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
{"title":"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。","authors":"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","doi":"10.1016/j.cct.2025.108084","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><div>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 <em>Mycobacterium tuberculosis (M. tb)</em>. 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.</div></div><div><h3>Methods/Design</h3><div>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 <em>M. tb</em> 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.</div></div><div><h3>Discussion</h3><div>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.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"158 ","pages":"Article 108084"},"PeriodicalIF":1.9000,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Protecting households on exposure to newly diagnosed index multidrug-resistant tuberculosis patients: Study protocol for the PHOENIx phase 3 clinical trial\",\"authors\":\"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\",\"doi\":\"10.1016/j.cct.2025.108084\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Introduction</h3><div>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 <em>Mycobacterium tuberculosis (M. tb)</em>. 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.</div></div><div><h3>Methods/Design</h3><div>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 <em>M. tb</em> 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.</div></div><div><h3>Discussion</h3><div>Preventing MDR-TB is a global priority. Alternatives to levofloxacin-based TPT are needed since fluoroquinolone resistance is growing. 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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.
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.