Clinical trial NCT05342064: Closing -TB GAPs - for People Living with HIV: TB Guidance for Adaptable Patient-Centered Service
Official title: Closing -TB GAPs - for People Living with HIV: TB Guidance for Adaptable Patient-Centered Service
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Tuberculosis
HIV Coinfection
Tuberculosis Infection
Keywords: TB/HIV co-infection
pediatric tuberculosis
tuberculosis preventive therapy
Lead sponsor: Baylor College of Medicine
Sponsor class: OTHER
Collaborators: name: Centers for Disease Control and Prevention
name: London School of Hygiene and Tropical Medicine
name: University of Ottawa
name: University of Stellenbosch
First posted: 2022-04-22
Enrollment: 6500
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention 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.
Primary purpose: OTHER

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.


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

Primary outcomes:
measure: TB screening
timeFrame: 24-32 months
measure: TB diagnosis
timeFrame: 24-32 months
measure: TPT prevention outcomes
timeFrame: 48 months
measure: Cost-effectiveness
timeFrame: 32 months
Secondary outcomes:
measure: Proportion of participants selecting 3HP and the proportion selecting 6H when offered a choice within a decentralized model
timeFrame: 48 months
measure: Proportion of participants completing 6H and the proportion completing 3HP among participants randomized to standard support vs. bidirectional messaging
timeFrame: 48 months
measure: Proportion of participants initiated on TPT in the control phase vs. the intervention phase
timeFrame: 48 months
measure: Description of the number of participants with different TB treatment and TPT outcomes at the completion of respective therapies
timeFrame: 48 months
measure: Number of life years saved through novel TPT approaches
timeFrame: 32 months
measure: Number of active TB cases averted through novel TPT approaches
timeFrame: 32 months
measure: Measure the association between participant factors and screening and diagnostic positivity rates
timeFrame: 24-32 months
measure: Laboratory turnaround time
timeFrame: 24-32 months
measure: Result reporting rate
timeFrame: 24-32 months
measure: Time-to-treatment initiation
timeFrame: 24-32 months
measure: Diagnostic performance of mask sampling with differing forms of quiet and forced expiration (i.e., talking, singing) against standard approaches of sampling
timeFrame: 24-32 months
measure: Compare alternative stool processing techniques and molecular diagnostics/tests of MTB resistance against clinical and microbiologic reference standards
timeFrame: 24-32 months
measure: Compare Alere-LAM diagnostic accuracy with that of the SILVAMP-LAM with both spot and early-morning urine samples
timeFrame: 24-32 months
measure: Analyze different processing approaches for oral swabs prior to testing by Xpert Ultra vs. other microbiological diagnostic and drug susceptibility tests
timeFrame: 24-32 months
measure: Compare clinician read of chest radiograph with point-of-care ultrasound interpretation to determine agreement and additive yield of each method
timeFrame: 24-32 months
measure: Prevalence of extrapulmonary TB by means of point of care ultrasound in participants diagnosed with TB
timeFrame: 24-32 months
measure: Assess ultrasound inter-reader agreement between hands-on operators
timeFrame: 24-32 months
measure: Assess ultrasound inter-reader agreement between hands-on operators AND remote expert reviewers
timeFrame: 24-32 months
measure: Compare the proportion of clinician and computer aided detection chest radiograph interpretation with algorithmic approaches against clinical and microbiologic reference standards
timeFrame: 24-32 months
measure: Sensitivity of point of care CRP versus the WHO symptom screening
timeFrame: 24-32 months
measure: Specificity of point of care CRP versus the WHO symptom screening
timeFrame: 24-32 months
measure: Area under the receiver operator curve of point of care CRP versus the WHO symptom screening
timeFrame: 24-32 months
measure: Sensitivity of chest radiography versus the WHO symptom screening
timeFrame: 24-32 months
measure: Area under the receiver operator curve of chest radiography versus the WHO symptom screening
timeFrame: 24-32 months
measure: Specificity of chest radiography versus the WHO symptom screening
timeFrame: 24-32 months
measure: Sensitivity of SILVAMP-LAM versus the WHO symptom screening
timeFrame: 24-32 months
measure: Area under the curve of SILVAMP-LAM versus the WHO symptom screening
timeFrame: 24-32 months
measure: Specificity of SILVAMP-LAM versus the WHO symptom screening
timeFrame: 24-32 months
measure: Sensitivity of Xpert Ultra performed on an oral/buccal swab versus Xpert Ultra completed on sputum or gastric aspirate
timeFrame: 24-32 months
measure: Specificity of Xpert Ultra performed on an oral/buccal swab versus Xpert Ultra completed on sputum or gastric aspirate
timeFrame: 24-32 months
measure: Area under the ROC curve of Xpert Ultra performed on an oral/buccal swab versus Xpert Ultra completed on sputum or gastric aspirate
timeFrame: 24-32 months
measure: Sensitivity of Xpert Ultra performed on stool versus Xpert Ultra completed on sputum or gastric aspirate
timeFrame: 24-32 months
measure: Specificity of Xpert Ultra performed on stool versus Xpert Ultra completed on sputum or gastric aspirate
timeFrame: 24-32 months
measure: Area under the receiver operator curve of Xpert Ultra performed on stool versus Xpert Ultra completed on sputum or gastric aspirate
timeFrame: 24-32 months
measure: Sensitivity of LF-LAM versus Xpert Ultra completed on sputum or gastric aspirate
timeFrame: 24-32 months
measure: Specificity of LF-LAM versus Xpert Ultra completed on sputum or gastric aspirate
timeFrame: 24-32 months
measure: Area under the receiver operator curve of LF-LAM versus Xpert Ultra completed on sputum or gastric aspirate
timeFrame: 24-32 months
measure: Sensitivity of Xpert Ultra performed on a gelatin filter removed from a participant's mask versus Xpert Ultra completed on sputum or gastric aspirate
timeFrame: 24-32 months
measure: Specificity of Xpert Ultra performed on a gelatin filter removed from a participant's mask versus Xpert Ultra completed on sputum or gastric aspirate
timeFrame: 24-32 months
measure: 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
timeFrame: 24-32 months
measure: Sensitivity of point of care ultrasound versus Xpert Ultra completed on sputum or gastric aspirate
timeFrame: 24-32 months
measure: Specificity of point of care ultrasound versus Xpert Ultra completed on sputum or gastric aspirate
timeFrame: 24-32 months
measure: Area under the receiver operator curve of point of care ultrasound versus Xpert Ultra completed on sputum or gastric aspirate
timeFrame: 24-32 months
measure: Sensitivity of Xpert Host Response Cartridge on blood specimen versus Xpert Ultra completed on sputum or gastric aspirate
timeFrame: 24-32 months
measure: Specificity of Xpert Host Response Cartridge on blood specimen versus Xpert Ultra completed on sputum or gastric aspirate
timeFrame: 24-32 months
measure: Area under the receiver operator curve of Xpert Host Response Cartridge on blood specimen versus Xpert Ultra completed on sputum or gastric aspirate
timeFrame: 24-32 months
measure: Sensitivity of chest radiography for TB screening compared to the sensitivity of the WHO symptom screening using the McNemar test
timeFrame: 24-32 months
measure: Sensitivity of SILVAMP-LAM for TB screening compared to the sensitivity of the WHO symptom screening using the McNemar test
timeFrame: 24-32 months
Other outcomes:
Locations:
city: Maseru
country: Lesotho
facility: Baylor College of Medicine Children's Foundation
city: Lilongwe
country: Malawi
facility: Baylor College of Medicine Children's Foundation
city: Mbabane
country: Swaziland
facility: Baylor College of Medicine Children's Foundation
city: Mbeya
country: Tanzania
facility: Baylor College of Medicine Children's Foundation
city: Kampala
country: Uganda
facility: Baylor College of Medicine Children's Foundation
Study officials:
References: