Efficacy and safety of an innovative short-course regimen containing clofazimine for treatment of drug-susceptible tuberculosis: a clinical trial
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, w...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Emerging Microbes and Infections |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2023.2187247 |
| _version_ | 1797652824853577728 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Xubin Zheng |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T16:35:29Z |
| format | Article |
| id | doaj.art-bcc7bcb8469149d9a4e7a3b5d77c9834 |
| institution | Directory Open Access Journal |
| issn | 2222-1751 |
| language | English |
| last_indexed | 2024-03-11T16:35:29Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj.art-bcc7bcb8469149d9a4e7a3b5d77c98342023-10-23T17:36:54ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512023-12-0112110.1080/22221751.2023.2187247Efficacy and safety of an innovative short-course regimen containing clofazimine for treatment of drug-susceptible tuberculosis: a clinical trialXubin Zheng0Xuwei Gui1Lan Yao2Jun Ma3Yifan He4Hai Lou5Jin Gu6Ruoyan Ying7Liping Chen8Qin Sun9Yidian Liu10Chih-Ming Ho11Bai-Yu Lee12Daniel L. Clemens13Marcus A. Horwitz14Xianting Ding15Xiaohui Hao16Hua Yang17Wei Sha18Clinic and Research Centre of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of ChinaClinic and Research Centre of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of ChinaClinic and Research Centre of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of ChinaClinic and Research Centre of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of ChinaClinic and Research Centre of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of ChinaClinic and Research Centre of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of ChinaClinic and Research Centre of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of ChinaClinic and Research Centre of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of ChinaClinic and Research Centre of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of ChinaClinic and Research Centre of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of ChinaClinic and Research Centre of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of ChinaDepartment of Mechanical and Aerospace Engineering, University of California, Los Angeles, CA, USADivision of Infectious Diseases, Department of Medicine, University of California, Los Angeles, CA, USADivision of Infectious Diseases, Department of Medicine, University of California, Los Angeles, CA, USADivision of Infectious Diseases, Department of Medicine, University of California, Los Angeles, CA, USAInstitute for Personalized Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, People’s Republic of ChinaClinic and Research Centre of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of ChinaClinic and Research Centre of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of ChinaClinic and Research Centre of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of ChinaABSTRACTIn 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.https://www.tandfonline.com/doi/10.1080/22221751.2023.2187247Short-course treatmentclofazimineparabolic response surfacepulmonary tuberculosisrandomized clinical trial |
| spellingShingle | 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 Efficacy and safety of an innovative short-course regimen containing clofazimine for treatment of drug-susceptible tuberculosis: a clinical trial Emerging Microbes and Infections Short-course treatment clofazimine parabolic response surface pulmonary tuberculosis randomized clinical trial |
| title | Efficacy and safety of an innovative short-course regimen containing clofazimine for treatment of drug-susceptible tuberculosis: a clinical trial |
| title_full | Efficacy and safety of an innovative short-course regimen containing clofazimine for treatment of drug-susceptible tuberculosis: a clinical trial |
| title_fullStr | Efficacy and safety of an innovative short-course regimen containing clofazimine for treatment of drug-susceptible tuberculosis: a clinical trial |
| title_full_unstemmed | Efficacy and safety of an innovative short-course regimen containing clofazimine for treatment of drug-susceptible tuberculosis: a clinical trial |
| title_short | Efficacy and safety of an innovative short-course regimen containing clofazimine for treatment of drug-susceptible tuberculosis: a clinical trial |
| title_sort | efficacy and safety of an innovative short course regimen containing clofazimine for treatment of drug susceptible tuberculosis a clinical trial |
| topic | Short-course treatment clofazimine parabolic response surface pulmonary tuberculosis randomized clinical trial |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2023.2187247 |
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