TB Screening Improves Preventive Therapy Uptake

HIV Clinical Trial

— TB SCRIPT  

Official title:

TB Screening Improves Preventive Therapy Uptake Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04557176
• Other study ID #: 18-25623
• Secondary ID: 1R61HL146365-01A
• Status: Active, not recruiting
• Phase: N/A
• Start date: November 16, 2020
• Est. completion date: March 15, 2025

Study information

• Verified date: November 2023
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1719
• Est. completion date: March 15, 2025
• Est. primary completion date: March 15, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• HIV
• Latent Tuberculosis
• Tuberculosis
• Tuberculosis Prevention

Intervention

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).

Locations

Country	Name	City	State
Uganda	Kampala Capital City Authority Clinic	Kampala

Sponsors (5)

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

Country where clinical trial is conducted

Uganda, 

References & Publications (52)

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* Note: There are 52 references in all — Click here to view all references

Outcome

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