Rapid Research in Diagnostics Development for TB Network

NCT04923958 | Recruiting FDA Device

• 2 other identifiers: U01AI152087R01AI190419
• Study Type: interventional
• Target: 26,436
• Locations: 7 countries
• Sites: 11

Brief Summary

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.

Conditions

Tuberculosis

Keywords

Tuberculosis; Diagnostics; Global Health

Outcome Measures

Primary Outcomes (2)

• Sensitivity

  Number of positive results for a given index test/(Total positive + negative results for a given index test) among patients with TB using the microbiological reference standard

  7 months

• Specificity

  Number of negative results for a given index test/(Total positive + negative results for a given index test) among patients without TB using the microbiological reference standard

  7 months

Study Arms (2)

Evaluation of various novel TB triage and diagnostic tests.

EXPERIMENTAL

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.

Diagnostic Test: Novel mycobacterial culture techniques; Diagnostic Test: Novel sputum smear microscopy techniques; Diagnostic Test: Sputum-based molecular assays; Diagnostic Test: Tongue swab-based molecular assays; Diagnostic Test: Urine LAM assays; Diagnostic Test: Blood-based host immune response assays; Diagnostic Test: Breath-based assays; Diagnostic Test: Artificial intelligence-based digital health tools; Diagnostic Test: Phage-based assays

Evaluation of novel rDST assays

EXPERIMENTAL

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.

Diagnostic Test: Cartridge-based molecular assays for detecting drug resistance; Diagnostic Test: Sequencing-based assays for detecting drug resistance

Interventions

Sputum-based molecular assays DIAGNOSTIC_TEST

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

Evaluation of various novel TB triage and diagnostic tests.

Novel mycobacterial culture techniques DIAGNOSTIC_TEST

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

Evaluation of various novel TB triage and diagnostic tests.

Novel sputum smear microscopy techniques DIAGNOSTIC_TEST

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

Evaluation of various novel TB triage and diagnostic tests.

Tongue swab-based molecular assays DIAGNOSTIC_TEST

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

Evaluation of various novel TB triage and diagnostic tests.

Urine LAM assays 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.

Evaluation of various novel TB triage and diagnostic tests.

Blood-based host immune response assays DIAGNOSTIC_TEST

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

Evaluation of various novel TB triage and diagnostic tests.

Breath-based assays 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.

Evaluation of various novel TB triage and diagnostic tests.

Artificial intelligence-based digital health tools 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).

Evaluation of various novel TB triage and diagnostic tests.

Phage-based assays DIAGNOSTIC_TEST

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

Evaluation of various novel TB triage and diagnostic tests.

Cartridge-based molecular assays for detecting drug resistance DIAGNOSTIC_TEST

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

Evaluation of novel rDST assays

Sequencing-based assays for detecting drug resistance DIAGNOSTIC_TEST

We will evaluate targeted and whole genome sequencing assays.

Evaluation of novel rDST assays

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University of California, San Francisco: lead
• University Hospital Heidelberg: collaborator
• Christian Medical College, Vellore, India: collaborator
• Vietnam National Lung Hospital: collaborator
• De La Salle University Medical Center: collaborator
• University of Stellenbosch: collaborator
• Makerere University: collaborator
• Johns Hopkins Bloomberg School of Public Health: collaborator
• Harvard Medical School (HMS and HSDM): collaborator
• Stanford University: collaborator
• Foundation for Innovative New Diagnostics, Switzerland: collaborator
• Socios En Salud Sucursal, Peru: collaborator
• Federal University of Mato Grosso: collaborator
• Medical Research Council: collaborator
• National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia: collaborator
• Centre for Infectious Disease Research in Zambia: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• Zankli Research Center: collaborator
• University of California, Irvine: collaborator
• Johns Hopkins University: collaborator

Study Sites (16)

National Center for Tuberculosis and Lung Diseases

Tbilisi, Georgia

RECRUITING

Chitoor (Christian Medical College satellite campus)

Vellore, India

RECRUITING

Christian Medical College CMC Pulmonary Outpatient Department

Vellore, India

RECRUITING

Primary care clinics (Shalom/LCC, CHAD)

Vellore, India

RECRUITING

Zankli Research Center

Abuja, Nigeria

RECRUITING

De La Salle Medical and Health Sciences Institute

Dasmariñas, Philippines

RECRUITING

Brooklyn Chest Hospital

Cape Town, South Africa

RECRUITING

Khayelitsha District Health Center

Cape Town, South Africa

RECRUITING

Kraaifontein Community Health Clinic

Cape Town, South Africa

RECRUITING

Scottsdene primary care clinic

Cape Town, South Africa

RECRUITING

Wallacedene primary care clinic

Cape Town, South Africa

RECRUITING

Kisenyi Health Center

Kampala, Uganda

RECRUITING

Mulago Outpatient Department

Kampala, Uganda

RECRUITING

Hanoi Lung Hospital, Outpatient departments

Hanoi, Vietnam

RECRUITING

National Lung Hospital, Outpatient departments

Hanoi, Vietnam

RECRUITING

Centre for Infectious Disease Research in Zambia

Lusaka, Zambia

RECRUITING

Related Publications (42)

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MeSH Terms

Conditions

Tuberculosis

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Adithya Cattamanchi, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Adithya Cattamanchi, MD

CONTACT

+1-415-206-5489; adithya.cattamanchi@ucsf.edu

Catherine Cook, MPH

CONTACT

603-988-9940; catherine.cook@ucsf.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2021
• First Posted: June 11, 2021
• Study Start: April 14, 2021
• Primary Completion (Estimated): May 31, 2031
• Study Completion (Estimated): May 31, 2031
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

NG (1); ZA (1); VN (2); PH (1); UG (2); GE (1); IN (3)