TB SCRIPT: TB Screening Improves Preventive Therapy Uptake

Sponsor
University of California, San Francisco (Other)
Overall Status
Recruiting
CT.gov ID
NCT04557176
Collaborator
Makerere University (Other), Infectious Diseases Research Collaboration, Uganda (Other), Johns Hopkins University (Other), National Heart, Lung, and Blood Institute (NHLBI) (NIH)
1,720
1
2
51.9
33.1

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Device: CRP, point-of-care assay
N/A

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
1720 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, 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.
Primary Purpose:
Screening
Official Title:
TB Screening Improves Preventive Therapy Uptake Trial
Actual Study Start Date :
Nov 16, 2020
Anticipated Primary Completion Date :
Mar 15, 2025
Anticipated Study Completion Date :
Mar 15, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: POC CRP-based TB screening

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.

Device: CRP, 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).
Other Names:
  • iCHROMA CRP reader
  • Boditech Med Inc.
  • No Intervention: Symptom-based TB screening

    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.

    Outcome Measures

    Primary Outcome Measures

    1. 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

    1. TB incidence: number diagnosed [two years]

      Number diagnosed with microbiologically-confirmed incident TB

    2. TB incidence: incidence [two years]

      Incidence of microbiologically-confirmed TB (excluding prevalent TB cases)

    3. TB incidence: Time to microbiologically-confirmed incident TB diagnosis [two years]

      Days from three months post-enrollment to incident TB diagnosis (or censoring)

    4. TB incidence: incidence rate [two years]

      Incident rate of microbiologically-confirmed TB

    5. TB incidence: drug resistant TB [two years]

      Number diagnosed with drug-resistant incident TB

    6. TB incidence: drug resistant TB among people receiving TPT [two years]

      Proportion of participants receiving TPT diagnosed with incident drug resistant TB

    7. Mortality: number of deaths from any cause [two years]

      Number who died from any cause

    8. Mortality: time to death from any cause [two years]

      Number of days from enrollment to death from any cause

    9. Mortality: all-cause death rate [two years]

      Rate of deaths from any cause

    10. Mortality: number who died from TB [two years]

      Number who died from confirmed or probable TB

    11. TPT uptake: number screen-negatives prescribed TPT [two years]

      Number of screen-negatives prescribed TPT

    12. TPT uptake: number screen-positives prescribed TPT [two years]

      Number screen-positives prescribed TPT

    13. TPT uptake: number initiated on TPT [two years]

      Number screen-negatives prescribed TPT + number screen-positives prescribed TPT

    14. TPT uptake: time to TPT initiation [two years]

      Days from baseline TB screening to initiation of TPT

    15. TPT uptake: number completing TPT [two years]

      Number initiated on TPT who completed ≥90% of treatment over prescribed TPT period

    16. Prevalent TB diagnosis: number microbiologically-confirmed prevalent TB cases detected by screening test [two years]

      Number screen-positives diagnosed with prevalent TB

    17. Prevalent TB diagnosis: number microbiologically-confirmed prevalent TB cases missed by screening test [two years]

      Number screen-negatives diagnosed with prevalent TB

    18. 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

    19. Prevalent TB treatment: Number treated for prevalent TB [two years]

      Number initiated on TB treatment 3 months or less after study entry

    20. Prevalent TB treatment: number with microbiologically-confirmed prevalent TB completing treatment [two years]

      Number diagnosed and treated who completed treatment

    21. Prevalent TB treatment: time to treatment of microbiologically-confirmed prevalent TB [two years]

      Days from prevalent TB diagnosis to initiation of TB treatment

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Kampala Capital City Authority Clinic Kampala Uganda

    Sponsors and Collaborators

    • University of California, San Francisco
    • Makerere University
    • Infectious Diseases Research Collaboration, Uganda
    • Johns Hopkins University
    • National Heart, Lung, and Blood Institute (NHLBI)

    Investigators

    • Principal Investigator: Christina Yoon, MD, University of California, San Francisco

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    University of California, San Francisco
    ClinicalTrials.gov Identifier:
    NCT04557176
    Other Study ID Numbers:
    • 18-25623
    • 1R61HL146365-01A1
    First Posted:
    Sep 21, 2020
    Last Update Posted:
    Apr 28, 2022
    Last Verified:
    Apr 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by University of California, San Francisco
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Apr 28, 2022