Rapid Research in Diagnostics Development for TB Network (R2D2 TB Network) Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 26,436
- 试验地点
- 30
- 主要终点
- Sensitivity
研究概览
简要总结
To reduce the burden of TB worldwide through more accurate, faster, simpler, and less expensive diagnosis of TB Every year, more than 3 million people with TB remain undiagnosed and 1 million die. Better diagnostics are essential to reducing the enormous burden of TB worldwide. The Rapid Research in Diagnostics Development for TB Network (R2D2 TB Network) brings together experts in TB care, technology assessment, diagnostics development, laboratory medicine, epidemiology, health economics and mathematical modeling with highly experienced clinical study sites in 10 countries.
详细描述
The Rapid Research in Diagnostics Development for TB Network (R2D2 TB Network) study seeks to identify and rigorously assess promising early stage tuberculosis (TB) triage, diagnostic and drug resistance tests (hereafter referred to as "novel tests") in clinical studies conducted in settings of intended use. Rapid diagnosis, identification of drug resistance and effective treatment are critical for improving patient outcomes and reducing TB transmission. However, analysis of care cascades and prevalence surveys indicate that 40-60% of patients with TB are not initiated on effective treatment.1,2 The different types of tests required to reduce this "diagnostic gap" have been described in the form of target product profiles (TPPs). The highest- priority TPPs are for: 1) a point-of-care, non-sputum biomarker-based test to facilitate rapid TB diagnosis using easily accessible samples (a biomarker-based diagnostic test) and 2) a simple, low-cost test that can be used by front-line health workers to rule-out TB (a triage test). The R2D2 TB Network study will evaluate the sensitivity and specificity of novel triage and diagnostic tests against a reference standard including sputum Xpert® MTB/RIF (Mycobacterium tuberculosis/Rifampin) Ultra and sputum mycobacterial culture. The sensitivity and specificity of rapid drug susceptibility tests (rDST) will be compared against a reference standard including culture-based phenotypic DST and whole genome sequencing (WGS) of mycobacterial DNA. In addition, the usability of novel tests will be assessed through direct observations and surveys of routine health workers.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Novel TB triage and diagnostic tests:
- •We will include non-hospitalized adults (age ≥ 12 years) with either 1) cough ≥2 weeks' duration, a commonly accepted criterion for identifying people with presumed pulmonary TB (to facilitate standardization across sites and comparison of test performance across sub-groups or 2) risk factors for which TB screening is recommended (HIV infection, self-reported close contact, history of mining work). People with risk factors will be included if they screen positive for TB based on WHO-recommended screening tools as specified below:
- •Positive TB screening definitions by risk factor:
- •PLHIV (Risk Factor), CRP >5 mg/dL OR abnormal CXR (Positive TB screening definition)
- •Self-reported Close Contact (Risk Factor), abnormal CXR (Positive TB screening definition)
- •History of mining work (Risk Factor), abnormal CXR (Positive TB screening definition)
- •We will exclude people who:
- •completed latent or active TB treatment within the past 12 months (to increase TB prevalence and reduce false-positive results, respectively);
- •have taken any medication with anti-mycobacterial activity (including fluoroquinolones) for any reason, within 2 weeks of study entry (to reduce false-negatives);
- •reside >20km from the study site or are unwilling to return for follow-up visits; or
- •are unwilling to provide informed consent
- •Novel TB rDST assays:
- •We will include adults (age ≥12 years) who are positive for TB and RIF resistance according to routine diagnostic testing (based typically on Xpert MTB/RIF, Xpert MTB/RIF Ultra, or Hain MTBDRplus). We will exclude people who:
- •have negative or contaminated results on all baseline (i.e., enrollment) sputum cultures
- •are unable to provide at least two sputum specimens of 3 mL each within one day of enrollment
- •are unable or unwilling to provide informed consent
- •Assessment of the usability of novel TB tests:
- •We will include health workers at each clinical site who are 1) aged ≥18 years and 2) involved in routine TB testing (collecting specimens for or performing TB tests). We will exclude staff who are unwilling to provide informed consent.
排除标准
- 未提供
研究组 & 干预措施
Evaluation of various novel TB triage and diagnostic tests.
For the novel TB triage and diagnostic tests, the investigators will conduct large-scale evaluation of design-locked tests in a cohort of adults with presumed TB, with nested feasibility/pilot studies of early and late prototype tests. The investigators aim to enroll 300-450 participants per year at each of five enrollment sites for evaluation of various novel TB triage and diagnostic tests and 50 health workers to assess test usability.
干预措施: Novel mycobacterial culture techniques (Diagnostic Test)
Evaluation of various novel TB triage and diagnostic tests.
For the novel TB triage and diagnostic tests, the investigators will conduct large-scale evaluation of design-locked tests in a cohort of adults with presumed TB, with nested feasibility/pilot studies of early and late prototype tests. The investigators aim to enroll 300-450 participants per year at each of five enrollment sites for evaluation of various novel TB triage and diagnostic tests and 50 health workers to assess test usability.
干预措施: Novel sputum smear microscopy techniques (Diagnostic Test)
Evaluation of various novel TB triage and diagnostic tests.
For the novel TB triage and diagnostic tests, the investigators will conduct large-scale evaluation of design-locked tests in a cohort of adults with presumed TB, with nested feasibility/pilot studies of early and late prototype tests. The investigators aim to enroll 300-450 participants per year at each of five enrollment sites for evaluation of various novel TB triage and diagnostic tests and 50 health workers to assess test usability.
干预措施: Sputum-based molecular assays (Diagnostic Test)
Evaluation of various novel TB triage and diagnostic tests.
For the novel TB triage and diagnostic tests, the investigators will conduct large-scale evaluation of design-locked tests in a cohort of adults with presumed TB, with nested feasibility/pilot studies of early and late prototype tests. The investigators aim to enroll 300-450 participants per year at each of five enrollment sites for evaluation of various novel TB triage and diagnostic tests and 50 health workers to assess test usability.
干预措施: Tongue swab-based molecular assays (Diagnostic Test)
Evaluation of various novel TB triage and diagnostic tests.
For the novel TB triage and diagnostic tests, the investigators will conduct large-scale evaluation of design-locked tests in a cohort of adults with presumed TB, with nested feasibility/pilot studies of early and late prototype tests. The investigators aim to enroll 300-450 participants per year at each of five enrollment sites for evaluation of various novel TB triage and diagnostic tests and 50 health workers to assess test usability.
干预措施: Urine LAM assays (Diagnostic Test)
Evaluation of various novel TB triage and diagnostic tests.
For the novel TB triage and diagnostic tests, the investigators will conduct large-scale evaluation of design-locked tests in a cohort of adults with presumed TB, with nested feasibility/pilot studies of early and late prototype tests. The investigators aim to enroll 300-450 participants per year at each of five enrollment sites for evaluation of various novel TB triage and diagnostic tests and 50 health workers to assess test usability.
干预措施: Blood-based host immune response assays (Diagnostic Test)
Evaluation of various novel TB triage and diagnostic tests.
For the novel TB triage and diagnostic tests, the investigators will conduct large-scale evaluation of design-locked tests in a cohort of adults with presumed TB, with nested feasibility/pilot studies of early and late prototype tests. The investigators aim to enroll 300-450 participants per year at each of five enrollment sites for evaluation of various novel TB triage and diagnostic tests and 50 health workers to assess test usability.
干预措施: Breath-based assays (Diagnostic Test)
Evaluation of various novel TB triage and diagnostic tests.
For the novel TB triage and diagnostic tests, the investigators will conduct large-scale evaluation of design-locked tests in a cohort of adults with presumed TB, with nested feasibility/pilot studies of early and late prototype tests. The investigators aim to enroll 300-450 participants per year at each of five enrollment sites for evaluation of various novel TB triage and diagnostic tests and 50 health workers to assess test usability.
干预措施: Artificial intelligence-based digital health tools (Diagnostic Test)
Evaluation of various novel TB triage and diagnostic tests.
For the novel TB triage and diagnostic tests, the investigators will conduct large-scale evaluation of design-locked tests in a cohort of adults with presumed TB, with nested feasibility/pilot studies of early and late prototype tests. The investigators aim to enroll 300-450 participants per year at each of five enrollment sites for evaluation of various novel TB triage and diagnostic tests and 50 health workers to assess test usability.
干预措施: Phage-based assays (Diagnostic Test)
Evaluation of novel rDST assays
Clinicians at participating sites will be asked to refer adult patients with rifampin-resistance identified by routine molecular testing. The investigators aim to enroll 100-200 patients per year at each of three enrollment sites for evaluation of novel rDST assays.
干预措施: Cartridge-based molecular assays for detecting drug resistance (Diagnostic Test)
Evaluation of novel rDST assays
Clinicians at participating sites will be asked to refer adult patients with rifampin-resistance identified by routine molecular testing. The investigators aim to enroll 100-200 patients per year at each of three enrollment sites for evaluation of novel rDST assays.
干预措施: Sequencing-based assays for detecting drug resistance (Diagnostic Test)
结局指标
主要结局
Sensitivity
时间窗: 7 months
Number of positive results for a given index test/(Total positive + negative results for a given index test) among patients with TB using the microbiological reference standard
Specificity
时间窗: 7 months
Number of negative results for a given index test/(Total positive + negative results for a given index test) among patients without TB using the microbiological reference standard
次要结局
未报告次要终点