Improving tuberculosis diagnosis through innovative testing methods

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

This study is testing new quick tests for tuberculosis to see if they can help health workers find the disease and drug resistance faster and improve care for patients.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 26436 (estimated)
• Ages: 12 Years and up
• Sex: All
• Sponsor: University of California, San Francisco (Academic / other)
• Locations: 16 sites (Tbilisi and 15 other locations)
• Trial ID: NCT04923958 on ClinicalTrials.gov

What this trial studies

The Rapid Research in Diagnostics Development for TB Network (R2D2 TB Network) aims to enhance tuberculosis (TB) diagnosis by evaluating new triage and diagnostic tests in real-world settings. This initiative brings together experts from various fields to assess the effectiveness of novel tests designed to quickly identify TB and drug resistance. The study focuses on developing point-of-care tests that can be used by frontline health workers, thereby addressing the significant diagnostic gap that leaves millions undiagnosed. By comparing these new tests against established standards, the study seeks to improve patient outcomes and reduce TB transmission globally.

Who should consider this trial

Good fit: Ideal candidates for this study are non-hospitalized adults aged 12 years and older with a cough lasting more than two weeks or those with specific risk factors for TB.

Not a fit: Patients who have completed treatment for latent or active TB within the past 12 months may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to faster and more accurate TB diagnoses, ultimately saving lives and reducing the global burden of the disease.

How similar studies have performed: Other studies have shown promise in improving TB diagnostics through innovative approaches, indicating that this research builds on existing knowledge while exploring novel methods.

Eligibility 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.

Where this trial is running

Tbilisi and 15 other locations

• 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)

Study contacts

• Principal investigator: Adithya Cattamanchi, MD — University of California, San Francisco
• Study coordinator: Adithya Cattamanchi, MD

Conditions Tuberculosis; Diagnostics; Global Health