Phase 4 Operational Study to Assess the Effectiveness, Feasibility, Acceptability, and Cost-effectiveness of the GeneXpert MTB/XDR (Xpert XDR; Cepheid) Assay for Rapid Triage-and-treatment of DR-TB
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 786
- 试验地点
- 4
- 主要终点
- Time to initiation
研究概览
简要总结
A Phase 4 operational study to assess the effectiveness, feasibility, acceptability, and cost effectiveness of the GeneXpert MTB/XDR (Xpert XDR; Cepheid) assay for rapid triage-and-treatment of DR-TB-A multi-centre, multi-country prospective cohort study
详细描述
The TriAD study is a multi-center, multi-country Prospective Pragmatic Cohort study assessing the effectiveness, feasibility, acceptability, and cost-effectiveness of implementing the Xpert MTB/XDR (Xpert XDR; Cepheid) assay for rapid triage-and-treatment with short, all- oral drug resistant tuberculosis (DR-TB) treatment. The proposed study aims to screen approximately 4800 GeneXpert MTB/RIF or Ultra MTB-positive (irrespective of rifampicin resistance status) patients from 9 study sites in South Africa, Nigeria and Ethiopia to enrol 880 rifampicin resistant (RR) and 400 isoniazid mono-resistant (HR) patients over a period of 12-18 months. The Xpert XDR assay, a rapid genotypic test, will be implemented as a reflex test to detect resistance to isoniazid, fluoroquinolones and second-line injectable agents to provide rapid genotypic susceptibility testing for DR-TB detection. Patients that test positive for Mycobacterium tuberculosis with rifampicin resistance will be enrolled in Cohort 1 (n=880). Patients that test positive for Mycobacterium tuberculosis that are rifampicin susceptible with isoniazid mono-resistance will be enrolled in Cohort 2 (n=400). Results from the Xpert XDR assay will be used to guide selection of appropriate, evidence-based, all-oral DR-TB treatment regimens of shortest possible duration. The tuberculosis molecular bacterial load assay (TB-MBLA) will be used as an adjunct to provide bacillary load monitoring over the course of treatment to assess real-time treatment response. Operational research will provide information about the feasibility, acceptability and cost-effectiveness to inform policies and guidelines for programmatic implementation of the triage-and-treat model.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ambulant adults ≥ 18 years of age
- •Newly diagnosed PTB patients receiving less than 5 days of treatment since new diagnosis:
- •Cohort 1: < 5 days of DR-TB treatment
- •Cohort 2: < 5 days of INH mono-resistant TB treatment preceding study entry for the current TB episode, or
- •Sputum positive (smear and or culture) TB patients classified as failing first line treatment
- •Any currently available Nucleic Acid Amplification Tests for drug-resistance detection changes/assay positive for M.tb infection with:
- •Cohort 1: at least Rifampicin resistance Cohort 2: Rifampicin susceptible co-occurring with INH, fluoroquinolone, ethionamide or aminoglycoside resistance (detected by Xpert XDR) occurring alone or in combination
- •Capacity to provide informed consent
- •HIV infected and uninfected participants are allowed in the study. Participants already on ART will be allowed in the study provided the ART regimen in use has no contraindications to the proposed TB drug regimen
- •Willing to have samples collected, stored indefinitely, and used for research purposes
- •Able to provide reasonable proof of identity (to satisfaction of study team member) at or prior to enrolment
- •Exclusion criteria:
- •Has a known severe allergy to any of the BPaL component drugs
- •Has DST showing infection with a strain resistant to any of the component drugs
- •Has TB meningitis, other central nervous system TB, or TB osteomyelitis; or
- •Is pregnant or breastfeeding
- •Is unable to take oral medications
- •Persons with any other medical condition, precluding study participation based on investigator judgement
- •Any co-existing condition that in the opinion of the attending clinician renders the participant unsuitable for participation in the study
- •Co-enrolment in other interventional research studies
排除标准
- 未提供
结局指标
主要结局
Time to initiation
时间窗: 4 years
Time to initiation of an appropriate all oral treatment regimen from date of first sputum collected
Proportion of patients with favorable treatment outcomes
时间窗: 4 years
Proportion of patients with favorable treatment outcomes at month 12 from diagnosis
次要结局
- Adverse Drug Reactions(4 years)
- Mortality(4 years)
- Time to culture Conversion(4 years)
- HR TB Prevalence(4 years)
- XDR TB Prevalence(4 years)
- Quality of Xpert XDR testing(4 years)
- Cost effectiveness(4 years)
- Operational Feasibility of patient triaging(4 years)
- Proportion of patients with Bedaquiline and linezolid resistance not eligible for short course treatment(4 years)
- Clinical utility of the Tuberculosis Molecular Bacterial Load Assay (TB-MBLA) compared to routine culture to monitor DR-TB treatment response(4 years)
- Feasibility of Tuberculosis Molecular Bacterial Load Assay (TB-MBLA) will be compared to routine culture in bacteriological follow-up for people on DR-TB treatment(4 years)
- Accuracy of Xpert XDR testing compared to WGS(4 years)
- Resistance profile of sputum samples for identification of drug resistance mutations as per pre-existing probes within the Xpert XDR assay(4 years)
研究者
Dr Kogieleum Naidoo
Associate Professor
Centre for the AIDS Programme of Research in South Africa