Rapid Research in Diagnostics Development for TB Network (R2D2TB Network)

May 4, 2026 updated by: University of California, San Francisco

Rapid Research in Diagnostics Development for TB Network (R2D2 TB Network) Study

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

26436

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 Contact Backup

Study Locations

  • Georgia
  • India
      • Vellore, India
        • Recruiting
        • Chitoor (Christian Medical College satellite campus)
        • Contact:
      • Vellore, India
        • Recruiting
        • Christian Medical College CMC Pulmonary Outpatient Department
        • Contact:
      • Vellore, India
  • Nigeria
  • Philippines
      • Dasmariñas, Philippines
        • Recruiting
        • De La Salle Medical and Health Sciences Institute
        • Contact:
  • South Africa
      • Cape Town, South Africa
      • Cape Town, South Africa
        • Recruiting
        • Khayelitsha District Health Center
        • Contact:
      • Cape Town, South Africa
        • Recruiting
        • Scottsdene primary care clinic
        • Contact:
      • Cape Town, South Africa
        • Recruiting
        • Wallacedene primary care clinic
        • Contact:
      • Cape Town, South Africa
        • Recruiting
        • Kraaifontein Community Health Clinic
        • Contact:
  • Uganda
      • Kampala, Uganda
      • Kampala, Uganda
        • Recruiting
        • Mulago Outpatient Department
        • Contact:
  • Vietnam
      • Hanoi, Vietnam
        • Recruiting
        • Hanoi Lung Hospital, Outpatient departments
        • Contact:
      • Hanoi, Vietnam
        • Recruiting
        • National Lung Hospital, Outpatient departments
        • Contact:
  • Zambia
      • Lusaka, Zambia
        • Recruiting
        • Centre for Infectious Disease Research in Zambia
        • Contact:

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

18 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

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: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Diagnostic test: Novel mycobacterial culture techniques
We will evaluate tests intended to make culture more sensitive, faster, and have less contamination.
Diagnostic test: Novel sputum smear microscopy techniques
We will evaluate new staining techniques or visualization methods to increase the sensitivity of smear microscopy.
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.
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.
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.
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.
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.
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).
Diagnostic test: Phage-based assays
We will evaluate assays using phages to lyse mycobacterial cells for detection of DNA or antigens.
Experimental: 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.
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.
Diagnostic test: Sequencing-based assays for detecting drug resistance
We will evaluate targeted and whole genome sequencing assays.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sensitivity
Time Frame: 7 months
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
Time Frame: 7 months
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

Collaborators and Investigators

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

Sponsor

University of California, San Francisco

Collaborators

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

Investigators

  • Principal Investigator: Adithya Cattamanchi, 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)

April 14, 2021

Primary Completion (Estimated)

May 31, 2031

Study Completion (Estimated)

May 31, 2031

Study Registration Dates

First Submitted

June 7, 2021

First Submitted That Met QC Criteria

June 7, 2021

First Posted (Actual)

June 11, 2021

Study Record Updates

Last Update Posted (Actual)

May 6, 2026

Last Update Submitted That Met QC Criteria

May 4, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • U01AI152087 (U.S. NIH Grant/Contract)
  • R01AI190419 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Study Data/Documents

  1. Individual Participant Data Set

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

Yes

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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