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Abstract：
BACKGROUND: An effective rifampicin-resistant tuberculosis (RR-TB) treatment regimen should include prevention of resistance amplification. While bedaquiline (BDQ) has been recommended in all-oral RR-TB treatment regimen since 2019, resistance is rising at alarming rates. This may be due to BDQ\'s delayed bactericidal effect, which increases the risk of selecting for resistance to fluoroquinolones and/or BDQ in the first week of treatment when the bacterial load is highest. We aim to strengthen the first week of treatment with the injectable drug amikacin (AMK). To limit the ototoxicity risk while maximising the bactericidal effect, we will evaluate the safety of adding a 30 mg/kg AMK injection on the first and fourth day of treatment.
METHODS: We will conduct a single-arm clinical trial on 20 RR-TB patients nested within an operational study called ShoRRT (All oral Shorter Treatment Regimen for Drug resistant Tuberculosis). In addition to all-oral RR-TB treatment, patients will receive two doses of AMK. The primary safety endpoint is any grade 3-4 adverse event during the first 2 weeks of treatment related to the use of AMK. With a sample size of 20 patients, we will have at least 80% statistical power to support the alternative hypothesis, indicating that less than 14% of patients treated with AMK experience a grade 3-4 adverse event related to its use. Safety data obtained from this study will inform a larger multicountry study on using two high doses of AMK to prevent acquired resistance.
BACKGROUND: Approval was obtained from the ethics committee of Rwanda, Rwanda Food and Drug Authority, Universitair Ziekenhuis, the Institute of Tropical Medicine ethics review board. All participants will provide informed consent. Study results will be disseminated through peer-reviewed journals and conferences.
BACKGROUND: NCT05555303.
METHODS: We will conduct a single-arm clinical trial on 20 RR-TB patients nested within an operational study called ShoRRT (All oral Shorter Treatment Regimen for Drug resistant Tuberculosis). In addition to all-oral RR-TB treatment, patients will receive two doses of AMK. The primary safety endpoint is any grade 3-4 adverse event during the first 2 weeks of treatment related to the use of AMK. With a sample size of 20 patients, we will have at least 80% statistical power to support the alternative hypothesis, indicating that less than 14% of patients treated with AMK experience a grade 3-4 adverse event related to its use. Safety data obtained from this study will inform a larger multicountry study on using two high doses of AMK to prevent acquired resistance.
BACKGROUND: Approval was obtained from the ethics committee of Rwanda, Rwanda Food and Drug Authority, Universitair Ziekenhuis, the Institute of Tropical Medicine ethics review board. All participants will provide informed consent. Study results will be disseminated through peer-reviewed journals and conferences.
BACKGROUND: NCT05555303.
摘要：
背景：有效的利福平耐药结核病（RR-TB）治疗方案应包括预防耐药性放大。虽然bedaquiline（BDQ）自2019年以来一直被推荐用于全口服RR-TB治疗方案，但耐药性正以惊人的速度上升。这可能是由于BDQ的延迟杀菌作用，这增加了在细菌载量最高的治疗第一周选择对氟喹诺酮类和/或BDQ耐药的风险。我们的目标是加强注射药物阿米卡星（AMK）的第一周治疗。为了限制耳毒性风险，同时最大化杀菌效果，我们将评估在治疗的第一天和第四天添加30mg/kgAMK注射液的安全性。
方法：我们将对20名RR-TB患者进行单臂临床试验，纳入一项名为ShoRRT（耐药结核病的所有口服短程治疗方案）的操作性研究。除了全口服RR-TB治疗，患者将接受两剂AMK。主要安全终点是在治疗的前2周内与使用AMK相关的任何3-4级不良事件。有20个病人的样本量,我们将有至少80%的统计能力来支持替代假设，这表明接受AMK治疗的患者中,少于14%的患者出现与使用AMK相关的3-4级不良事件.从这项研究中获得的安全性数据将为使用两种高剂量AMK预防获得性耐药性的更大的多国家研究提供信息。
背景：获得卢旺达伦理委员会的批准，卢旺达食品和药物管理局，齐肯胡斯大学，热带医学研究所伦理审查委员会。所有参与者将提供知情同意书。研究结果将通过同行评审的期刊和会议传播。
背景：NCT05555303。
方法：我们将对20名RR-TB患者进行单臂临床试验，纳入一项名为ShoRRT（耐药结核病的所有口服短程治疗方案）的操作性研究。除了全口服RR-TB治疗，患者将接受两剂AMK。主要安全终点是在治疗的前2周内与使用AMK相关的任何3-4级不良事件。有20个病人的样本量,我们将有至少80%的统计能力来支持替代假设，这表明接受AMK治疗的患者中,少于14%的患者出现与使用AMK相关的3-4级不良事件.从这项研究中获得的安全性数据将为使用两种高剂量AMK预防获得性耐药性的更大的多国家研究提供信息。
背景：获得卢旺达伦理委员会的批准，卢旺达食品和药物管理局，齐肯胡斯大学，热带医学研究所伦理审查委员会。所有参与者将提供知情同意书。研究结果将通过同行评审的期刊和会议传播。
背景：NCT05555303。
