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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05342064
Other study ID # H-51421
Secondary ID
Status Recruiting
Phase N/A
First received
Last updated
Start date July 11, 2023
Est. completion date September 2025

Study information

Verified date August 2023
Source Baylor College of Medicine
Contact Anna Mandalakas, MD, PhD
Phone 832-822-6730
Email anna.mandalakas@bcm.edu
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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, 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.


Recruitment information / eligibility

Status Recruiting
Enrollment 6500
Est. completion date September 2025
Est. primary completion date December 2024
Accepts healthy volunteers No
Gender All
Age group N/A and older
Eligibility 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

Study Design


Intervention

Other:
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 preventive therapy adherence support
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.

Locations

Country Name City State
Swaziland Baylor College of Medicine Children's Foundation Mbabane

Sponsors (5)

Lead Sponsor Collaborator
Baylor College of Medicine Centers for Disease Control and Prevention, London School of Hygiene and Tropical Medicine, University of Ottawa, University of Stellenbosch

Country where clinical trial is conducted

Swaziland, 

Outcome

Type Measure Description Time frame Safety issue
Primary TB screening Sensitivity of C-reactive protein for TB screening compared to the sensitivity of the WHO symptom screening using the McNemar test 24-32 months
Primary 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 24-32 months
Primary TPT prevention outcomes Comparing TPT completion rates in participants randomized to bi-directional messaging support vs. standard support 48 months
Primary 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 32 months
Secondary Proportion of participants selecting 3HP and the proportion selecting 6H when offered a choice within a decentralized model 48 months
Secondary 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. 48 months
Secondary 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 48 months
Secondary 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. 48 months
Secondary Number of life years saved through novel TPT approaches 32 months
Secondary Number of active TB cases averted through novel TPT approaches 32 months
Secondary 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. 24-32 months
Secondary Laboratory turnaround time For all screening and diagnostic tests of the study 24-32 months
Secondary Result reporting rate For all screening and diagnostic tests of the study 24-32 months
Secondary Time-to-treatment initiation For all screening and diagnostic tests of the study 24-32 months
Secondary 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
Secondary 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. 24-32 months
Secondary Compare Alere-LAM diagnostic accuracy with that of the SILVAMP-LAM with both spot and early-morning urine samples 24-32 months
Secondary Analyze different processing approaches for oral swabs prior to testing by Xpert Ultra vs. other microbiological diagnostic and drug susceptibility tests 24-32 months
Secondary 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 24-32 months
Secondary Prevalence of extrapulmonary TB by means of point of care ultrasound in participants diagnosed with TB 24-32 months
Secondary Assess ultrasound inter-reader agreement between hands-on operators 24-32 months
Secondary Assess ultrasound inter-reader agreement between hands-on operators AND remote expert reviewers 24-32 months
Secondary Compare the proportion of clinician and computer aided detection chest radiograph interpretation with algorithmic approaches against clinical and microbiologic reference standards 24-32 months
Secondary 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 24-32 months
Secondary 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 24-32 months
Secondary 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 24-32 months
Secondary 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 24-32 months
Secondary 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 24-32 months
Secondary 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 24-32 months
Secondary Sensitivity of SILVAMP-LAM versus the WHO symptom screening 24-32 months
Secondary Area under the curve of SILVAMP-LAM versus the WHO symptom screening 24-32 months
Secondary Specificity of SILVAMP-LAM versus the WHO symptom screening 24-32 months
Secondary Sensitivity of Xpert Ultra performed on an oral/buccal swab versus Xpert Ultra completed on sputum or gastric aspirate 24-32 months
Secondary Specificity of Xpert Ultra performed on an oral/buccal swab versus Xpert Ultra completed on sputum or gastric aspirate 24-32 months
Secondary 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
Secondary Sensitivity of Xpert Ultra performed on stool versus Xpert Ultra completed on sputum or gastric aspirate 24-32 months
Secondary Specificity of Xpert Ultra performed on stool versus Xpert Ultra completed on sputum or gastric aspirate 24-32 months
Secondary Area under the receiver operator curve of Xpert Ultra performed on stool versus Xpert Ultra completed on sputum or gastric aspirate 24-32 months
Secondary Sensitivity of LF-LAM versus Xpert Ultra completed on sputum or gastric aspirate 24-32 months
Secondary Specificity of LF-LAM versus Xpert Ultra completed on sputum or gastric aspirate 24-32 months
Secondary Area under the receiver operator curve of LF-LAM versus Xpert Ultra completed on sputum or gastric aspirate 24-32 months
Secondary 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
Secondary 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
Secondary 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
Secondary Sensitivity of point of care ultrasound versus Xpert Ultra completed on sputum or gastric aspirate 24-32 months
Secondary Specificity of point of care ultrasound versus Xpert Ultra completed on sputum or gastric aspirate 24-32 months
Secondary Area under the receiver operator curve of point of care ultrasound versus Xpert Ultra completed on sputum or gastric aspirate 24-32 months
Secondary 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 24-32 months
Secondary 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 24-32 months
Secondary 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 24-32 months
Secondary Sensitivity of chest radiography for TB screening compared to the sensitivity of the WHO symptom screening using the McNemar test 24-32 months
Secondary Sensitivity of SILVAMP-LAM for TB screening compared to the sensitivity of the WHO symptom screening using the McNemar test 24-32 months
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