TB Screening Improves Preventive Therapy Uptake (TB SCRIPT)

University of California San Francisco (UCSF)

Status: Active, not recruiting

Conditions: Tuberculosis; HIV; Tuberculosis Prevention; Latent Tuberculosis

Treatments: Device: CRP, point-of-care assay

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT04557176

18-25623

1R61HL146365-01A1 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 1,719 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

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

Trial design

Primary purpose: Screening

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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1,719 participants in 2 patient groups

POC CRP-based TB screening

Experimental group

Description:

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.

Treatment:

Device: CRP, point-of-care assay

Symptom-based TB screening

No Intervention group

Description:

Participants randomized to the control arm will undergo symptom-based TB screening at study entry. Participants reporting ≥1 TB symptom (current cough, fever, night sweats, weight loss) will be regarded as screen-positive and will be referred for confirmatory TB testing, in accordance with WHO guidelines. Participants with none of the 4 TB symptoms will be regarded as screen-negative and will be assessed for TPT eligibility.