Assessing Diagnostics At Point-of-care for Tuberculosis

Tuberculosis Clinical Trial

— ADAPT  

Official title:

Supporting, Mobilizing and Accelerating Research for Tuberculosis Elimination (SMART4TB)- Technical Area (TA) 1: Diagnostics- Assessing Diagnostics At Point-of-care for Tuberculosis (ADAPT)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05941052
• Other study ID #: 7200AA22RFA00004
• Status: Recruiting
• Phase: N/A
• Start date: August 28, 2023
• Est. completion date: September 30, 2028

Study information

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

Clinical Trial Summary

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 Assessing Diagnostics At Point-of-care for Tuberculosis (ADAPT) study seeks to reduce the burden of TB worldwide by evaluating faster, simpler, and less expensive TB triage and diagnostic tests.

Description:

The Assessing Diagnostics At Point-of-care for Tuberculosis (ADAPT) seeks to identify and rigorously assess promising, design-locked point-of-care (POC) tuberculosis (TB) diagnostic tests (hereafter referred to as "novel tests") in clinical studies conducted in settings of intended use. Rapid diagnosis and effective treatment are critical for improving patient outcomes and reducing TB transmission. However, nearly one-third of people with TB are not diagnosed or reported to public health authorities.The different types of tests required to reduce this "diagnostic gap" have been described in the form of target product profiles (TPPs) defined by the World Health Organization (WHO). The highest priority TPP is that for a point-of-care, non-sputum biomarker-based test to facilitate rapid TB diagnosis using easily accessible samples (i.e., a biomarker-based diagnostic test). The ADAPT study will evaluate the sensitivity, specificity and yield of novel diagnostic tests against a reference standard including sputum Xpert® Mycobacterium tuberculosis/Rifampicin (MTB/RIF) Ultra and sputum mycobacterial culture among adolescents and adults with presumptive TB (based on having TB symptoms, or TB risk factor + positive TB screening test) presenting to outpatient health facilities in high burden countries. In addition, the usability and acceptability of novel TB diagnostic tests will be assessed through direct observations and surveys of routine health workers.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1350
• Est. completion date: September 30, 2028
• Est. primary completion date: September 30, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Novel TB triage and diagnostic tests:

Inclusion Criteria-

The investigators 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. People Living with Human Immunodeficiency Virus (PLHIV) (Risk Factor): C Reactive Protein (CRP) >5 mg/dL OR abnormal chest x-ray (CXR)

2. Self-reported Close Contact (Risk Factor): abnormal CXR History of mining work (Risk Factor): abnormal CXR

Exclusion Criteria-

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

Assessment of the usability of novel TB tests:

Inclusion Criteria-

The investigators 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).

Exclusion Criteria-

The investigators will exclude staff who are:

1) unwilling to provide informed consent

Related Conditions & MeSH terms

• Tuberculosis

Intervention

Diagnostic Test:
• Tongue swab-based molecular assays
The investigators will evaluate semi-automated or automated molecular assays intended for use at near point of care or point of care.

Locations

Country	Name	City	State
Nigeria	Zankli Research Center, Bingham University	Abuja
Philippines	De La Salle Medical and Health Sciences Institute	Dasmariñas
Zambia	Centre for Infectious Disease Research in Zambia	Lusaka

Sponsors (8)

Lead Sponsor	Collaborator
University of California, San Francisco	Bingham University, Centre for Infectious Disease Research in Zambia, De La Salle University Medical Center, Johns Hopkins University, KNCV Tuberculosis Foundation, University Hospital Heidelberg, University of California, Irvine

Countries where clinical trial is conducted

Nigeria,  Philippines,  Zambia, 

References & Publications (7)

Boehme CC, Nabeta P, Hillemann D, Nicol MP, Shenai S, Krapp F, Allen J, Tahirli R, Blakemore R, Rustomjee R, Milovic A, Jones M, O'Brien SM, Persing DH, Ruesch-Gerdes S, Gotuzzo E, Rodrigues C, Alland D, Perkins MD. Rapid molecular detection of tuberculosis and rifampin resistance. N Engl J Med. 2010 Sep 9;363(11):1005-15. doi: 10.1056/NEJMoa0907847. Epub 2010 Sep 1. — View Citation

Cho SN, Brennan PJ. Tuberculosis: diagnostics. Tuberculosis (Edinb). 2007 Aug;87 Suppl 1:S14-7. doi: 10.1016/j.tube.2007.05.001. Epub 2007 Jun 20. — View Citation

Organization WH. High-priority target product profiles for new tuberculosis diagnostics: report of a consensus meeting. Geneva, Switzerland: WHO Press, 2014.

Subbaraman R, Nathavitharana RR, Satyanarayana S, Pai M, Thomas BE, Chadha VK, Rade K, Swaminathan S, Mayer KH. The Tuberculosis Cascade of Care in India's Public Sector: A Systematic Review and Meta-analysis. PLoS Med. 2016 Oct 25;13(10):e1002149. doi: 10.1371/journal.pmed.1002149. eCollection 2016 Oct. — View Citation

Walusimbi S, Bwanga F, De Costa A, Haile M, Joloba M, Hoffner S. Meta-analysis to compare the accuracy of GeneXpert, MODS and the WHO 2007 algorithm for diagnosis of smear-negative pulmonary tuberculosis. BMC Infect Dis. 2013 Oct 30;13:507. doi: 10.1186/1471-2334-13-507. — View Citation

World Health Organization. Global tuberculosis report Geneva, Switzerland: World Health Organization, 2015.

Xpert MTB/RIF Implementation Manual: Technical and Operational 'How-To'; Practical Considerations. Geneva: World Health Organization; 2014. Available from http://www.ncbi.nlm.nih.gov/books/NBK254323/ — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion with positive index test result among participants with tuberculosis (TB)	Sensitivity - Number with positive index test result/(Number with positive or negative index t test result) among participants with TB. TB will be defined based on a microbiological reference standard (sputum mycobacterial culture results)	2 years
Primary	Proportion with negative index test result among participants without tuberculosis (TB)	Specificity - Number with negative index test results/(Number with positive or negative index t test result) among participants without TB. TB will be defined based on a microbiological reference standard (sputum mycobacterial culture results)	2 years