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Active, Not Recruiting

NCT Number: NCT05342064

Closing -TB GAPs - for People Living With HIV: TB Guidance for Adaptable Patient-Centered Service

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Tuberculosis Actinomycetales Infections Bacterial Infections Bacterial Infections and Mycoses Blood-Borne Infections Communicable Diseases Genital Diseases Gram-Positive Bacterial Infections HIV Coinfection HIV Infections Immune System Diseases Immunologic Deficiency Syndromes Infections Latent Infection Latent Tuberculosis Lentivirus Infections Mycobacterium Infections RNA Virus Infections Retroviridae Infections Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Tuberculosis Infection Urogenital Diseases Virus Diseases

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Baylor College of Medicine Children's Foundation, Mbabane, Eswatini

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

OBJECTIVES 1 and 2:

Inclusion criteria

  • HIV positive or HIV exposed and presumptively positive while awaiting confirmatory testing in infants

Exclusion criteria

  • 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

Treatment and study plan

patient-centered TB preventive therapy

Other

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 support

Other

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.

Primary outcomes

  1. TB screening

    Time frame: 24-32 months

    Sensitivity of C-reactive protein for TB screening compared to the sensitivity of the WHO symptom screening using the McNemar test

  2. TB diagnosis

    Time frame: 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

  3. TPT prevention outcomes

    Time frame: 48 months

    Comparing TPT completion rates in participants randomized to bi-directional messaging support vs. standard support

  4. Cost-effectiveness

    Time frame: 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 outcomes

  1. Proportion of participants selecting 3HP and the proportion selecting 6H when offered a choice within a decentralized model

    Time frame: 48 months

  2. Proportion of participants completing 6H and the proportion completing 3HP among participants randomized to standard support vs. bidirectional messaging

    Time frame: 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.

  3. Proportion of participants initiated on TPT in the control phase vs. the intervention phase

    Time frame: 48 months

    Initiation rates will be estimated by the number of participants initiating TPT divided by the number of instances that TPT was offered

  4. Description of the number of participants with different TB treatment and TPT outcomes at the completion of respective therapies

    Time frame: 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.

  5. Number of life years saved through novel TPT approaches

    Time frame: 32 months

  6. Number of active TB cases averted through novel TPT approaches

    Time frame: 32 months

  7. Measure the association between participant factors and screening and diagnostic positivity rates

    Time frame: 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.

  8. Laboratory turnaround time

    Time frame: 24-32 months

    For all screening and diagnostic tests of the study

  9. Result reporting rate

    Time frame: 24-32 months

    For all screening and diagnostic tests of the study

  10. Time-to-treatment initiation

    Time frame: 24-32 months

    For all screening and diagnostic tests of the study

  11. Diagnostic performance of mask sampling with differing forms of quiet and forced expiration (i.e., talking, singing) against standard approaches of sampling

    Time frame: 24-32 months

  12. Compare alternative stool processing techniques and molecular diagnostics/tests of MTB resistance against clinical and microbiologic reference standards

    Time frame: 24-32 months

    Done using de-identified stool collected and bio-banked during the study.

  13. Compare Alere-LAM diagnostic accuracy with that of the SILVAMP-LAM with both spot and early-morning urine samples

    Time frame: 24-32 months

  14. Analyze different processing approaches for oral swabs prior to testing by Xpert Ultra vs. other microbiological diagnostic and drug susceptibility tests

    Time frame: 24-32 months

  15. Compare clinician read of chest radiograph with point-of-care ultrasound interpretation to determine agreement and additive yield of each method

    Time frame: 24-32 months

    this outcome will be studied only in Eswatini and Malawi

  16. Prevalence of extrapulmonary TB by means of point of care ultrasound in participants diagnosed with TB

    Time frame: 24-32 months

  17. Assess ultrasound inter-reader agreement between hands-on operators

    Time frame: 24-32 months

  18. Assess ultrasound inter-reader agreement between hands-on operators AND remote expert reviewers

    Time frame: 24-32 months

  19. Compare the proportion of clinician and computer aided detection chest radiograph interpretation with algorithmic approaches against clinical and microbiologic reference standards

    Time frame: 24-32 months

  20. Sensitivity of point of care CRP versus the WHO symptom screening

    Time frame: 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

  21. Specificity of point of care CRP versus the WHO symptom screening

    Time frame: 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

  22. Area under the receiver operator curve of point of care CRP versus the WHO symptom screening

    Time frame: 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

  23. Sensitivity of chest radiography versus the WHO symptom screening

    Time frame: 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

  24. Area under the receiver operator curve of chest radiography versus the WHO symptom screening

    Time frame: 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

  25. Specificity of chest radiography versus the WHO symptom screening

    Time frame: 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

  26. Sensitivity of SILVAMP-LAM versus the WHO symptom screening

    Time frame: 24-32 months

  27. Area under the curve of SILVAMP-LAM versus the WHO symptom screening

    Time frame: 24-32 months

  28. Specificity of SILVAMP-LAM versus the WHO symptom screening

    Time frame: 24-32 months

  29. Sensitivity of Xpert Ultra performed on an oral/buccal swab versus Xpert Ultra completed on sputum or gastric aspirate

    Time frame: 24-32 months

  30. Specificity of Xpert Ultra performed on an oral/buccal swab versus Xpert Ultra completed on sputum or gastric aspirate

    Time frame: 24-32 months

  31. Area under the ROC curve of Xpert Ultra performed on an oral/buccal swab versus Xpert Ultra completed on sputum or gastric aspirate

    Time frame: 24-32 months

  32. Sensitivity of Xpert Ultra performed on stool versus Xpert Ultra completed on sputum or gastric aspirate

    Time frame: 24-32 months

  33. Specificity of Xpert Ultra performed on stool versus Xpert Ultra completed on sputum or gastric aspirate

    Time frame: 24-32 months

  34. Area under the receiver operator curve of Xpert Ultra performed on stool versus Xpert Ultra completed on sputum or gastric aspirate

    Time frame: 24-32 months

  35. Sensitivity of LF-LAM versus Xpert Ultra completed on sputum or gastric aspirate

    Time frame: 24-32 months

  36. Specificity of LF-LAM versus Xpert Ultra completed on sputum or gastric aspirate

    Time frame: 24-32 months

  37. Area under the receiver operator curve of LF-LAM versus Xpert Ultra completed on sputum or gastric aspirate

    Time frame: 24-32 months

  38. Sensitivity of Xpert Ultra performed on a gelatin filter removed from a participant's mask versus Xpert Ultra completed on sputum or gastric aspirate

    Time frame: 24-32 months

  39. Specificity of Xpert Ultra performed on a gelatin filter removed from a participant's mask versus Xpert Ultra completed on sputum or gastric aspirate

    Time frame: 24-32 months

  40. 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

    Time frame: 24-32 months

  41. Sensitivity of point of care ultrasound versus Xpert Ultra completed on sputum or gastric aspirate

    Time frame: 24-32 months

  42. Specificity of point of care ultrasound versus Xpert Ultra completed on sputum or gastric aspirate

    Time frame: 24-32 months

  43. Area under the receiver operator curve of point of care ultrasound versus Xpert Ultra completed on sputum or gastric aspirate

    Time frame: 24-32 months

  44. Sensitivity of Xpert Host Response Cartridge on blood specimen versus Xpert Ultra completed on sputum or gastric aspirate

    Time frame: 24-32 months

    The blood specimen is collected at the time of positive screening

  45. Specificity of Xpert Host Response Cartridge on blood specimen versus Xpert Ultra completed on sputum or gastric aspirate

    Time frame: 24-32 months

    The blood specimen is collected at the time of positive screening

  46. Area under the receiver operator curve of Xpert Host Response Cartridge on blood specimen versus Xpert Ultra completed on sputum or gastric aspirate

    Time frame: 24-32 months

    The blood specimen is collected at the time of positive screening

  47. Sensitivity of chest radiography for TB screening compared to the sensitivity of the WHO symptom screening using the McNemar test

    Time frame: 24-32 months

  48. Sensitivity of SILVAMP-LAM for TB screening compared to the sensitivity of the WHO symptom screening using the McNemar test

    Time frame: 24-32 months

Sponsors and collaborators

Lead sponsor

Baylor College of Medicine

Other

Collaborators

  • Centers for Disease Control and Prevention
  • London School of Hygiene and Tropical Medicine
  • University of Ottawa
  • University of Stellenbosch

Registry information

Acronym: TB_GAPS

Important dates

Study start
2023
Primary completion
2026
Study completion
2026
First posted
Apr 22, 2022
Registry last updated
May 26, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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