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TuberculosisR2D2TB NetworkNCT04923958

Rapid Research in Diagnostics Development for TB Network

A study testing Novel mycobacterial culture techniques, Novel sputum smear microscopy techniques and Sputum-based molecular assays in people with Tuberculosis, run by University of California, San Francisco at 16 sites in 8 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 12 years and older
Conditions the study is for
Tuberculosis
What is being tested?
Novel mycobacterial culture techniques, Novel sputum smear microscopy techniques and Sputum-based molecular assays
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26,436 participants
Where
16 sitesin 8 countries
Study dates
14 Apr 2021to 31 May 2031
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

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.

Trial locations and contacts

16 sites in 8 countries. Contact the study team or a site near you to ask about taking part.

Adithya Cattamanchi, MD contact

+1-415-206-5489

adithya.cattamanchi@ucsf.edu

Catherine Cook, MPH contact

603-988-9940

catherine.cook@ucsf.edu

16 sites in 8 countries

South Africa5 sites, 5 recruiting

  • Brooklyn Chest Hospital

    Cape Town

    Grant Theron, gtheron@sun.ac.za

    Recruiting

  • Khayelitsha District Health Center

    Cape Town

    Grant Theron, gtheron@sun.ac.za

    Recruiting

  • Kraaifontein Community Health Clinic

    Cape Town

    Grant Theron, gtheron@sun.ac.za

    Recruiting

  • Scottsdene primary care clinic

    Cape Town

    Grant Theron, gtheron@sun.ac.za

    Recruiting

  • Wallacedene primary care clinic

    Cape Town

    Grant Theron, gtheron@sun.ac.za

    Recruiting

Other trials in South Africa

India3 sites, 3 recruiting

  • Chitoor (Christian Medical College satellite campus)

    Vellore

    DJ Christopher, djchris@cmcvellore.ac.in

    Recruiting

  • Christian Medical College CMC Pulmonary Outpatient Department

    Vellore

    DJ Christopher, djchris@cmcvellore.ac.in

    Recruiting

  • Primary care clinics (Shalom/LCC, CHAD)

    Vellore

    DJ Christopher, djchris@cmcvellore.ac.in

    Recruiting

Other trials in India

Uganda2 sites, 2 recruiting

  • Kisenyi Health Center

    Kampala

    William Worodria, worodria@yahoo.com

    Recruiting

  • Mulago Outpatient Department

    Kampala

    William Worodria, worodria@yahoo.com

    Recruiting

Other trials in Uganda

Vietnam2 sites, 2 recruiting

  • Hanoi Lung Hospital, Outpatient departments

    Hanoi

    Nhung Nguyen, vietnhung@yahoo.com

    Recruiting

  • National Lung Hospital, Outpatient departments

    Hanoi

    Nhung Nguyen, vietnhung@yahoo.com

    Recruiting

Other trials in Vietnam

Georgia1 site, 1 recruiting

  • National Center for Tuberculosis and Lung Diseases

    Tbilisi

    Nestani Tukvadze, Nestan Tukvadze <marikushane@yahoo.com>

    Recruiting

Other trials in Georgia

Nigeria1 site, 1 recruiting

  • Zankli Research Center

    Abuja

    John Bimba, MD, john.bimba@binghamuni.edu.ng

    Recruiting

Other trials in Nigeria

Philippines1 site, 1 recruiting

  • De La Salle Medical and Health Sciences Institute

    Dasmariñas

    Charles Yu, chrlsyu@yahoo.com

    Recruiting

Other trials in Philippines

Zambia1 site, 1 recruiting

  • Centre for Infectious Disease Research in Zambia

    Lusaka

    Monde Muyoyeta, Bsc, MBChB, PhD, monde.muyoyeta@cidrz.org

    Recruiting

Other trials in Zambia

About this study

Official title: 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.

Read the 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.

Conditions
Tuberculosis
Being tested
Novel mycobacterial culture techniques, Novel sputum smear microscopy techniques, Sputum-based molecular assays, Tongue swab-based molecular assays, Urine LAM assays
Keywords
Tuberculosis, Diagnostics, Global Health
Medical subject headings
Tuberculosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Novel mycobacterial culture techniquesDiagnostic test

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

  • Novel sputum smear microscopy techniquesDiagnostic test

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

  • Sputum-based molecular assaysDiagnostic 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 assaysDiagnostic test

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

  • Urine LAM assaysDiagnostic 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 assaysDiagnostic test

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

  • Breath-based assaysDiagnostic 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 toolsDiagnostic 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 assaysDiagnostic test

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

  • Cartridge-based molecular assays for detecting drug resistanceDiagnostic 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 resistanceDiagnostic test

    We will evaluate targeted and whole genome sequencing assays.

Study groups in NCT04923958
Study groupRoleWhat they receive
Evaluation of various novel TB triage and diagnostic tests.ExperimentalFor 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.
Receives: 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 assaysExperimentalClinicians 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.
Receives: Diagnostic Test: Cartridge-based molecular assays for detecting drug resistance; Diagnostic Test: Sequencing-based assays for detecting drug resistance

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 7 months

  2. 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

    Measured: 7 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Jun 2021
  2. Study start14 Apr 2021
  3. Primary completion31 May 2031 (estimated)
  4. Study completion31 May 2031 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Diagnosis
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
26,436 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04923958
Sponsor's protocol ID
U01AI152087
Other IDs
U01AI152087, R01AI190419
Acronym
R2D2TB Network
Status last verified
May 2026
First submitted
7 Jun 2021
Last updated
6 May 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
Yes
Individual data sharing
No

Publications

  • Cho SN, Brennan PJ. Tuberculosis: diagnostics. Tuberculosis (Edinb). 2007 Aug;87 Suppl 1:S14-7. doi: 10.1016/j.tube.2007.05.001. Epub 2007 Jun 20.

    PubMed 17584529

  • World Health Organization. Global tuberculosis report Geneva, Switzerland: World Health Organization, 2015.

  • Boehme CC, Nabeta P, Hillemann D, Nicol MP, Shenai S, Krapp F, Allen J, Tahirli R, Blakemore R, Rustomjee R, Milovic A, Jones M, O'Brien SM, Persing DH, Ruesch-Gerdes S, Gotuzzo E, Rodrigues C, Alland D, Perkins MD. Rapid molecular detection of tuberculosis and rifampin resistance. N Engl J Med. 2010 Sep 9;363(11):1005-15. doi: 10.1056/NEJMoa0907847. Epub 2010 Sep 1.

    PubMed 20825313

  • Walusimbi S, Bwanga F, De Costa A, Haile M, Joloba M, Hoffner S. Meta-analysis to compare the accuracy of GeneXpert, MODS and the WHO 2007 algorithm for diagnosis of smear-negative pulmonary tuberculosis. BMC Infect Dis. 2013 Oct 30;13:507. doi: 10.1186/1471-2334-13-507.

    PubMed 24172543

  • World Health Organization. Rapid Implementation of the Xpert MTB / RIF diagnostic test. Technical and operational 'how-to' practical considerations. Geneva, Switzerland, 2011.

  • Systematic Screening for Active Tuberculosis: Principles and Recommendations. Geneva: World Health Organization; 2013. Available from http://www.ncbi.nlm.nih.gov/books/NBK294083/

    PubMed 25996015

  • World Health Organization. Drug-resistant TB. https://www.who.int/tb/areas-of-work/drug-resistant-tb/en/.

  • Dalton T, Cegielski P, Akksilp S, Asencios L, Campos Caoili J, Cho SN, Erokhin VV, Ershova J, Gler MT, Kazennyy BY, Kim HJ, Kliiman K, Kurbatova E, Kvasnovsky C, Leimane V, van der Walt M, Via LE, Volchenkov GV, Yagui MA, Kang H; Global PETTS Investigators; Akksilp R, Sitti W, Wattanaamornkiet W, Andreevskaya SN, Chernousova LN, Demikhova OV, Larionova EE, Smirnova TG, Vasilieva IA, Vorobyeva AV, Barry CE 3rd, Cai Y, Shamputa IC, Bayona J, Contreras C, Bonilla C, Jave O, Brand J, Lancaster J, Odendaal R, Chen MP, Diem L, Metchock B, Tan K, Taylor A, Wolfgang M, Cho E, Eum SY, Kwak HK, Lee J, Lee J, Min S, Degtyareva I, Nemtsova ES, Khorosheva T, Kyryanova EV, Egos G, Perez MT, Tupasi T, Hwang SH, Kim CK, Kim SY, Lee HJ, Kuksa L, Norvaisha I, Skenders G, Sture I, Kummik T, Kuznetsova T, Somova T, Levina K, Pariona G, Yale G, Suarez C, Valencia E, Viiklepp P. Prevalence of and risk factors for resistance to second-line drugs in people with multidrug-resistant tuberculosis in eight countries: a prospective cohort study. Lancet. 2012 Oct 20;380(9851):1406-17. doi: 10.1016/S0140-6736(12)60734-X. Epub 2012 Aug 30.

    PubMed 22938757

  • Gandhi NR, Moll A, Sturm AW, Pawinski R, Govender T, Lalloo U, Zeller K, Andrews J, Friedland G. Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa. Lancet. 2006 Nov 4;368(9547):1575-80. doi: 10.1016/S0140-6736(06)69573-1.

    PubMed 17084757

  • Masjedi MR, Farnia P, Sorooch S, Pooramiri MV, Mansoori SD, Zarifi AZ, Akbarvelayati A, Hoffner S. Extensively drug-resistant tuberculosis: 2 years of surveillance in Iran. Clin Infect Dis. 2006 Oct 1;43(7):841-7. doi: 10.1086/507542. Epub 2006 Aug 21.

    PubMed 16941364

  • Prasad R, Singh A, Balasubramanian V, Gupta N. Extensively drug-resistant tuberculosis in India: Current evidence on diagnosis & management. Indian J Med Res. 2017 Mar;145(3):271-293. doi: 10.4103/ijmr.IJMR_177_16.

    PubMed 28749390

  • Yoon C, Dowdy DW, Esmail H, MacPherson P, Schumacher SG. Screening for tuberculosis: time to move beyond symptoms. Lancet Respir Med. 2019 Mar;7(3):202-204. doi: 10.1016/S2213-2600(19)30039-6. No abstract available.

    PubMed 30823972

  • Organization WH. High-priority target product profiles for new tuberculosis diagnostics: report of a consensus meeting. Geneva, Switzerland: WHO Press; 2014. p. 98.

  • World Health Organization. High-priority target product profiles for new tuberculosis diagnostics: report of a consensus meeting. Geneva, Switzerland, 2014.

  • UNITAID. TB Diagnostics Market in Select High-Burden Countries: Current Market and Future Opportunities for Novel Diagnostics. Geneva, Switzerland, 2015.

Questions about this trial

What is this clinical trial studying?

A study testing Novel mycobacterial culture techniques, Novel sputum smear microscopy techniques and Sputum-based molecular assays in people with Tuberculosis, run by University of California, San Francisco at 16 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 6 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in South Africa, India, Uganda, Vietnam, Georgia and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Adithya Cattamanchi, MD (+1-415-206-5489, adithya.cattamanchi@ucsf.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Sensitivity (time frame: 7 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04923958, which also lists 42 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2026; AzTrials last refreshed its copy on 27 Oct 2026.

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