背景:对氟喹诺酮耐药的耐多药/利福平耐药结核病(XDR前结核病)的治疗通常比耐药性较低的菌株的治疗持续时间更长,产生更差的疗效结果,并导致严重的毒性。较新的抗结核药物,bedaquiline和delamanid,和重新利用的药物氯法齐明和利奈唑胺,显示出更短的组合的巨大希望,毒性较小,和有效的方案。迄今为止,没有随机化,内部和同时控制的较短的试验,包含这些更新和重新利用的药物的全口服方案足以为XDR前TB患者产生结果。
方法:endTB-Q是第三阶段,多国,随机化,控制,平行,评估XDR前结核病患者治疗策略的有效性和安全性的开放标签临床试验.研究参与者以2:1的比例随机分配到实验或对照组,分别。实验臂包含bedaquiline,利奈唑胺,氯法齐明,还有Delamanid.该对照包括WHO对XDR前结核病的同期护理标准。实验手臂持续时间由基线涂片显微镜和胸部X线成像的复合确定,并在6个月时使用痰培养结果进行重新评估:疾病较不广泛的参与者接受6个月,疾病较广泛的参与者接受9个月的治疗。随机化按国家和根据筛选/基线特征定义的参与者TB疾病表型程度进行分层。研究参与在随机化后持续长达104周。主要目的是评估实验方案在73周时的疗效是否不劣于对照。2个手臂的324个参与者的样本量至少提供了80%的权力来显示非劣性,单侧α为0.025,非劣效性为12%,在修改后的意向治疗和符合方案的人群中,均与对照组相反。
结论:这项针对XDR前结核病缩短治疗的内部对照研究将为围绕使用四种药物治疗XDR前结核病的临床和政策决策提供迫切需要的数据和证据。全口,缩短方案。
背景:临床试验。政府NCT03896685。2018年4月1日注册;该记录最后一次更新为2023年3月17日的4.3版研究方案。
BACKGROUND: Treatment for fluoroquinolone-resistant multidrug-resistant/rifampicin-resistant tuberculosis (pre-XDR TB) often lasts longer than treatment for less resistant strains, yields worse efficacy results, and causes substantial toxicity. The newer anti-tuberculosis drugs,
bedaquiline and delamanid, and repurposed drugs clofazimine and linezolid, show great promise for combination in shorter, less-toxic, and effective regimens. To date, there has been no randomized, internally and concurrently controlled
trial of a shorter, all-oral regimen comprising these newer and repurposed drugs sufficiently powered to produce results for pre-XDR TB patients.
METHODS: endTB-Q is a phase III, multi-country, randomized, controlled, parallel, open-label clinical
trial evaluating the efficacy and safety of a treatment strategy for patients with pre-XDR TB. Study participants are randomized 2:1 to experimental or control arms, respectively. The experimental arm contains
bedaquiline, linezolid, clofazimine, and delamanid. The control comprises the contemporaneous WHO standard of care for pre-XDR TB. Experimental arm duration is determined by a composite of smear microscopy and chest radiographic imaging at baseline and re-evaluated at 6 months using sputum culture results: participants with less extensive disease receive 6 months and participants with more extensive disease receive 9 months of treatment. Randomization is stratified by country and by participant extent-of-TB-disease phenotype defined according to screening/baseline characteristics.
Study participation lasts up to 104 weeks post randomization. The primary objective is to assess whether the efficacy of experimental regimens at 73 weeks is non-inferior to that of the control. A sample size of 324 participants across 2 arms affords at least 80% power to show the non-inferiority, with a one-sided alpha of 0.025 and a non-inferiority margin of 12%, against the control in both modified intention-to-treat and per-protocol populations.
CONCLUSIONS: This internally controlled study of shortened treatment for pre-XDR TB will provide urgently needed data and evidence for clinical and policy decision-making around the treatment of pre-XDR TB with a four-drug, all-oral, shortened regimen.
BACKGROUND: ClinicalTrials.Gov NCT03896685. Registered on 1 April 2018; the record was last updated for study protocol version 4.3 on 17 March 2023.