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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
SCREENING
Masking
DOUBLE
Enrollment
1,719
CRP is a non-specific marker of inflammation whose levels rise in the setting of interleukin 6 (IL-6)-mediated inflammation, such as active TB. In clinical settings, CRP is used to identify patients with systemic inflammation from infection or non-infectious cases. In settings with high TB prevalence, the investigators hypothesize that CRP can be used to accurately screen individuals for active TB (i.e., distinguish individuals with high likelihood of having active TB from those individuals unlikely to have active TB).
Kampala Capital City Authority Clinic
Kampala, Uganda
Microbiologically-confirmed incident TB and all-cause mortality
Time to first diagnosis of microbiologically-confirmed incident TB or death from any cause
Time frame: two years
TB incidence: number diagnosed
Number diagnosed with microbiologically-confirmed incident TB
Time frame: two years
TB incidence: incidence
Incidence of microbiologically-confirmed TB (excluding prevalent TB cases)
Time frame: two years
TB incidence: Time to microbiologically-confirmed incident TB diagnosis
Days from three months post-enrollment to incident TB diagnosis (or censoring)
Time frame: two years
TB incidence: incidence rate
Incident rate of microbiologically-confirmed TB
Time frame: two years
TB incidence: drug resistant TB
Number diagnosed with drug-resistant incident TB
Time frame: two years
TB incidence: drug resistant TB among people receiving TPT
Proportion of participants receiving TPT diagnosed with incident drug resistant TB
Time frame: two years
Mortality: number of deaths from any cause
Number who died from any cause
Time frame: two years
Mortality: time to death from any cause
Number of days from enrollment to death from any cause
Time frame: two years
Mortality: all-cause death rate
Rate of deaths from any cause
Time frame: two years
Mortality: number who died from TB
Number who died from confirmed or probable TB
Time frame: two years
TPT uptake: number screen-negatives prescribed TPT
Number of screen-negatives prescribed TPT
Time frame: two years
TPT uptake: number screen-positives prescribed TPT
Number screen-positives prescribed TPT
Time frame: two years
TPT uptake: number initiated on TPT
Number screen-negatives prescribed TPT + number screen-positives prescribed TPT
Time frame: two years
TPT uptake: time to TPT initiation
Days from baseline TB screening to initiation of TPT
Time frame: two years
TPT uptake: number completing TPT
Number initiated on TPT who completed ≥90% of treatment over prescribed TPT period
Time frame: two years
Prevalent TB diagnosis: number microbiologically-confirmed prevalent TB cases detected by screening test
Number screen-positives diagnosed with prevalent TB
Time frame: two years
Prevalent TB diagnosis: number microbiologically-confirmed prevalent TB cases missed by screening test
Number screen-negatives diagnosed with prevalent TB
Time frame: two years
Prevalent TB diagnosis: number diagnosed with microbiologically-confirmed prevalent TB
Number screen-positives diagnosed with prevalent TB + number screen-negatives diagnosed with prevalent TB
Time frame: two years
Prevalent TB treatment: Number treated for prevalent TB
Number initiated on TB treatment 3 months or less after study entry
Time frame: two years
Prevalent TB treatment: number with microbiologically-confirmed prevalent TB completing treatment
Number diagnosed and treated who completed treatment
Time frame: two years
Prevalent TB treatment: time to treatment of microbiologically-confirmed prevalent TB
Days from prevalent TB diagnosis to initiation of TB treatment
Time frame: two years
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