Rapid Research in Diagnostics Development for TB Network

Tuberculosis Clinical Trial

— R2D2TB Network  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04923958
• Other study ID #: U01AI152087
• Secondary ID: U01AI152087
• Status: Recruiting
• Phase: N/A
• Start date: April 14, 2021
• Est. completion date: May 31, 2025

Study information

• Verified date: June 2023
• Source: University of California, San Francisco
• Contact: Adithya Cattamanchi, MD
• Phone: +1-415-206-5489
• Email: adithya.cattamanchi[@]ucsf.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 6050
• Est. completion date: May 31, 2025
• Est. primary completion date: May 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Tuberculosis

Intervention

Diagnostic Test:
• Novel mycobacterial culture techniques
We will evaluate tests intended to make culture more sensitive, faster, and have less contamination.
• Novel sputum smear microscopy techniques
We will evaluate new staining techniques or visualization methods to increase the sensitivity of smear microscopy.
• Sputum-based molecular assays
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 assays
We will evaluate semi-automated or automated molecular assays intended for use at near point of care or point of care.
• Urine LAM assays
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 assays
We will evaluate assays measuring host immune response parameters intended for use at near point of care or point of care.
• Breath-based assays
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 tools
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 assays
We will evaluate assays using phages to lyse mycobacterial cells for detection of DNA or antigens.
• Cartridge-based molecular assays for detecting drug resistance
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 resistance
We will evaluate targeted and whole genome sequencing assays.

Locations

Country	Name	City	State
Georgia	National Center for Tuberculosis and Lung Diseases	Tbilisi
India	Chitoor (Christian Medical College satellite campus)	Vellore
India	Christian Medical College CMC Pulmonary Outpatient Department	Vellore
India	Primary care clinics (Shalom/LCC, CHAD)	Vellore
Philippines	De La Salle Medical and Health Sciences Institute	Dasmariñas
South Africa	Brooklyn Chest Hospital	Cape Town
South Africa	Khayelitsha District Health Center	Cape Town
South Africa	Kraaifontein Community Health Clinic	Cape Town
South Africa	Scottsdene primary care clinic	Cape Town
South Africa	Wallacedene primary care clinic	Cape Town
Uganda	Kisenyi Health Center	Kampala
Uganda	Mulago Outpatient Department	Kampala
Vietnam	Hanoi Lung Hospital, Outpatient departments	Hanoi
Vietnam	National Lung Hospital, Outpatient departments	Hanoi

Sponsors (17)

Lead Sponsor

Collaborator

University of California, San Francisco

Centre for Infectious Disease Research in Zambia, Christian Medical College, Vellore, India, De La Salle University Medical Center, Federal University of Mato Grosso, Foundation for Innovative New Diagnostics, Switzerland, Harvard Medical School (HMS and HSDM), Johns Hopkins Bloomberg School of Public Health, Makerere University, Medical Research Council, National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia, National Institute of Allergy and Infectious Diseases (NIAID), Socios En Salud Sucursal, Peru, Stanford University, University Hospital Heidelberg, University of Stellenbosch, Vietnam National Lung Hospital

Countries where clinical trial is conducted

Georgia,  India,  Philippines,  South Africa,  Uganda,  Vietnam, 

References & Publications (38)

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* Note: There are 38 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	2 years
Primary	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	2 years