Rapid Research in Diagnostics Development for TB Network (R2D2 TB Network) Study
Trial ID: NCT04923958
Status: RECRUITING
Study type: INTERVENTIONAL
Phase: NA
Start date: 2021-04-14
Completion date: 2031-05-31
Sponsor: University of California, San Francisco
Collaborators: University Hospital Heidelberg; Christian Medical College, Vellore, India; Vietnam National Lung Hospital; De La Salle University Medical Center; University of Stellenbosch; Makerere University; Johns Hopkins Bloomberg School of Public Health; Harvard Medical School (HMS and HSDM); Stanford University; Foundation for Innovative New Diagnostics, Switzerland; Socios En Salud Sucursal, Peru; Federal University of Mato Grosso; Medical Research Council; National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia; Centre for Infectious Disease Research in Zambia; National Institute of Allergy and Infectious Diseases (NIAID); Zankli Research Center; University of California, Irvine; Johns Hopkins University
Conditions: Tuberculosis
Interventions: Novel mycobacterial culture techniques; Novel sputum smear microscopy techniques; Sputum-based molecular assays; Tongue swab-based molecular assays; Urine LAM assays; Blood-based host immune response assays; Breath-based assays; Artificial intelligence-based digital health tools; Phage-based assays; Cartridge-based molecular assays for detecting drug resistance; Sequencing-based assays for detecting drug resistance
Locations: National Center for Tuberculosis and Lung Diseases; Chitoor (Christian Medical College satellite campus); Christian Medical College CMC Pulmonary Outpatient Department; Primary care clinics (Shalom/LCC, CHAD); Zankli Research Center; De La Salle Medical and Health Sciences Institute; Brooklyn Chest Hospital; Khayelitsha District Health Center; Kraaifontein Community Health Clinic; Scottsdene primary care clinic; Wallacedene primary care clinic; Kisenyi Health Center; Mulago Outpatient Department; Hanoi Lung Hospital, Outpatient departments; National Lung Hospital, Outpatient departments; Centre for Infectious Disease Research in Zambia
Countries: Georgia; India; India; India; Nigeria; Philippines; South Africa; South Africa; South Africa; South Africa; South Africa; Uganda; Uganda; Vietnam; Vietnam; Zambia
Enrollment: 26436
Age range: 12 Years - None
Sex: ALL

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.

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.

Outcomes:
Sensitivity; Specificity