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

Primary Purpose

Tuberculosis, HIV Coinfection, Tuberculosis Infection

Status
Recruiting
Phase
Not Applicable
Locations
Swaziland
Study Type
Interventional
Intervention
patient-centered TB preventive therapy
TB preventive therapy adherence support
Sponsored by
Baylor College of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Tuberculosis focused on measuring TB/HIV co-infection, pediatric tuberculosis, tuberculosis preventive therapy

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Baylor College of Medicine Children's FoundationRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Experimental

Arm Label

Standard of care

TB screening and evaluation followed by TPT via a decentralized delivery system

Arm Description

No intervention will be administered. Observational data regarding TPT uptake and adherence will be captured on all participants presenting for care

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.

Outcomes

Primary Outcome Measures

TB screening
Sensitivity of C-reactive protein for TB screening compared to the sensitivity of the WHO symptom screening using the McNemar test
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
TPT prevention outcomes
Comparing TPT completion rates in participants randomized to bi-directional messaging support vs. standard support
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

Secondary Outcome Measures

Proportion of participants selecting 3HP and the proportion selecting 6H when offered a choice within a decentralized model
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.
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
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.
Number of life years saved through novel TPT approaches
Number of active TB cases averted through novel TPT approaches
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.
Laboratory turnaround time
For all screening and diagnostic tests of the study
Result reporting rate
For all screening and diagnostic tests of the study
Time-to-treatment initiation
For all screening and diagnostic tests of the study
Diagnostic performance of mask sampling with differing forms of quiet and forced expiration (i.e., talking, singing) against standard approaches of sampling
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.
Compare Alere-LAM diagnostic accuracy with that of the SILVAMP-LAM with both spot and early-morning urine samples
Analyze different processing approaches for oral swabs prior to testing by Xpert Ultra vs. other microbiological diagnostic and drug susceptibility tests
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
Prevalence of extrapulmonary TB by means of point of care ultrasound in participants diagnosed with TB
Assess ultrasound inter-reader agreement between hands-on operators
Assess ultrasound inter-reader agreement between hands-on operators AND remote expert reviewers
Compare the proportion of clinician and computer aided detection chest radiograph interpretation with algorithmic approaches against clinical and microbiologic reference standards
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
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
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
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
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
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
Sensitivity of SILVAMP-LAM versus the WHO symptom screening
Area under the curve of SILVAMP-LAM versus the WHO symptom screening
Specificity of SILVAMP-LAM versus the WHO symptom screening
Sensitivity of Xpert Ultra performed on an oral/buccal swab versus Xpert Ultra completed on sputum or gastric aspirate
Specificity of Xpert Ultra performed on an oral/buccal swab versus Xpert Ultra completed on sputum or gastric aspirate
Area under the ROC curve of Xpert Ultra performed on an oral/buccal swab versus Xpert Ultra completed on sputum or gastric aspirate
Sensitivity of Xpert Ultra performed on stool versus Xpert Ultra completed on sputum or gastric aspirate
Specificity of Xpert Ultra performed on stool versus Xpert Ultra completed on sputum or gastric aspirate
Area under the receiver operator curve of Xpert Ultra performed on stool versus Xpert Ultra completed on sputum or gastric aspirate
Sensitivity of LF-LAM versus Xpert Ultra completed on sputum or gastric aspirate
Specificity of LF-LAM versus Xpert Ultra completed on sputum or gastric aspirate
Area under the receiver operator curve of LF-LAM versus Xpert Ultra completed on sputum or gastric aspirate
Sensitivity of Xpert Ultra performed on a gelatin filter removed from a participant's mask versus Xpert Ultra completed on sputum or gastric aspirate
Specificity of Xpert Ultra performed on a gelatin filter removed from a participant's mask versus Xpert Ultra completed on sputum or gastric aspirate
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
Sensitivity of point of care ultrasound versus Xpert Ultra completed on sputum or gastric aspirate
Specificity of point of care ultrasound versus Xpert Ultra completed on sputum or gastric aspirate
Area under the receiver operator curve of point of care ultrasound versus Xpert Ultra completed on sputum or gastric aspirate
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
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
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
Sensitivity of chest radiography for TB screening compared to the sensitivity of the WHO symptom screening using the McNemar test
Sensitivity of SILVAMP-LAM for TB screening compared to the sensitivity of the WHO symptom screening using the McNemar test

Full Information

First Posted
March 3, 2022
Last Updated
August 15, 2023
Sponsor
Baylor College of Medicine
Collaborators
Centers for Disease Control and Prevention, London School of Hygiene and Tropical Medicine, University of Ottawa, University of Stellenbosch
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1. Study Identification

Unique Protocol Identification Number
NCT05342064
Brief Title
Closing -TB GAPs - for People Living With HIV: TB Guidance for Adaptable Patient-Centered Service
Acronym
TB_GAPS
Official Title
Closing -TB GAPs - for People Living With HIV: TB Guidance for Adaptable Patient-Centered Service
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 11, 2023 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
September 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Baylor College of Medicine
Collaborators
Centers for Disease Control and Prevention, London School of Hygiene and Tropical Medicine, University of Ottawa, University of Stellenbosch

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberculosis, HIV Coinfection, Tuberculosis Infection
Keywords
TB/HIV co-infection, pediatric tuberculosis, tuberculosis preventive therapy

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Sequential Assignment
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)
Allocation
Non-Randomized
Enrollment
6500 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Standard of care
Arm Type
No Intervention
Arm Description
No intervention will be administered. Observational data regarding TPT uptake and adherence will be captured on all participants presenting for care
Arm Title
TB screening and evaluation followed by TPT via a decentralized delivery system
Arm Type
Experimental
Arm Description
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.
Intervention Type
Other
Intervention Name(s)
patient-centered TB preventive therapy
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
TB preventive therapy adherence support
Intervention Description
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 Outcome Measure Information:
Title
TB screening
Description
Sensitivity of C-reactive protein for TB screening compared to the sensitivity of the WHO symptom screening using the McNemar test
Time Frame
24-32 months
Title
TB diagnosis
Description
Sensitivity of Xpert Host Response Cartridge compared with the sensitivity of Xpert Ultra on sputum or on gastric aspirate using the McNemar test
Time Frame
24-32 months
Title
TPT prevention outcomes
Description
Comparing TPT completion rates in participants randomized to bi-directional messaging support vs. standard support
Time Frame
48 months
Title
Cost-effectiveness
Description
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
Time Frame
32 months
Secondary Outcome Measure Information:
Title
Proportion of participants selecting 3HP and the proportion selecting 6H when offered a choice within a decentralized model
Time Frame
48 months
Title
Proportion of participants completing 6H and the proportion completing 3HP among participants randomized to standard support vs. bidirectional messaging
Description
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.
Time Frame
48 months
Title
Proportion of participants initiated on TPT in the control phase vs. the intervention phase
Description
Initiation rates will be estimated by the number of participants initiating TPT divided by the number of instances that TPT was offered
Time Frame
48 months
Title
Description of the number of participants with different TB treatment and TPT outcomes at the completion of respective therapies
Description
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.
Time Frame
48 months
Title
Number of life years saved through novel TPT approaches
Time Frame
32 months
Title
Number of active TB cases averted through novel TPT approaches
Time Frame
32 months
Title
Measure the association between participant factors and screening and diagnostic positivity rates
Description
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.
Time Frame
24-32 months
Title
Laboratory turnaround time
Description
For all screening and diagnostic tests of the study
Time Frame
24-32 months
Title
Result reporting rate
Description
For all screening and diagnostic tests of the study
Time Frame
24-32 months
Title
Time-to-treatment initiation
Description
For all screening and diagnostic tests of the study
Time Frame
24-32 months
Title
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
Title
Compare alternative stool processing techniques and molecular diagnostics/tests of MTB resistance against clinical and microbiologic reference standards
Description
Done using de-identified stool collected and bio-banked during the study.
Time Frame
24-32 months
Title
Compare Alere-LAM diagnostic accuracy with that of the SILVAMP-LAM with both spot and early-morning urine samples
Time Frame
24-32 months
Title
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
Title
Compare clinician read of chest radiograph with point-of-care ultrasound interpretation to determine agreement and additive yield of each method
Description
this outcome will be studied only in Eswatini and Malawi
Time Frame
24-32 months
Title
Prevalence of extrapulmonary TB by means of point of care ultrasound in participants diagnosed with TB
Time Frame
24-32 months
Title
Assess ultrasound inter-reader agreement between hands-on operators
Time Frame
24-32 months
Title
Assess ultrasound inter-reader agreement between hands-on operators AND remote expert reviewers
Time Frame
24-32 months
Title
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
Title
Sensitivity of point of care CRP versus the WHO symptom screening
Description
CRP will be performed on whole blood using the FDA approved POC iChroma assay. A CRP of > 10 mg/L will be considered positive
Time Frame
24-32 months
Title
Specificity of point of care CRP versus the WHO symptom screening
Description
CRP will be performed on whole blood using the FDA approved POC iChroma assay. A CRP of > 10 mg/L will be considered positive
Time Frame
24-32 months
Title
Area under the receiver operator curve of point of care CRP versus the WHO symptom screening
Description
CRP will be performed on whole blood using the FDA approved POC iChroma assay. A CRP of > 10 mg/L will be considered positive
Time Frame
24-32 months
Title
Sensitivity of chest radiography versus the WHO symptom screening
Description
Chest radiography will be interpreted as normal or abnormal for the purposes of TB screening and will be evaluated using a standardized interpretation form
Time Frame
24-32 months
Title
Area under the receiver operator curve of chest radiography versus the WHO symptom screening
Description
Chest radiography will be interpreted as normal or abnormal for the purposes of TB screening and will be evaluated using a standardized interpretation form
Time Frame
24-32 months
Title
Specificity of chest radiography versus the WHO symptom screening
Description
Chest radiography will be interpreted as normal or abnormal for the purposes of TB screening and will be evaluated using a standardized interpretation form
Time Frame
24-32 months
Title
Sensitivity of SILVAMP-LAM versus the WHO symptom screening
Time Frame
24-32 months
Title
Area under the curve of SILVAMP-LAM versus the WHO symptom screening
Time Frame
24-32 months
Title
Specificity of SILVAMP-LAM versus the WHO symptom screening
Time Frame
24-32 months
Title
Sensitivity of Xpert Ultra performed on an oral/buccal swab versus Xpert Ultra completed on sputum or gastric aspirate
Time Frame
24-32 months
Title
Specificity of Xpert Ultra performed on an oral/buccal swab versus Xpert Ultra completed on sputum or gastric aspirate
Time Frame
24-32 months
Title
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
Title
Sensitivity of Xpert Ultra performed on stool versus Xpert Ultra completed on sputum or gastric aspirate
Time Frame
24-32 months
Title
Specificity of Xpert Ultra performed on stool versus Xpert Ultra completed on sputum or gastric aspirate
Time Frame
24-32 months
Title
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
Title
Sensitivity of LF-LAM versus Xpert Ultra completed on sputum or gastric aspirate
Time Frame
24-32 months
Title
Specificity of LF-LAM versus Xpert Ultra completed on sputum or gastric aspirate
Time Frame
24-32 months
Title
Area under the receiver operator curve of LF-LAM versus Xpert Ultra completed on sputum or gastric aspirate
Time Frame
24-32 months
Title
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
Title
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
Title
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
Title
Sensitivity of point of care ultrasound versus Xpert Ultra completed on sputum or gastric aspirate
Time Frame
24-32 months
Title
Specificity of point of care ultrasound versus Xpert Ultra completed on sputum or gastric aspirate
Time Frame
24-32 months
Title
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
Title
Sensitivity of Xpert Host Response Cartridge on blood specimen versus Xpert Ultra completed on sputum or gastric aspirate
Description
The blood specimen is collected at the time of positive screening
Time Frame
24-32 months
Title
Specificity of Xpert Host Response Cartridge on blood specimen versus Xpert Ultra completed on sputum or gastric aspirate
Description
The blood specimen is collected at the time of positive screening
Time Frame
24-32 months
Title
Area under the receiver operator curve of Xpert Host Response Cartridge on blood specimen versus Xpert Ultra completed on sputum or gastric aspirate
Description
The blood specimen is collected at the time of positive screening
Time Frame
24-32 months
Title
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
Title
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

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Anna Mandalakas, MD, PhD
Phone
832-822-6730
Email
anna.mandalakas@bcm.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Alexander Kay, MD
Email
alexander.kay@bcm.edu
Facility Information:
Facility Name
Baylor College of Medicine Children's Foundation
City
Mbabane
Country
Swaziland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alex Kay
Email
alexander.kay@bcm.edu

12. IPD Sharing Statement

Learn more about this trial

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

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