保护家庭接触新诊断指数耐多药结核病患者:PHOENIx 3期临床试验的研究方案。

IF 1.9 3区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL
Michelle A. Kendall , Michael D. Hughes , Soyeon Kim , Lisa A. Aaron , Linda Naini , Nishi Suryavanshi , N. Sarita Shah , Vanessa Rouzier , Jeffrey Hafkin , Thucuma Sise , Justine Beck , Barbara E. Heckman , Jessica E. Haberer , Mark Harrington , Kimberly K. Scarsi , Anneke C. Hesseling , Susan Swindells , Gavin J. Churchyard , Amita Gupta
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引用次数: 0

摘要

导言:指导耐多药结核病(MDR-TB)患者密切接触者结核病预防治疗(TPT)的数据有限。虽然以左氧氟沙星为基础的TPT已被证明是安全和有效的,但对于那些暴露于耐氟喹诺酮结核分枝杆菌(M. tb)的人来说,需要替代方案。PHOENIx试验评估了在耐多药结核病患者的高危家庭接触者(hhc)中使用一种新型硝基咪唑(delamanid)是否能降低他们患活动性结核病的风险。方法/设计:PHOENIx是一项3期、开放标签、多中心临床试验,采用集群随机优势设计(家庭组成集群)。该研究的目的是比较26 周delamanid和异烟肼在96 周随访期间预防肺部耐多药结核病成人HHCs确诊或可能结核病的疗效和安全性。讨论:预防耐多药结核病是全球优先事项。由于氟喹诺酮类药物耐药性日益增加,需要以左氧氟沙星为基础的TPT的替代品。PHOENIx是一项评估delamanid的3期试验,将为世卫组织指南提供信息。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Protecting households on exposure to newly diagnosed index multidrug-resistant tuberculosis patients: Study protocol for the PHOENIx phase 3 clinical trial

Introduction

Data to guide tuberculosis (TB) preventive treatment (TPT) of close contacts of people with multidrug-resistant tuberculosis (MDR-TB) are limited. While levofloxacin-based TPT has been shown safe and efficacious, alternatives are needed for those exposed to fluoroquinolone-resistant Mycobacterium tuberculosis (M. tb). The PHOENIx trial evaluates whether using a novel nitroimidazole, delamanid, in high-risk household contacts (HHCs) of patients with MDR-TB reduces their risk of developing active TB.

Methods/Design

PHOENIx is a phase 3, open-label, multicenter clinical trial with a cluster-randomized superiority design (households form the clusters). The study objectives are to compare efficacy and safety of 26 weeks of delamanid versus isoniazid for preventing confirmed or probable TB during 96 weeks of follow-up among HHCs of adults with pulmonary MDR-TB. HHCs are defined as young children <5 years, people living with HIV or non-HIV immunosuppression, or people with evidence of M. tb infection. The study was originally designed to enroll 3452 HHCs to provide 90 % power to detect a 50 % reduction in the cumulative proportion of HHCs developing confirmed or probable TB during 96 weeks of follow-up from 5 % in the isoniazid arm to 2.5 % in the delamanid arm. The design included a sample size re-evaluation to address uncertainty in study design assumptions.

Discussion

Preventing MDR-TB is a global priority. Alternatives to levofloxacin-based TPT are needed since fluoroquinolone resistance is growing. PHOENIx, a phase 3 trial evaluating delamanid, is poised to inform WHO guidelines.
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来源期刊
CiteScore
3.70
自引率
4.50%
发文量
281
审稿时长
44 days
期刊介绍: Contemporary Clinical Trials is an international peer reviewed journal that publishes manuscripts pertaining to all aspects of clinical trials, including, but not limited to, design, conduct, analysis, regulation and ethics. Manuscripts submitted should appeal to a readership drawn from disciplines including medicine, biostatistics, epidemiology, computer science, management science, behavioural science, pharmaceutical science, and bioethics. Full-length papers and short communications not exceeding 1,500 words, as well as systemic reviews of clinical trials and methodologies will be published. Perspectives/commentaries on current issues and the impact of clinical trials on the practice of medicine and health policy are also welcome.
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