HIV, Latent Tuberculosis, Tuberculosis, Tuberculosis Prevention
Conditions
Keywords
Tuberculosis, Latent tuberculosis, Tuberculosis preventive therapy, HIV, C-reactive protein, Symptom screening, Intensified case finding
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.
Interventions
DEVICECRP, point-of-care assay
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).
Sponsors
Makerere University
Infectious Diseases Research Collaboration, Uganda
Johns Hopkins University
National Heart, Lung, and Blood Institute (NHLBI)
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SCREENING
Masking
DOUBLE (Subject, Investigator)
Masking description
Masking will be maintained by administering finger prick tests to all participants, irrespective of trial arm. Intervention arm participants will have CRP levels measured from blood obtained by finger prick. Control arm participants will have beta-human chorionic gonadotropin (beta-hCG) levels measured from blood obtained by finger prick. Only participants, study investigators and routine clinical care providers will be masked. Study staff performing TB screening in accordance with the participant's randomization assignment and activities downstream of TB screening (i.e., confirmatory TB testing, TPT eligibility assessment) will not be masked. The database administrator will have access to the randomized assignments.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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: incidence rate | two years | Incident rate of microbiologically-confirmed TB |
| TB incidence: drug resistant TB | two years | Number diagnosed with drug-resistant incident TB |
| 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: time to death from any cause | two years | Number of days from enrollment to death 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 |
| 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 |
| TPT uptake: number initiated on TPT | two years | Number screen-negatives prescribed TPT + number screen-positives prescribed TPT |
| TPT uptake: time to TPT initiation | two years | Days from baseline TB screening to initiation of TPT |
| 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 diagnosis: number microbiologically-confirmed prevalent TB cases missed by screening test | two years | Number screen-negatives diagnosed with prevalent TB |
| 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 |
| 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 |
| Prevalent TB treatment: time to treatment of microbiologically-confirmed prevalent TB | two years | Days from prevalent TB diagnosis to initiation of TB treatment |
| TPT uptake: number screen-positives prescribed TPT | two years | Number screen-positives prescribed TPT |
Countries
Uganda
Outcome results
None listed