Closing -TB GAPs - for People Living With HIV: TB Guidance for Adaptable Patient-Centered Service
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 6,500
- 试验地点
- 7
- 主要终点
- TB screening
研究概览
简要总结
Tuberculosis (TB) is the world's leading infectious cause of mortality and responsible for 1/3 of deaths in people living with human immunodeficiency virus (PLHIV). Children and adolescents living with HIV (CALHIV) are disproportionately affected due to inadequate preventive services, large case detection gaps, treatment and adherence challenges, and knowledge gaps. This project will generate evidence to inform interventions targeting several of these weaknesses in the TB/HIV cascade of care.
Early detection and treatment of TB improve outcomes in people living with HIV (PLHIV). A key challenge in the detection of HIV-associated TB has been the implementation of screening that identifies the correct population for diagnostic testing. Increasing evidence demonstrates the poor performance of recommended symptom screens and diagnostic approaches. Hence, the investigators aim to define a more accurate TB screening and testing strategy among PLHIV (Objective 1 and Objective 2).
TB preventive treatment (TPT) averts HIV-associated TB. Nevertheless, among PLHIV, TPT initiation and completion rates are sub-optimal and effective delivery strategies are not defined. As such, the investigators aim to identify the most effective TPT delivery strategy through shared decision making and by integrating approaches proven to be effective at improving HIV treatment adherence (Objective 3).
Although evidence demonstrates that isoniazid preventive therapy (IPT) is cost-effective in young children living in TB/HIV high burden settings, the cost-effectiveness of newer short-course TPT has primarily been studied in the context of a TB low-burden, high-income setting. The investigators aim to generate evidence to fill this knowledge gap and inform policy for PLHIV living in TB/HIV high burden settings (Objective 4).
This study is supported by the Centers for Disease Control and Prevention of the U.S. Department of Health and Human Services (HHS) as part of a financial assistance award totaling an anticipated $5,000,000 over five years with 100 percent funded by CDC/HHS.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Other
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •OBJECTIVES 1 and 2:
- •Inclusion Criteria:
- •HIV positive or HIV exposed and presumptively positive while awaiting confirmatory testing in infants
排除标准
- •do not provide informed consent or assent as appropriate or are currently being treated for TB
- •OBJECTIVE 3:
- •Inclusion Criteria:
- •negative TB symptom screen OR for whom TB disease has been ruled out in accordance with WHO Guidelines in adults and according to consensus definitions for child TB
- •Exclusion Criteria:
- •do not provide informed consent or assent as appropriate or are currently being treated for TB
研究组 & 干预措施
Standard of care
No intervention will be administered. Observational data regarding TPT uptake and adherence will be captured on all participants presenting for care
TB screening and evaluation followed by TPT via a decentralized delivery system
The intervention phase includes i) enrolling participants who have had TB disease excluded and allowing participant selection of a preferred TPT regimen, and ii) randomizing participants to one of two participant adherence support modalities.
干预措施: patient-centered TB preventive therapy (Other)
TB screening and evaluation followed by TPT via a decentralized delivery system
The intervention phase includes i) enrolling participants who have had TB disease excluded and allowing participant selection of a preferred TPT regimen, and ii) randomizing participants to one of two participant adherence support modalities.
干预措施: TB preventive therapy adherence support (Other)
结局指标
主要结局
TB screening
时间窗: 24-32 months
Sensitivity of C-reactive protein for TB screening compared to the sensitivity of the WHO symptom screening using the McNemar test
TB diagnosis
时间窗: 24-32 months
Sensitivity of Xpert Host Response Cartridge compared with the sensitivity of Xpert Ultra on sputum or on gastric aspirate using the McNemar test
TPT prevention outcomes
时间窗: 48 months
Comparing TPT completion rates in participants randomized to bi-directional messaging support vs. standard support
Cost-effectiveness
时间窗: 32 months
Estimating the incremental cost-effectiveness of new shortened TPT regimens measured as cost per DALYS averted for each TPT strategy and the enhanced participant support modality compared with current standard of care
次要结局
- Area under the curve of SILVAMP-LAM versus the WHO symptom screening(24-32 months)
- Proportion of participants selecting 3HP and the proportion selecting 6H when offered a choice within a decentralized model(48 months)
- Time-to-treatment initiation(24-32 months)
- Compare Alere-LAM diagnostic accuracy with that of the SILVAMP-LAM with both spot and early-morning urine samples(24-32 months)
- Prevalence of extrapulmonary TB by means of point of care ultrasound in participants diagnosed with TB(24-32 months)
- Sensitivity of SILVAMP-LAM versus the WHO symptom screening(24-32 months)
- Specificity of chest radiography versus the WHO symptom screening(24-32 months)
- Number of life years saved through novel TPT approaches(32 months)
- Diagnostic performance of mask sampling with differing forms of quiet and forced expiration (i.e., talking, singing) against standard approaches of sampling(24-32 months)
- Analyze different processing approaches for oral swabs prior to testing by Xpert Ultra vs. other microbiological diagnostic and drug susceptibility tests(24-32 months)
- Assess ultrasound inter-reader agreement between hands-on operators AND remote expert reviewers(24-32 months)
- Compare the proportion of clinician and computer aided detection chest radiograph interpretation with algorithmic approaches against clinical and microbiologic reference standards(24-32 months)
- Area under the receiver operator curve of Xpert Ultra performed on stool versus Xpert Ultra completed on sputum or gastric aspirate(24-32 months)
- Description of the number of participants with different TB treatment and TPT outcomes at the completion of respective therapies(48 months)
- Assess ultrasound inter-reader agreement between hands-on operators(24-32 months)
- Measure the association between participant factors and screening and diagnostic positivity rates(24-32 months)
- Laboratory turnaround time(24-32 months)
- Compare alternative stool processing techniques and molecular diagnostics/tests of MTB resistance against clinical and microbiologic reference standards(24-32 months)
- Compare clinician read of chest radiograph with point-of-care ultrasound interpretation to determine agreement and additive yield of each method(24-32 months)
- Area under the receiver operator curve of point of care CRP versus the WHO symptom screening(24-32 months)
- Sensitivity of LF-LAM versus Xpert Ultra completed on sputum or gastric aspirate(24-32 months)
- Specificity of LF-LAM versus Xpert Ultra completed on sputum or gastric aspirate(24-32 months)
- Sensitivity of Xpert Ultra performed on a gelatin filter removed from a participant's mask versus Xpert Ultra completed on sputum or gastric aspirate(24-32 months)
- Area under the receiver operator curve of Xpert Ultra performed on a gelatin filter removed from a participant's mask versus Xpert Ultra completed on sputum or gastric aspirate(24-32 months)
- Proportion of participants completing 6H and the proportion completing 3HP among participants randomized to standard support vs. bidirectional messaging(48 months)
- Proportion of participants initiated on TPT in the control phase vs. the intervention phase(48 months)
- Number of active TB cases averted through novel TPT approaches(32 months)
- Result reporting rate(24-32 months)
- Sensitivity of point of care CRP versus the WHO symptom screening(24-32 months)
- Sensitivity of Xpert Ultra performed on stool versus Xpert Ultra completed on sputum or gastric aspirate(24-32 months)
- Specificity of Xpert Ultra performed on stool versus Xpert Ultra completed on sputum or gastric aspirate(24-32 months)
- Area under the receiver operator curve of LF-LAM versus Xpert Ultra completed on sputum or gastric aspirate(24-32 months)
- Sensitivity of point of care ultrasound versus Xpert Ultra completed on sputum or gastric aspirate(24-32 months)
- Area under the receiver operator curve of Xpert Host Response Cartridge on blood specimen versus Xpert Ultra completed on sputum or gastric aspirate(24-32 months)
- Specificity of point of care CRP versus the WHO symptom screening(24-32 months)
- Sensitivity of chest radiography versus the WHO symptom screening(24-32 months)
- Area under the receiver operator curve of chest radiography versus the WHO symptom screening(24-32 months)
- Specificity of SILVAMP-LAM versus the WHO symptom screening(24-32 months)
- Sensitivity of Xpert Ultra performed on an oral/buccal swab versus Xpert Ultra completed on sputum or gastric aspirate(24-32 months)
- Specificity of Xpert Ultra performed on an oral/buccal swab versus Xpert Ultra completed on sputum or gastric aspirate(24-32 months)
- Area under the ROC curve of Xpert Ultra performed on an oral/buccal swab versus Xpert Ultra completed on sputum or gastric aspirate(24-32 months)
- Specificity of Xpert Ultra performed on a gelatin filter removed from a participant's mask versus Xpert Ultra completed on sputum or gastric aspirate(24-32 months)
- Specificity of point of care ultrasound versus Xpert Ultra completed on sputum or gastric aspirate(24-32 months)
- Area under the receiver operator curve of point of care ultrasound versus Xpert Ultra completed on sputum or gastric aspirate(24-32 months)
- Sensitivity of Xpert Host Response Cartridge on blood specimen versus Xpert Ultra completed on sputum or gastric aspirate(24-32 months)
- Specificity of Xpert Host Response Cartridge on blood specimen versus Xpert Ultra completed on sputum or gastric aspirate(24-32 months)
- Sensitivity of chest radiography for TB screening compared to the sensitivity of the WHO symptom screening using the McNemar test(24-32 months)
- Sensitivity of SILVAMP-LAM for TB screening compared to the sensitivity of the WHO symptom screening using the McNemar test(24-32 months)
研究者
Anna Mandalakas
Professor
Baylor College of Medicine