TuberculosisTB_GAPSNCT05342064
Closing -TB GAPs - for People Living With HIV: TB Guidance for Adaptable Patient-Centered Service
A study testing patient-centered TB preventive therapy and TB preventive therapy adherence support in people with Tuberculosis and HIV Coinfection, run by Baylor College of Medicine at 5 sites in 5 countries.
Trial 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… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Tuberculosis, HIV Coinfection, Tuberculosis Infection
- What is being tested?
- patient-centered TB preventive therapy and TB preventive therapy adherence support
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6,500 participants
- Where
- 5 sitesin 5 countries
- Study dates
- 11 Jul 2023to Sep 2026
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- HIV positive or HIV exposed and presumptively positive while awaiting confirmatory testing in infants
- 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
Who cannot join
- do not provide informed consent or assent as appropriate or are currently being treated for TB
- OBJECTIVE 3:
- do not provide informed consent or assent as appropriate or are currently being treated for TB
Trial locations and contacts
5 sites in 5 countries.
5 sites in 5 countries
About this study
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).
Read more
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.
- Conditions
- Tuberculosis, HIV Coinfection, Tuberculosis Infection
- Being tested
- patient-centered TB preventive therapy, TB preventive therapy adherence support
- Keywords
- TB/HIV co-infection, pediatric tuberculosis, tuberculosis preventive therapy
- Medical subject headings
- Tuberculosis, HIV Infections, Latent Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
patient-centered TB preventive therapyOther
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 preventive therapy adherence supportOther
As part of this study, enhanced adherence support will be provided via bi-directional messaging and/or via clinic phone calls. All participants randomized to enhanced adherence support will receive a weekly text reminder beginning seven days after the initiation. Each message will ask participants if they would like to be contacted to discuss any questions and will prompt participants to ask questions by text if more convenient or preferable. All text-based questions from participants will be answered by a trained nurse with back up from a physician.
| Study group | Role | What they receive |
|---|---|---|
| Standard of care | No intervention | 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 | Experimental | 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. Receives: Other: patient-centered TB preventive therapy; Other: TB preventive therapy adherence support |
What is being measured
The primary outcome is the main question the study is designed to answer.
TB screening
Sensitivity of C-reactive protein for TB screening compared to the sensitivity of the WHO symptom screening using the McNemar test
Measured: 24-32 months
TB diagnosis
Sensitivity of Xpert Host Response Cartridge compared with the sensitivity of Xpert Ultra on sputum or on gastric aspirate using the McNemar test
Measured: 24-32 months
TPT prevention outcomes
Comparing TPT completion rates in participants randomized to bi-directional messaging support vs. standard support
Measured: 48 months
Cost-effectiveness
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
Measured: 32 months
Secondary outcomes (48)
Proportion of participants selecting 3HP and the proportion selecting 6H when offered a choice within a decentralized model
Measured: 48 months
Proportion of participants completing 6H and the proportion completing 3HP among participants randomized to standard support vs. bidirectional messaging
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.
Measured: 48 months
Proportion of participants initiated on TPT in the control phase vs. the intervention phase
Initiation rates will be estimated by the number of participants initiating TPT divided by the number of instances that TPT was offered
Measured: 48 months
Description of the number of participants with different TB treatment and TPT outcomes at the completion of respective therapies
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.
Measured: 48 months
Number of life years saved through novel TPT approaches
Measured: 32 months
Number of active TB cases averted through novel TPT approaches
Measured: 32 months
Measure the association between participant factors and screening and diagnostic positivity rates
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.
Measured: 24-32 months
Laboratory turnaround time
For all screening and diagnostic tests of the study
Measured: 24-32 months
Result reporting rate
For all screening and diagnostic tests of the study
Measured: 24-32 months
Time-to-treatment initiation
For all screening and diagnostic tests of the study
Measured: 24-32 months
Diagnostic performance of mask sampling with differing forms of quiet and forced expiration (i.e., talking, singing) against standard approaches of sampling
Measured: 24-32 months
Compare alternative stool processing techniques and molecular diagnostics/tests of MTB resistance against clinical and microbiologic reference standards
Done using de-identified stool collected and bio-banked during the study.
Measured: 24-32 months
Compare Alere-LAM diagnostic accuracy with that of the SILVAMP-LAM with both spot and early-morning urine samples
Measured: 24-32 months
Analyze different processing approaches for oral swabs prior to testing by Xpert Ultra vs. other microbiological diagnostic and drug susceptibility tests
Measured: 24-32 months
Compare clinician read of chest radiograph with point-of-care ultrasound interpretation to determine agreement and additive yield of each method
this outcome will be studied only in Eswatini and Malawi
Measured: 24-32 months
Prevalence of extrapulmonary TB by means of point of care ultrasound in participants diagnosed with TB
Measured: 24-32 months
Assess ultrasound inter-reader agreement between hands-on operators
Measured: 24-32 months
Assess ultrasound inter-reader agreement between hands-on operators AND remote expert reviewers
Measured: 24-32 months
Compare the proportion of clinician and computer aided detection chest radiograph interpretation with algorithmic approaches against clinical and microbiologic reference standards
Measured: 24-32 months
Sensitivity of point of care CRP versus the WHO symptom screening
CRP will be performed on whole blood using the FDA approved POC iChroma assay. A CRP of > 10 mg/L will be considered positive
Measured: 24-32 months
Specificity of point of care CRP versus the WHO symptom screening
CRP will be performed on whole blood using the FDA approved POC iChroma assay. A CRP of > 10 mg/L will be considered positive
Measured: 24-32 months
Area under the receiver operator curve of point of care CRP versus the WHO symptom screening
CRP will be performed on whole blood using the FDA approved POC iChroma assay. A CRP of > 10 mg/L will be considered positive
Measured: 24-32 months
Sensitivity of chest radiography versus the WHO symptom screening
Chest radiography will be interpreted as normal or abnormal for the purposes of TB screening and will be evaluated using a standardized interpretation form
Measured: 24-32 months
Area under the receiver operator curve of chest radiography versus the WHO symptom screening
Chest radiography will be interpreted as normal or abnormal for the purposes of TB screening and will be evaluated using a standardized interpretation form
Measured: 24-32 months
Specificity of chest radiography versus the WHO symptom screening
Chest radiography will be interpreted as normal or abnormal for the purposes of TB screening and will be evaluated using a standardized interpretation form
Measured: 24-32 months
Sensitivity of SILVAMP-LAM versus the WHO symptom screening
Measured: 24-32 months
Area under the curve of SILVAMP-LAM versus the WHO symptom screening
Measured: 24-32 months
Specificity of SILVAMP-LAM versus the WHO symptom screening
Measured: 24-32 months
Sensitivity of Xpert Ultra performed on an oral/buccal swab versus Xpert Ultra completed on sputum or gastric aspirate
Measured: 24-32 months
Specificity of Xpert Ultra performed on an oral/buccal swab versus Xpert Ultra completed on sputum or gastric aspirate
Measured: 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
Measured: 24-32 months
Sensitivity of Xpert Ultra performed on stool versus Xpert Ultra completed on sputum or gastric aspirate
Measured: 24-32 months
Specificity of Xpert Ultra performed on stool versus Xpert Ultra completed on sputum or gastric aspirate
Measured: 24-32 months
Area under the receiver operator curve of Xpert Ultra performed on stool versus Xpert Ultra completed on sputum or gastric aspirate
Measured: 24-32 months
Sensitivity of LF-LAM versus Xpert Ultra completed on sputum or gastric aspirate
Measured: 24-32 months
Specificity of LF-LAM versus Xpert Ultra completed on sputum or gastric aspirate
Measured: 24-32 months
Area under the receiver operator curve of LF-LAM versus Xpert Ultra completed on sputum or gastric aspirate
Measured: 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
Measured: 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
Measured: 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
Measured: 24-32 months
Sensitivity of point of care ultrasound versus Xpert Ultra completed on sputum or gastric aspirate
Measured: 24-32 months
Specificity of point of care ultrasound versus Xpert Ultra completed on sputum or gastric aspirate
Measured: 24-32 months
Area under the receiver operator curve of point of care ultrasound versus Xpert Ultra completed on sputum or gastric aspirate
Measured: 24-32 months
Sensitivity of Xpert Host Response Cartridge on blood specimen versus Xpert Ultra completed on sputum or gastric aspirate
The blood specimen is collected at the time of positive screening
Measured: 24-32 months
Specificity of Xpert Host Response Cartridge on blood specimen versus Xpert Ultra completed on sputum or gastric aspirate
The blood specimen is collected at the time of positive screening
Measured: 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
The blood specimen is collected at the time of positive screening
Measured: 24-32 months
Sensitivity of chest radiography for TB screening compared to the sensitivity of the WHO symptom screening using the McNemar test
Measured: 24-32 months
Sensitivity of SILVAMP-LAM for TB screening compared to the sensitivity of the WHO symptom screening using the McNemar test
Measured: 24-32 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2022
- Study start11 Jul 2023
- Primary completionSep 2026 (estimated)
- Study completionSep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- More trials run by Baylor College of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- The study will be implemented within a non-randomized stepped-wedge pragmatic intervention study design with nested randomized screening, diagnostic and adherence studies.
- Masking
- None (open label)
- Enrolment
- 6,500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Centers for Disease Control and Prevention, London School of Hygiene and Tropical Medicine, University of Ottawa, University of Stellenbosch
- Responsible party
- Principal investigator, Anna Mandalakas, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05342064
- Sponsor's protocol ID
- H-51421
- Acronym
- TB_GAPS
- Status last verified
- May 2026
- First submitted
- 3 Mar 2022
- Last updated
- 26 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No