TB Screening Improves Preventive Therapy Uptake (TB SCRIPT)

November 27, 2023 updated by: University of California, San Francisco

TB Screening Improves Preventive Therapy Uptake Trial

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

1719

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Uganda
      • Kampala, Uganda
        • Kampala Capital City Authority Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Screening
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Microbiologically-confirmed incident TB and all-cause mortality
Time Frame: two years
Time to first diagnosis of microbiologically-confirmed incident TB or death from any cause
two years

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Francisco

Collaborators

Johns Hopkins University
National Heart, Lung, and Blood Institute (NHLBI)
Makerere University
Infectious Diseases Research Collaboration, Uganda

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 16, 2020

Primary Completion (Estimated)

March 15, 2025

Study Completion (Estimated)

March 15, 2025

Study Registration Dates

First Submitted

September 14, 2020

First Submitted That Met QC Criteria

September 14, 2020

First Posted (Actual)

September 21, 2020

Study Record Updates

Last Update Posted (Actual)

November 29, 2023

Last Update Submitted That Met QC Criteria

November 27, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 18-25623
  • 1R61HL146365-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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