Clinical trial NCT04923958: Rapid Research in Diagnostics Development for TB Network
Official title: Rapid Research in Diagnostics Development for TB Network (R2D2 TB Network) Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Tuberculosis
Keywords: Tuberculosis
Diagnostics
Global Health
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: University Hospital Heidelberg
name: Christian Medical College, Vellore, India
name: Vietnam National Lung Hospital
name: De La Salle University Medical Center
name: University of Stellenbosch
name: Makerere University
name: Johns Hopkins Bloomberg School of Public Health
name: Harvard Medical School (HMS and HSDM)
name: Stanford University
name: Foundation for Innovative New Diagnostics, Switzerland
name: Socios En Salud Sucursal, Peru
name: Federal University of Mato Grosso
name: Medical Research Council
name: National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia
name: Centre for Infectious Disease Research in Zambia
name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2021-06-11
Enrollment: 10296
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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.

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.

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.

Primary outcomes:
measure: Sensitivity
timeFrame: 2 years
measure: Specificity
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Tbilisi
country: Georgia
facility: National Center for Tuberculosis and Lung Diseases
city: Vellore
country: India
facility: Chitoor (Christian Medical College satellite campus)
city: Vellore
country: India
facility: Christian Medical College CMC Pulmonary Outpatient Department
city: Vellore
country: India
facility: Primary care clinics (Shalom/LCC, CHAD)
city: Dasmariñas
country: Philippines
facility: De La Salle Medical and Health Sciences Institute
city: Cape Town
country: South Africa
facility: Brooklyn Chest Hospital
city: Cape Town
country: South Africa
facility: Khayelitsha District Health Center
city: Cape Town
country: South Africa
facility: Kraaifontein Community Health Clinic
city: Cape Town
country: South Africa
facility: Scottsdene primary care clinic
city: Cape Town
country: South Africa
facility: Wallacedene primary care clinic
city: Kampala
country: Uganda
facility: Kisenyi Health Center
city: Kampala
country: Uganda
facility: Mulago Outpatient Department
city: Hanoi
country: Vietnam
facility: Hanoi Lung Hospital, Outpatient departments
city: Hanoi
country: Vietnam
facility: National Lung Hospital, Outpatient departments
Study officials:
affiliation: University of California, San Francisco
name: Adithya Cattamanchi, MD
role: PRINCIPAL_INVESTIGATOR
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