Clinic and Research Centre of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of China
Ruoyan Ying: Clinic and Research Centre of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of China
Liping Chen: Clinic and Research Centre of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of China
Qin Sun: Clinic and Research Centre of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of China
Yidian Liu: Clinic and Research Centre of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of China
Chih-Ming Ho: Department of Mechanical and Aerospace Engineering, University of California, Los Angeles, CA, USA
Bai-Yu Lee: Division of Infectious Diseases, Department of Medicine, University of California, Los Angeles, CA, USA
Daniel L. Clemens: Division of Infectious Diseases, Department of Medicine, University of California, Los Angeles, CA, USA
Marcus A. Horwitz: Division of Infectious Diseases, Department of Medicine, University of California, Los Angeles, CA, USA
Xianting Ding: Institute for Personalized Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, People’s Republic of China
Xiaohui Hao: Clinic and Research Centre of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of China
Hua Yang: Clinic and Research Centre of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of China
Wei Sha: Clinic and Research Centre of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of China

DOI: https://doi.org/10.1080/22221751.2023.2187247
Journal volume & issue: Vol. 12, no. 1

Abstract

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ABSTRACTIn 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 (P > 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%, P = 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.

Published in Emerging Microbes and Infections

ISSN: 2222-1751 (Online)
Publisher: Taylor & Francis Group
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Infectious and parasitic diseases; Science: Microbiology
Website: https://www.tandfonline.com/journals/temi

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