Rapid Research in Diagnostics Development for TB Network

Not Applicable

Recruiting

• Conditions: Tuberculosis
• Interventions: Diagnostic Test: Novel mycobacterial culture techniques; Diagnostic Test: Cartridge-based molecular assays for detecting drug resistance; Diagnostic Test: Novel sputum smear microscopy techniques; Diagnostic Test: Sequencing-based assays for detecting drug resistance; 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

• Registration Number: NCT04923958
• Lead Sponsor: University of California, San Francisco

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.

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations

Study Timeline

• Study Start: 2021-04-14
• Study First Submitted: 2021-06-07
• Study First Submitted QC: 2021-06-07
• Study First Posted: 2021-06-11
• Status Verified: 2023-06
• Last Update Submitted: 2023-06-27
• Last Update Posted: 2023-06-29
• Primary Completion: 2025-05-31
• Study Completion: 2025-05-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 6050

Inclusion Criteria

Not provided

Read More

Exclusion Criteria

Not provided

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Evaluation of various novel TB triage and diagnostic tests.	Tongue swab-based molecular assays	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.
Evaluation of various novel TB triage and diagnostic tests.	Urine LAM assays	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.
Evaluation of various novel TB triage and diagnostic tests.	Blood-based host immune response assays	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.
Evaluation of various novel TB triage and diagnostic tests.	Novel mycobacterial culture techniques	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.
Evaluation of various novel TB triage and diagnostic tests.	Sputum-based molecular assays	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.
Evaluation of various novel TB triage and diagnostic tests.	Breath-based assays	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.
Evaluation of various novel TB triage and diagnostic tests.	Artificial intelligence-based digital health tools	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.
Evaluation of novel rDST assays	Cartridge-based molecular assays for detecting drug resistance	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.
Evaluation of various novel TB triage and diagnostic tests.	Novel sputum smear microscopy techniques	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.
Evaluation of novel rDST assays	Sequencing-based assays for detecting drug resistance	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.
Evaluation of various novel TB triage and diagnostic tests.	Phage-based assays	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.

Primary Outcome Measures

Name	Time	Method
Sensitivity	2 years	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
Specificity	2 years	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

Trial Locations

Locations (14)

Chitoor (Christian Medical College satellite campus); 🇮🇳 Vellore, India

Kisenyi Health Center; 🇺🇬 Kampala, Uganda

Mulago Outpatient Department; 🇺🇬 Kampala, Uganda

National Center for Tuberculosis and Lung Diseases; 🇬🇪 Tbilisi, Georgia

Primary care clinics (Shalom/LCC, CHAD); 🇮🇳 Vellore, India

Christian Medical College CMC Pulmonary Outpatient Department; 🇮🇳 Vellore, India

De La Salle Medical and Health Sciences Institute; 🇵🇭 Dasmariñas, Philippines

Brooklyn Chest Hospital; 🇿🇦 Cape Town, South Africa

Khayelitsha District Health Center; 🇿🇦 Cape Town, South Africa

Scottsdene primary care clinic; 🇿🇦 Cape Town, South Africa

Kraaifontein Community Health Clinic; 🇿🇦 Cape Town, South Africa

Wallacedene primary care clinic; 🇿🇦 Cape Town, South Africa

National Lung Hospital, Outpatient departments; 🇻🇳 Hanoi, Vietnam

Hanoi Lung Hospital, Outpatient departments; 🇻🇳 Hanoi, Vietnam