Closing -TB GAPs - for People Living With HIV: TB Guidance for Adaptable Patient-Centered Service
- Conditions
- HIV CoinfectionTuberculosis InfectionTuberculosis
- Interventions
- Other: patient-centered TB preventive therapyOther: TB preventive therapy adherence support
- Registration Number
- NCT05342064
- Lead Sponsor
- Baylor College of Medicine
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 6500
- HIV positive or HIV exposed and presumptively positive while awaiting confirmatory testing in infants
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description TB screening and evaluation followed by TPT via a decentralized delivery system patient-centered TB preventive therapy 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. TB screening and evaluation followed by TPT via a decentralized delivery system TB preventive therapy adherence support 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.
- Primary Outcome Measures
Name Time Method TB screening 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 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 48 months Comparing TPT completion rates in participants randomized to bi-directional messaging support vs. standard support
Cost-effectiveness 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
- Secondary Outcome Measures
Name Time Method 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 For all screening and diagnostic tests of the study
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 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 Specificity of chest radiography versus the WHO symptom screening 24-32 months Chest radiography will be interpreted as normal or abnormal for the purposes of TB screening and will be evaluated using a standardized interpretation form
Area under the curve of SILVAMP-LAM versus the WHO symptom screening 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 Result reporting rate 24-32 months For all screening and diagnostic tests of the study
Description of the number of participants with different TB treatment and TPT outcomes at the completion of respective therapies 48 months At individual study end point or at study closure, participants will be classified as i) retained in care, ii) died, iii) lost to follow-up, or iv) transferred out.
Assess ultrasound inter-reader agreement between hands-on operators 24-32 months Sensitivity of point of care CRP versus the WHO symptom screening 24-32 months CRP will be performed on whole blood using the FDA approved POC iChroma assay. A CRP of \> 10 mg/L will be considered positive
Measure the association between participant factors and screening and diagnostic positivity rates 24-32 months Participant factors are inclusive but not limited to TB infection status, immunologic, virologic, demographic, socioeconomic and clinical factors. The screening and diagnosis approaches are: point of care C-reactive protein, chest radiography, Fuji-LAM, Xpert Ultra performed on oral swabs and stool specimens and ultrasound.
Laboratory turnaround time 24-32 months For all screening and diagnostic tests of the study
Compare alternative stool processing techniques and molecular diagnostics/tests of MTB resistance against clinical and microbiologic reference standards 24-32 months Done using de-identified stool collected and bio-banked during the study.
Compare clinician read of chest radiograph with point-of-care ultrasound interpretation to determine agreement and additive yield of each method 24-32 months this outcome will be studied only in Eswatini and Malawi
Area under the receiver operator curve of point of care CRP versus the WHO symptom screening 24-32 months CRP will be performed on whole blood using the FDA approved POC iChroma assay. A CRP of \> 10 mg/L will be considered positive
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 Treatment completion will be defined as receipt of at least 80% of doses during a pre-specified period of time and consistent with WHO definitions.
Proportion of participants initiated on TPT in the control phase vs. the intervention phase 48 months Initiation rates will be estimated by the number of participants initiating TPT divided by the number of instances that TPT was offered
Number of active TB cases averted through novel TPT approaches 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 The blood specimen is collected at the time of positive screening
Specificity of SILVAMP-LAM versus the WHO symptom screening 24-32 months Specificity of point of care CRP versus the WHO symptom screening 24-32 months CRP will be performed on whole blood using the FDA approved POC iChroma assay. A CRP of \> 10 mg/L will be considered positive
Sensitivity of chest radiography versus the WHO symptom screening 24-32 months Chest radiography will be interpreted as normal or abnormal for the purposes of TB screening and will be evaluated using a standardized interpretation form
Area under the receiver operator curve of chest radiography versus the WHO symptom screening 24-32 months Chest radiography will be interpreted as normal or abnormal for the purposes of TB screening and will be evaluated using a standardized interpretation form
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 The blood specimen is collected at the time of positive screening
Specificity of Xpert Host Response Cartridge on blood specimen versus Xpert Ultra completed on sputum or gastric aspirate 24-32 months The blood specimen is collected at the time of positive screening
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
Trial Locations
- Locations (1)
Baylor College of Medicine Children's Foundation
🇺🇬Kampala, Uganda