Rapid Research in Diagnostics Development for TB Network

NCT ID: NCT04923958

Last Updated: 2025-11-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

26436 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-04-14

Study Completion Date

2031-05-31

Brief Summary

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To reduce the burden of TB worldwide through more accurate, faster, simpler, and less expensive diagnosis of TB Every year, more than 3 million people with TB remain undiagnosed and 1 million die. Better diagnostics are essential to reducing the enormous burden of TB worldwide. The Rapid Research in Diagnostics Development for TB Network (R2D2 TB Network) brings together experts in TB care, technology assessment, diagnostics development, laboratory medicine, epidemiology, health economics and mathematical modeling with highly experienced clinical study sites in 10 countries.

Detailed Description

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The Rapid Research in Diagnostics Development for TB Network (R2D2 TB Network) study seeks to identify and rigorously assess promising early stage tuberculosis (TB) triage, diagnostic and drug resistance tests (hereafter referred to as "novel tests") in clinical studies conducted in settings of intended use. Rapid diagnosis, identification of drug resistance and effective treatment are critical for improving patient outcomes and reducing TB transmission. However, analysis of care cascades and prevalence surveys indicate that 40-60% of patients with TB are not initiated on effective treatment.1,2 The different types of tests required to reduce this "diagnostic gap" have been described in the form of target product profiles (TPPs). The highest- priority TPPs are for: 1) a point-of-care, non-sputum biomarker-based test to facilitate rapid TB diagnosis using easily accessible samples (a biomarker-based diagnostic test) and 2) a simple, low-cost test that can be used by front-line health workers to rule-out TB (a triage test). The R2D2 TB Network study will evaluate the sensitivity and specificity of novel triage and diagnostic tests against a reference standard including sputum Xpert® MTB/RIF (Mycobacterium tuberculosis/Rifampin) Ultra and sputum mycobacterial culture. The sensitivity and specificity of rapid drug susceptibility tests (rDST) will be compared against a reference standard including culture-based phenotypic DST and whole genome sequencing (WGS) of mycobacterial DNA. In addition, the usability of novel tests will be assessed through direct observations and surveys of routine health workers.

Conditions

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Tuberculosis

Keywords

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Tuberculosis Diagnostics Global Health

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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Evaluation of various novel TB triage and diagnostic tests.

For the novel TB triage and diagnostic tests, the investigators will conduct large-scale evaluation of design-locked tests in a cohort of adults with presumed TB, with nested feasibility/pilot studies of early and late prototype tests. The investigators aim to enroll 300-450 participants per year at each of five enrollment sites for evaluation of various novel TB triage and diagnostic tests and 50 health workers to assess test usability.

Group Type EXPERIMENTAL

Novel mycobacterial culture techniques

Intervention Type DIAGNOSTIC_TEST

We will evaluate tests intended to make culture more sensitive, faster, and have less contamination.

Novel sputum smear microscopy techniques

Intervention Type DIAGNOSTIC_TEST

We will evaluate new staining techniques or visualization methods to increase the sensitivity of smear microscopy.

Sputum-based molecular assays

Intervention Type DIAGNOSTIC_TEST

We will evaluate semi-automated or automated molecular assays intended for use at near point of care or point of care.

Tongue swab-based molecular assays

Intervention Type DIAGNOSTIC_TEST

We will evaluate semi-automated or automated molecular assays intended for use at near point of care or point of care.

Urine LAM assays

Intervention Type DIAGNOSTIC_TEST

We will evaluate urine LAM assays incorporating techniques such as analyte concentration, higher sensitivity or specificity antibodies, or enhanced visualization to improve LAM detection.

Blood-based host immune response assays

Intervention Type DIAGNOSTIC_TEST

We will evaluate assays measuring host immune response parameters intended for use at near point of care or point of care.

Breath-based assays

Intervention Type DIAGNOSTIC_TEST

We will evaluate assays assessing volatile organic compounds or exhaled breath condensate for near point of care of point of care detection of TB.

Artificial intelligence-based digital health tools

Intervention Type DIAGNOSTIC_TEST

We will evaluate AI-based algorithms evaluating images (chest x-ray, ultrasound) or sounds (cough sounds, lung sounds) including an Infrasound-to-ultrasound e-stethoscope (Level 42 AI, USA).

Phage-based assays

Intervention Type DIAGNOSTIC_TEST

We will evaluate assays using phages to lyse mycobacterial cells for detection of DNA or antigens.

Evaluation of novel rDST assays

Clinicians at participating sites will be asked to refer adult patients with rifampin-resistance identified by routine molecular testing. The investigators aim to enroll 100-200 patients per year at each of three enrollment sites for evaluation of novel rDST assays.

Group Type EXPERIMENTAL

Cartridge-based molecular assays for detecting drug resistance

Intervention Type DIAGNOSTIC_TEST

We will evaluate semi-automated or automated molecular assays intended for use at near point of care or point of care.

Sequencing-based assays for detecting drug resistance

Intervention Type DIAGNOSTIC_TEST

We will evaluate targeted and whole genome sequencing assays.

Interventions

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Novel mycobacterial culture techniques

We will evaluate tests intended to make culture more sensitive, faster, and have less contamination.

Intervention Type DIAGNOSTIC_TEST

Novel sputum smear microscopy techniques

We will evaluate new staining techniques or visualization methods to increase the sensitivity of smear microscopy.

Intervention Type DIAGNOSTIC_TEST

Sputum-based molecular assays

We will evaluate semi-automated or automated molecular assays intended for use at near point of care or point of care.

Intervention Type DIAGNOSTIC_TEST

Tongue swab-based molecular assays

We will evaluate semi-automated or automated molecular assays intended for use at near point of care or point of care.

Intervention Type DIAGNOSTIC_TEST

Urine LAM assays

We will evaluate urine LAM assays incorporating techniques such as analyte concentration, higher sensitivity or specificity antibodies, or enhanced visualization to improve LAM detection.

Intervention Type DIAGNOSTIC_TEST

Blood-based host immune response assays

We will evaluate assays measuring host immune response parameters intended for use at near point of care or point of care.

Intervention Type DIAGNOSTIC_TEST

Breath-based assays

We will evaluate assays assessing volatile organic compounds or exhaled breath condensate for near point of care of point of care detection of TB.

Intervention Type DIAGNOSTIC_TEST

Artificial intelligence-based digital health tools

We will evaluate AI-based algorithms evaluating images (chest x-ray, ultrasound) or sounds (cough sounds, lung sounds) including an Infrasound-to-ultrasound e-stethoscope (Level 42 AI, USA).

Intervention Type DIAGNOSTIC_TEST

Phage-based assays

We will evaluate assays using phages to lyse mycobacterial cells for detection of DNA or antigens.

Intervention Type DIAGNOSTIC_TEST

Cartridge-based molecular assays for detecting drug resistance

We will evaluate semi-automated or automated molecular assays intended for use at near point of care or point of care.

Intervention Type DIAGNOSTIC_TEST

Sequencing-based assays for detecting drug resistance

We will evaluate targeted and whole genome sequencing assays.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

Novel TB triage and diagnostic tests:

We will include non-hospitalized adults (age ≥ 12 years) with either 1) cough ≥2 weeks' duration, a commonly accepted criterion for identifying people with presumed pulmonary TB (to facilitate standardization across sites and comparison of test performance across sub-groups or 2) risk factors for which TB screening is recommended (HIV infection, self-reported close contact, history of mining work). People with risk factors will be included if they screen positive for TB based on WHO-recommended screening tools as specified below:

Positive TB screening definitions by risk factor:

1. PLHIV (Risk Factor), CRP \>5 mg/dL OR abnormal CXR (Positive TB screening definition)
2. Self-reported Close Contact (Risk Factor), abnormal CXR (Positive TB screening definition)
3. History of mining work (Risk Factor), abnormal CXR (Positive TB screening definition)

We will exclude people who:

1. completed latent or active TB treatment within the past 12 months (to increase TB prevalence and reduce false-positive results, respectively);
2. have taken any medication with anti-mycobacterial activity (including fluoroquinolones) for any reason, within 2 weeks of study entry (to reduce false-negatives);
3. reside \>20km from the study site or are unwilling to return for follow-up visits; or
4. are unwilling to provide informed consent

Novel TB rDST assays:

We will include adults (age ≥12 years) who are positive for TB and RIF resistance according to routine diagnostic testing (based typically on Xpert MTB/RIF, Xpert MTB/RIF Ultra, or Hain MTBDRplus). We will exclude people who:

1. have negative or contaminated results on all baseline (i.e., enrollment) sputum cultures
2. are unable to provide at least two sputum specimens of 3 mL each within one day of enrollment
3. are unable or unwilling to provide informed consent

Assessment of the usability of novel TB tests:

We will include health workers at each clinical site who are 1) aged ≥18 years and 2) involved in routine TB testing (collecting specimens for or performing TB tests). We will exclude staff who are unwilling to provide informed consent.
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Makerere University

OTHER

Sponsor Role collaborator

Johns Hopkins Bloomberg School of Public Health

OTHER

Sponsor Role collaborator

University Hospital Heidelberg

OTHER

Sponsor Role collaborator

Christian Medical College, Vellore, India

OTHER

Sponsor Role collaborator

Vietnam National Lung Hospital

UNKNOWN

Sponsor Role collaborator

De La Salle University Medical Center

OTHER

Sponsor Role collaborator

University of Stellenbosch

OTHER

Sponsor Role collaborator

Harvard Medical School (HMS and HSDM)

OTHER

Sponsor Role collaborator

Stanford University

OTHER

Sponsor Role collaborator

Foundation for Innovative New Diagnostics, Switzerland

OTHER

Sponsor Role collaborator

Socios En Salud Sucursal, Peru

OTHER

Sponsor Role collaborator

Federal University of Mato Grosso

OTHER

Sponsor Role collaborator

Medical Research Council

OTHER_GOV

Sponsor Role collaborator

National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia

OTHER

Sponsor Role collaborator

Centre for Infectious Disease Research in Zambia

OTHER

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role collaborator

Zankli Research Center

UNKNOWN

Sponsor Role collaborator

University of California, Irvine

OTHER

Sponsor Role collaborator

Johns Hopkins University

OTHER

Sponsor Role collaborator

University of California, San Francisco

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Adithya Cattamanchi, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

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National Center for Tuberculosis and Lung Diseases

Tbilisi, , Georgia

Site Status RECRUITING

Chitoor (Christian Medical College satellite campus)

Vellore, , India

Site Status RECRUITING

Christian Medical College CMC Pulmonary Outpatient Department

Vellore, , India

Site Status RECRUITING

Primary care clinics (Shalom/LCC, CHAD)

Vellore, , India

Site Status RECRUITING

Zankli Research Center

Abuja, , Nigeria

Site Status RECRUITING

De La Salle Medical and Health Sciences Institute

Dasmariñas, , Philippines

Site Status RECRUITING

Brooklyn Chest Hospital

Cape Town, , South Africa

Site Status RECRUITING

Khayelitsha District Health Center

Cape Town, , South Africa

Site Status RECRUITING

Kraaifontein Community Health Clinic

Cape Town, , South Africa

Site Status RECRUITING

Scottsdene primary care clinic

Cape Town, , South Africa

Site Status RECRUITING

Wallacedene primary care clinic

Cape Town, , South Africa

Site Status RECRUITING

Kisenyi Health Center

Kampala, , Uganda

Site Status RECRUITING

Mulago Outpatient Department

Kampala, , Uganda

Site Status RECRUITING

Hanoi Lung Hospital, Outpatient departments

Hanoi, , Vietnam

Site Status RECRUITING

National Lung Hospital, Outpatient departments

Hanoi, , Vietnam

Site Status RECRUITING

Centre for Infectious Disease Research in Zambia

Lusaka, , Zambia

Site Status RECRUITING

Countries

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Georgia India Nigeria Philippines South Africa Uganda Vietnam Zambia

Central Contacts

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Adithya Cattamanchi, MD

Role: CONTACT

Phone: +1-415-206-5489

Email: [email protected]

Catherine Cook, MPH

Role: CONTACT

Phone: 603-988-9940

Email: [email protected]

Facility Contacts

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Nestani Tukvadze

Role: primary

DJ Christopher

Role: primary

DJ Christopher

Role: primary

DJ Christopher

Role: primary

John Bimba, MD

Role: primary

Charles Yu

Role: primary

Grant Theron

Role: primary

Grant Theron

Role: primary

Grant Theron

Role: primary

Grant Theron

Role: primary

Grant Theron

Role: primary

William Worodria

Role: primary

William Worodria

Role: primary

Nhung Nguyen

Role: primary

Nhung Nguyen

Role: primary

Monde Muyoyeta, Bsc, MBChB, PhD

Role: primary

References

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Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

U01AI152087

Identifier Type: NIH

Identifier Source: secondary_id

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R01AI190419

Identifier Type: NIH

Identifier Source: secondary_id

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U01AI152087

Identifier Type: NIH

Identifier Source: org_study_id

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