Safety and Tolerability of Ultra-short Course Rifapentine and Isoniazid (1HP) for Prevention of Tuberculosis in HIV-Uninfected Individuals
超短疗程利福喷丁和异烟肼 (1HP) 用于预防未感染 HIV 个体结核病的安全性和耐受性
基本信息
- 批准号:10226377
- 负责人:
- 金额:$ 93.63万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-08-01 至 2025-05-31
- 项目状态:未结题
- 来源:
- 关键词:AdherenceAdolescentAdultAdverse eventBiologicalCause of DeathCenters for Disease Control and Prevention (U.S.)ChildClinical TrialsConsumptionCost AnalysisCost SavingsDataDevelopmentDisease modelDoseEpidemicEventExanthemaFeverGoalsGuidelinesHIVHIV InfectionsHIV SeronegativityHIV SeropositivityHepatotoxicityHypersensitivityImmunosuppressionIncidenceIndividualInterventionMeta-AnalysisModelingMonitorNational Institute of Allergy and Infectious DiseaseNausea and VomitingPatient Self-ReportPatientsPeripheral Nervous System DiseasesPharmaceutical PreparationsPharmacologyPopulationPopulations at RiskPreventionPreventive therapyPyrazinamideRandomizedRegimenResearchResearch PersonnelRifampinRifamycinsRiskSafetyStudy modelsSyndromeTherapy trialTimeToxic effectTuberculosisUnited States National Institutes of HealthWorkWorld Health Organizationbaseclinical practicecomparative cost effectivenesscostcost effectivenessdiscontinuation studyefficacy studyexperiencehigh riskhigh risk populationincremental cost-effectivenessinnovationisoniazidmortality riskmouse modelnovelpathogenpatient populationpillpreventrandomized trialrifapentineside effectsuccesstreatment comparisontrial comparinguptake
项目摘要
Project Summary
Tuberculosis (TB) is the leading infectious cause of death due to a single pathogen globally and the UN has
set ambitious targets for reducing the burden of TB by 2030. TB preventive therapy (TPT) is a critical
intervention for preventing TB disease and modeling studies consistently indicate that expanded TPT coverage
is essential for reaching UN targets. Implementation of TPT among the populations at risk remains extremely
poor, however, and new regimens that are shorter and safer than the decades-old standard of isoniazid
preventive therapy are urgently needed. Over the past several decades, we have pioneered the development
of short-course, rifamycin-based TPT. We demonstrated the efficacy of 3 months of weekly rifapentine and
isoniazid (3HP) in people with and without HIV infection and showed that it is non-inferior to longer courses of
isoniazid, with better adherence and less toxicity. This regimen is now recommended as a first-line treatment
for latent TB infection by the CDC and the World Health Organization, offering the potential of substantially
increased uptake of TPT as part of the END TB Strategy. More recently, supported by NIAID, we have shown
that one month of daily rifapentine and isoniazid (1HP) is non-inferior to nine months of isoniazid in people with
HIV infection, with higher completion rates and less toxicity. The availability of two innovative, new short-
course TPT regimens offers a transformative opportunity to global TB control. The potential of a one-month
regimen to catalyze uptake of TPT in high-risk populations is enormous, but data on its safety and tolerability in
people without HIV infection are needed.
The goal of this investigator-initiated, clinical trial application is to conduct a randomized trial comparing
treatment success rates and safety of 1HP and 3HP TPT regimens in high-risk patients without HIV infection.
While 3HP has been proved safe and effective in HIV-positive and –negative people, 1HP has only been
shown to be safe and efficacious in HIV-positive people. Efficacy of 1HP in non-HIV populations may be
inferred based on previous experience that shows comparability of TPT regimens across risk groups, but
toxicity and tolerability is not known. We will 1) compare treatment success with good adherence, documented
by self-report, pill count, and pharmacologic monitoring, of 1HP compared with 3HP in HIV-uninfected adults
and adolescents at increased risk of TB and 2) compare the safety of 1HP vs 3HP in this population. We
hypothesize that successful treatment with 1HP will be superior to 3HP, and that the safety and tolerability of
1HP will be superior to 3HP. We will also compare the cost-effectiveness of 1HP and 3HP using a societal
approach, modeling the incremental cost-effectiveness of 1HP vs 3HP, 6H, and no treatment. We hypothesize
that 1HP will be cost saving vs 3HP, vs modelled costs of 6H and v no TPT. The results of this trial will be
extremely valuable for establishing global and US guidelines for use of 1HP in HIV-negative people.
项目摘要
结核病(TB)是全球因单一病原体导致死亡的主要传染性原因,联合国已
制定了到2030年减少结核病负担的宏伟目标。结核病预防性治疗(TPT)是一项关键的
预防结核病干预措施和模型研究一致表明,扩大TPT覆盖率
是实现联合国目标的关键。在高危人群中实施TPT仍然是极端困难的。
然而,新的治疗方案比几十年前的异烟肼标准更短,更安全,
迫切需要预防性治疗。在过去的几十年里,我们率先开发了
短程利福霉素TPT我们证明了每周服用利福喷丁3个月的疗效,
异烟肼(3 HP)在有和没有艾滋病毒感染的人,并显示它是不劣于较长的疗程,
异烟肼,具有更好的粘附性和更低的毒性。目前推荐将此方案作为一线治疗方案
疾病预防控制中心和世界卫生组织对潜伏性结核病感染的研究,
作为结束结核病战略的一部分,增加了TPT的使用。最近,在NIAID的支持下,我们证明了
每日利福喷丁和异烟肼(1HP)1个月不劣于异烟肼9个月,
艾滋病毒感染,完成率较高,毒性较小。两个创新的,新的短-
TPT方案为全球结核病控制提供了变革性机会。一个月的潜力
在高危人群中催化TPT摄取的方案是巨大的,但关于其安全性和耐受性的数据,
需要没有艾滋病毒感染的人。
这项由制药商发起的临床试验申请的目标是进行一项随机试验,
1HP和3 HP TPT方案在无HIV感染的高危患者中的治疗成功率和安全性。
虽然3 HP已被证明是安全和有效的艾滋病毒阳性和阴性的人,
对HIV阳性者安全有效。1HP在非HIV人群中的疗效可能
根据既往经验推断,TPT方案在各风险组之间具有可比性,但
毒性和耐受性尚不清楚。我们将1)比较治疗成功与良好的依从性,记录
通过自我报告、药丸计数和药理学监测,与未感染HIV的成人中的3 HP相比,
和青少年结核病风险增加和2)比较1HP与3 HP在该人群中的安全性。我们
假设1HP成功治疗上级3 HP,且
1HP将上级3 HP。我们还将使用社会调查比较1HP和3 HP的成本效益。
方法,模拟1HP与3 HP、6 H和无治疗的增量成本效益。我们假设
1HP将比3 HP节省成本,比6 H的建模成本和无TPT节省成本。这次审判的结果将是
对于建立全球和美国HIV阴性人群使用1HP的指南非常有价值。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Richard E. Chaisson其他文献
Efficacy of Engineering Controls in Reducing Occupational Exposure to Aerosolized Pentamidine
- DOI:
10.1378/chest.102.6.1764 - 发表时间:
1992-12-01 - 期刊:
- 影响因子:
- 作者:
Melissa A. McDiarmid;John Schaefer;Cindy Lynn Richard;Richard E. Chaisson;Byron S. Tepper - 通讯作者:
Byron S. Tepper
The Impact of Prophylaxis on Outcome and Resource Utilization in <em>Pneumocystis carinii</em> Pneumonia
- DOI:
10.1378/chest.107.4.1018 - 发表时间:
1995-04-01 - 期刊:
- 影响因子:
- 作者:
Joel E. Gallant;Sharon M. McAvinue;Richard D. Moore;John G. Bartlett;David L. Stanton;Richard E. Chaisson - 通讯作者:
Richard E. Chaisson
Risk-stratified treatment for drug-susceptible pulmonary tuberculosis
药物敏感型肺结核的风险分层治疗
- DOI:
10.1038/s41467-024-53273-7 - 发表时间:
2024-10-30 - 期刊:
- 影响因子:15.700
- 作者:
Vincent K. Chang;Marjorie Z. Imperial;Patrick P. J. Phillips;Gustavo E. Velásquez;Payam Nahid;Andrew Vernon;Ekaterina V. Kurbatova;Susan Swindells;Richard E. Chaisson;Susan E. Dorman;John L. Johnson;Marc Weiner;Amina Jindani;Thomas Harrison;Erin E. Sizemore;William Whitworth;Wendy Carr;Kia E. Bryant;Deron Burton;Kelly E. Dooley;Melissa Engle;Pheona Nsubuga;Andreas H. Diacon;Nguyen Viet Nhung;Rodney Dawson;Radojka M. Savic - 通讯作者:
Radojka M. Savic
Tuberculosis Preventive Treatment in High TB-Burden Settings: A State-of-the-Art Review
- DOI:
10.1007/s40265-024-02131-3 - 发表时间:
2024-12-28 - 期刊:
- 影响因子:14.400
- 作者:
Violet Chihota;Makaita Gombe;Amita Gupta;Nicole Salazar-Austin;Tess Ryckman;Christopher J. Hoffmann;Sylvia LaCourse;Jyoti S. Mathad;Vidya Mave;Kelly E. Dooley;Richard E. Chaisson;Gavin Churchyard - 通讯作者:
Gavin Churchyard
Richard E. Chaisson的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Richard E. Chaisson', 18)}}的其他基金
JHU TRAC: Training and Supporting the Next Generation of TB Researchers
JHU TRAC:培训和支持下一代结核病研究人员
- 批准号:
10431020 - 财政年份:2022
- 资助金额:
$ 93.63万 - 项目类别:
JHU TRAC: Training and Supporting the Next Generation of TB Researchers
JHU TRAC:培训和支持下一代结核病研究人员
- 批准号:
10593142 - 财政年份:2022
- 资助金额:
$ 93.63万 - 项目类别:
The Johns Hopkins Center for AIDS Research (JHU CFAR)
约翰霍普金斯大学艾滋病研究中心 (JHU CFAR)
- 批准号:
10268586 - 财政年份:2020
- 资助金额:
$ 93.63万 - 项目类别:
Safety and Tolerability of Ultra-short Course Rifapentine and Isoniazid (1HP) for Prevention of Tuberculosis in HIV-Uninfected Individuals
超短疗程利福喷丁和异烟肼 (1HP) 用于预防未感染 HIV 个体结核病的安全性和耐受性
- 批准号:
10413161 - 财政年份:2020
- 资助金额:
$ 93.63万 - 项目类别:
Safety and Tolerability of Ultra-short Course Rifapentine and Isoniazid (1HP) for Prevention of Tuberculosis in HIV-Uninfected Individuals
超短疗程利福喷丁和异烟肼 (1HP) 用于预防 HIV 未感染者结核病的安全性和耐受性
- 批准号:
10631078 - 财政年份:2020
- 资助金额:
$ 93.63万 - 项目类别:
Safety and Tolerability of Ultra-short Course Rifapentine and Isoniazid (1HP) for Prevention of Tuberculosis in HIV-Uninfected Individuals
超短疗程利福喷丁和异烟肼 (1HP) 用于预防未感染 HIV 个体结核病的安全性和耐受性
- 批准号:
10018455 - 财政年份:2020
- 资助金额:
$ 93.63万 - 项目类别:
The Johns Hopkins Center for AIDS Research (JHU CFAR)
约翰霍普金斯大学艾滋病研究中心 (JHU CFAR)
- 批准号:
9322787 - 财政年份:2012
- 资助金额:
$ 93.63万 - 项目类别:
The Johns Hopkins Center for AIDS Research (JHU CFAR)
约翰霍普金斯大学艾滋病研究中心 (JHU CFAR)
- 批准号:
8843334 - 财政年份:2012
- 资助金额:
$ 93.63万 - 项目类别:
相似海外基金
Usefulness of a question prompt sheet for onco-fertility in adolescent and young adult patients under 25 years old.
问题提示表对于 25 岁以下青少年和年轻成年患者的肿瘤生育力的有用性。
- 批准号:
23K09542 - 财政年份:2023
- 资助金额:
$ 93.63万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
The impact of changes in social determinants of health on adolescent and young adult mental health during the COVID-19 pandemic: A longitudinal study of the Asenze cohort in South Africa
COVID-19 大流行期间健康社会决定因素的变化对青少年和年轻人心理健康的影响:南非 Asenze 队列的纵向研究
- 批准号:
10755168 - 财政年份:2023
- 资助金额:
$ 93.63万 - 项目类别:
A Priority Setting Partnership to Establish a Patient, Caregiver, and Clinician-identified Research Agenda for Adolescent and Young Adult Cancer in Canada
建立优先合作伙伴关系,以建立患者、护理人员和临床医生确定的加拿大青少年和年轻人癌症研究议程
- 批准号:
480840 - 财政年份:2023
- 资助金额:
$ 93.63万 - 项目类别:
Miscellaneous Programs
Incidence and Time on Onset of Cardiovascular Risk Factors and Cardiovascular Disease in Adult Survivors of Adolescent and Young Adult Cancer and Association with Exercise
青少年和青年癌症成年幸存者心血管危险因素和心血管疾病的发病率和时间以及与运动的关系
- 批准号:
10678157 - 财政年份:2023
- 资助金额:
$ 93.63万 - 项目类别:
Fertility experiences among ethnically diverse adolescent and young adult cancer survivors: A population-based study
不同种族青少年和年轻成年癌症幸存者的生育经历:一项基于人群的研究
- 批准号:
10744412 - 财政年份:2023
- 资助金额:
$ 93.63万 - 项目类别:
Treatment development for refractory leukemia using childhood/adolescent, and young adult leukemia biobank
利用儿童/青少年和青年白血病生物库开发难治性白血病的治疗方法
- 批准号:
23K07305 - 财政年份:2023
- 资助金额:
$ 93.63万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Molecular design of Two-Way Player CAR-T cells to overcome disease/antigen heterogeneity of childhood, adolescent, and young adult cancers
双向 CAR-T 细胞的分子设计,以克服儿童、青少年和年轻成人癌症的疾病/抗原异质性
- 批准号:
23H02874 - 财政年份:2023
- 资助金额:
$ 93.63万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Effects of adolescent social isolation on adult decision making and corticostriatal circuitry
青少年社会隔离对成人决策和皮质纹状体回路的影响
- 批准号:
10756652 - 财政年份:2023
- 资助金额:
$ 93.63万 - 项目类别:
Adolescent trauma produces enduring disruptions in sleep architecture that lead to increased risk for adult mental illness
青少年创伤会对睡眠结构产生持久的破坏,从而导致成人精神疾病的风险增加
- 批准号:
10730872 - 财政年份:2023
- 资助金额:
$ 93.63万 - 项目类别:
Using Tailored mHealth Strategies to Promote Weight Management among Adolescent and Young Adult Cancer Survivors
使用量身定制的移动健康策略促进青少年和年轻癌症幸存者的体重管理
- 批准号:
10650648 - 财政年份:2023
- 资助金额:
$ 93.63万 - 项目类别: