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TB Screening Improves Preventive Therapy Uptake (TB SCRIPT)

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ClinicalTrials.gov Identifier: NCT04557176
Recruitment Status : Recruiting
First Posted : September 21, 2020
Last Update Posted : December 16, 2020
Sponsor:
Collaborators:
Makerere University
Infectious Diseases Research Collaboration, Uganda
Johns Hopkins University
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
University of California, San Francisco

Study Description
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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
Tuberculosis Latent Tuberculosis Tuberculosis Prevention HIV Device: CRP, point-of-care assay Not Applicable

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
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Study Type : Interventional  (Clinical Trial)
Estimated 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 : November 16, 2020
Estimated Primary Completion Date : January 2023
Estimated Study Completion Date : January 2023
Arms and Interventions
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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
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Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. TB incidence: number diagnosed [ Time Frame: two years ]
    Number diagnosed with microbiologically-confirmed incident TB

  2. TB incidence: incidence [ Time Frame: two years ]
    Incidence of microbiologically-confirmed TB (excluding prevalent TB cases)

  3. 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)

  4. TB incidence: incidence rate [ Time Frame: two years ]
    Incident rate of microbiologically-confirmed TB

  5. TB incidence: drug resistant TB [ Time Frame: two years ]
    Number diagnosed with drug-resistant incident TB

  6. TB incidence: drug resistant TB among people receiving TPT [ Time Frame: two years ]
    Proportion of participants receiving TPT diagnosed with incident drug resistant TB

  7. Mortality: number of deaths from any cause [ Time Frame: two years ]
    Number who died from any cause

  8. Mortality: time to death from any cause [ Time Frame: two years ]
    Number of days from enrollment to death from any cause

  9. Mortality: all-cause death rate [ Time Frame: two years ]
    Rate of deaths from any cause

  10. Mortality: number who died from TB [ Time Frame: two years ]
    Number who died from confirmed or probable TB

  11. TPT uptake: number screen-negatives prescribed TPT [ Time Frame: two years ]
    Number of screen-negatives prescribed TPT

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

  13. TPT uptake: number initiated on TPT [ Time Frame: two years ]
    Number screen-negatives prescribed TPT + number screen-positives prescribed TPT

  14. TPT uptake: time to TPT initiation [ Time Frame: two years ]
    Days from baseline TB screening to initiation of TPT

  15. TPT uptake: number completing TPT [ Time Frame: 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 [ Time Frame: two years ]
    Number screen-positives diagnosed with prevalent TB

  17. Prevalent TB diagnosis: number microbiologically-confirmed prevalent TB cases missed by screening test [ Time Frame: two years ]
    Number screen-negatives diagnosed with prevalent TB

  18. 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

  19. Prevalent TB treatment: Number treated for prevalent TB [ Time Frame: 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 [ Time Frame: two years ]
    Number diagnosed and treated who completed treatment

  21. 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


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04557176


Contacts
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Contact: Christina Yoon, MD +1 628-206-3514 Christina.Yoon@ucsf.edu

Locations
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Uganda
Kampala Capital City Authority Clinic Recruiting
Kampala, Uganda
Contact: Fred Semitala, MMed         
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
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Principal Investigator: Christina Yoon, MD University of California, San Francisco
More Information
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Publications:
WHO. Global Tuberculosis Report 2017. Geneva, Switzerland. World Health Organization 2017.
TEMPRANO ANRS 12136 Study Group, Danel C, Moh R, Gabillard D, Badje A, Le Carrou J, Ouassa T, Ouattara E, Anzian A, Ntakpé JB, Minga A, Kouame GM, Bouhoussou F, Emieme A, Kouamé A, Inwoley A, Toni TD, Ahiboh H, Kabran M, Rabe C, Sidibé B, Nzunetu G, Konan R, Gnokoro J, Gouesse P, Messou E, Dohoun L, Kamagate S, Yao A, Amon S, Kouame AB, Koua A, Kouamé E, Ndri Y, Ba-Gomis O, Daligou M, Ackoundzé S, Hawerlander D, Ani A, Dembélé F, Koné F, Guéhi C, Kanga C, Koule S, Séri J, Oyebi M, Mbakop N, Makaila O, Babatunde C, Babatounde N, Bleoué G, Tchoutedjem M, Kouadio AC, Sena G, Yededji SY, Assi R, Bakayoko A, Mahassadi A, Attia A, Oussou A, Mobio M, Bamba D, Koman M, Horo A, Deschamps N, Chenal H, Sassan-Morokro M, Konate S, Aka K, Aoussi E, Journot V, Nchot C, Karcher S, Chaix ML, Rouzioux C, Sow PS, Perronne C, Girard PM, Menan H, Bissagnene E, Kadio A, Ettiegne-Traore V, Moh-Semdé C, Kouame A, Massumbuko JM, Chêne G, Dosso M, Domoua SK, N'Dri-Yoman T, Salamon R, Eholié SP, Anglaret X. A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa. N Engl J Med. 2015 Aug 27;373(9):808-22. doi: 10.1056/NEJMoa1507198. Epub 2015 Jul 20.
WHO. Guidelines for intensified tuberculosis case-finding and isoniazid preventive therapy for people living with HIV in resource-constrained settings. Geneva, Switzerland. World Health Organization 2011.
WHO. Latent tuberculosis infection: updated and consolidated guidelines for programmatic management. Geneva, Switzerland. World Health Organization 2018.
WHO. High-priority target product profiles for new tuberculosis diagnostics: report of a consensus meeting. Geneva, Switzerland. World Health Organization 2014.
Uganda Ministry of Health. Report on the Population-based survey of prevalence of tuberculosis disease in Uganda 2014-2015. Kampala: MOH, 2017.
PEPFAR Uganda Program data. (https://www.pepfar.gov/documents/organization/285851.)
Yung-Pin C. Biased coin design with imbalance tolerance. Stochastic Models. 1999 Jan 1;15(5):953-75. doi: 10.1080/15326349908807570
Uganda Ministry of Health. Isoniazid preventive therapy in Uganda: a health worker's guide. Kampala: MOH, 2014.

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Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT04557176    
Other Study ID Numbers: 18-25623
1R61HL146365-01A1 ( U.S. NIH Grant/Contract )
First Posted: September 21, 2020    Key Record Dates
Last Update Posted: December 16, 2020
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
Tuberculosis
Latent tuberculosis
Tuberculosis preventive therapy
HIV
 C-reactive protein
Symptom screening
Intensified case finding
Additional relevant MeSH terms:
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Tuberculosis
Latent Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
 Bacterial Infections
Bacterial Infections and Mycoses
Infections
Latent Infection