TB Screening Improves Preventive Therapy Uptake

Not Applicable

Active, not recruiting

• Conditions: Latent Tuberculosis; HIV; Tuberculosis; Tuberculosis Prevention
• Interventions: Device: CRP, point-of-care assay

• Registration Number: NCT04557176
• Lead Sponsor: University of California, San Francisco

Brief Summary

HIV-infected people have an increased risk of developing active tuberculosis (TB). To reduce the burden of TB among people living with HIV (PLHIV), the World Health Organization (WHO) recommends systematic TB screening followed by 1) confirmatory TB testing for all those who screen positive and 2) TB preventive therapy (TPT) for all TPT-eligible PLHIV who screen negative.

The objective of the TB Screening Improves Preventive Therapy Uptake (TB SCRIPT) trial is to determine whether TB screening based on C-reactive protein (CRP) levels, measured using a rapid and low-cost point-of-care (POC) assay, improves TPT uptake and clinical outcomes of PLHIV, relative to symptom-based TB screening.

Detailed Description

The overall objective of the TB SCRIPT trial is to evaluate the effectiveness and cost-effectiveness of POC CRP-based TB screening, which is the next step required for successful scale-up of both systematic TB screening and TPT. The study's central hypothesis is that compared to symptom-based TB screening, a TB screening strategy based on CRP levels measured at the point-of-care will improve TPT uptake, thereby reducing TB incidence and its associated mortality among PLHIV.

To test this hypothesis, the investigators will conduct an individual randomized control trial enrolling PLHIV presenting to clinics in Uganda for routine antiretroviral therapy (ART) initiation. Eligible participants will be randomized to either POC CRP-based TB screening (intervention arm) or symptom-based TB screening (control arm). In both arms, screen-positive participants will undergo confirmatory TB testing; participants found to have prevalent TB will be initiated on standard TB treatment. In both arms, screen-negative participants will be assessed for TPT eligibility; TPT-eligible participants will be initiated on standard TPT. All participants will be followed for 2 years.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2020-09-14
• Study First Submitted QC: 2020-09-14
• Study First Posted: 2020-09-21
• Study Start: 2020-11-16
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-27
• Last Update Posted: 2023-11-29
• Primary Completion: 2025-03-15
• Study Completion: 2025-03-15

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 1719

Inclusion Criteria

• Age ≥ 18 years
• Confirmed HIV+ test result
• CD4 T lymphocyte count of ≤ 350 cells/μL
• Capacity to provide written (or witnessed verbal, if illiterate) informed consent

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Exclusion Criteria

• Completed treatment for active pulmonary or extra-pulmonary TB within the past 2 years
• Completed a full course of TPT within the past year
• Actively taking any internationally-approved medication for TB treatment for any reason, within 2 weeks of study entry
• Prior history of combined ART for HIV treatment for any duration (does not include single-dose ART for prevention of vertical transmission of HIV)
• Currently resides 25 km outside their enrollment site, plans to move 25 km outside their enrollment site in the next 2 years, or plans to transfer their HIV care from their current enrollment site

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
POC CRP-based TB screening	CRP, point-of-care assay	Participants randomized to the intervention arm will undergo POC CRP-based TB screening at study entry. Participants with elevated POC CRP levels (≥8 mg/L) will be regarded as screen-positive and will be referred for confirmatory TB testing. Participants with non-elevated POC CRP levels (\<8 mg/L) will be regarded as screen-negative and will be assessed for TPT eligibility.

Primary Outcome Measures

Name	Time	Method
Microbiologically-confirmed incident TB and all-cause mortality	two years	Time to first diagnosis of microbiologically-confirmed incident TB or death from any cause

Secondary Outcome Measures

Name	Time	Method
TPT uptake: number initiated on TPT	two years	Number screen-negatives prescribed TPT + number screen-positives prescribed TPT
TB incidence: incidence rate	two years	Incident rate of microbiologically-confirmed TB
TB incidence: drug resistant TB	two years	Number diagnosed with drug-resistant incident TB
TPT uptake: number screen-negatives prescribed TPT	two years	Number of screen-negatives prescribed TPT
TB incidence: number diagnosed	two years	Number diagnosed with microbiologically-confirmed incident TB
TB incidence: incidence	two years	Incidence of microbiologically-confirmed TB (excluding prevalent TB cases)
TB incidence: Time to microbiologically-confirmed incident TB diagnosis	two years	Days from three months post-enrollment to incident TB diagnosis (or censoring)
TB incidence: drug resistant TB among people receiving TPT	two years	Proportion of participants receiving TPT diagnosed with incident drug resistant TB
Mortality: number of deaths from any cause	two years	Number who died from any cause
Mortality: all-cause death rate	two years	Rate of deaths from any cause
Mortality: number who died from TB	two years	Number who died from confirmed or probable TB
Prevalent TB diagnosis: number microbiologically-confirmed prevalent TB cases missed by screening test	two years	Number screen-negatives diagnosed with prevalent TB
Prevalent TB treatment: time to treatment of microbiologically-confirmed prevalent TB	two years	Days from prevalent TB diagnosis to initiation of TB treatment
Mortality: time to death from any cause	two years	Number of days from enrollment to death from any cause
TPT uptake: number completing TPT	two years	Number initiated on TPT who completed ≥90% of treatment over prescribed TPT period
Prevalent TB diagnosis: number microbiologically-confirmed prevalent TB cases detected by screening test	two years	Number screen-positives diagnosed with prevalent TB
Prevalent TB treatment: Number treated for prevalent TB	two years	Number initiated on TB treatment 3 months or less after study entry
Prevalent TB treatment: number with microbiologically-confirmed prevalent TB completing treatment	two years	Number diagnosed and treated who completed treatment
TPT uptake: time to TPT initiation	two years	Days from baseline TB screening to initiation of TPT
TPT uptake: number screen-positives prescribed TPT	two years	Number screen-positives prescribed TPT
Prevalent TB diagnosis: number diagnosed with microbiologically-confirmed prevalent TB	two years	Number screen-positives diagnosed with prevalent TB + number screen-negatives diagnosed with prevalent TB

Trial Locations

Locations (1)

Kampala Capital City Authority Clinic; 🇺🇬 Kampala, Uganda