Evaluation of Host Biomarker-based Point-of-care Tests for Targeted Screening for Active TB
- Conditions
- Pulmonary Tuberculosis
- Interventions
- Diagnostic Test: Trans-Dot point-of-care test
- Registration Number
- NCT03350048
- Lead Sponsor
- Prof Gerhard Walzl
- Brief Summary
Title: Evaluation of host biomarker-based point-of-care tests for targeted screening for active TB (Screen TB)
Introduction: Tuberculosis (TB) places severe pressure on health care services of the developing world. Despite the introduction of the highly sensitive and specific GeneXpert MTB/RIF (GeneXpert) test \[1\] with a potential turn-around time of two hours, many people in high TB prevalence areas still do not have access to efficient TB diagnostic services due to logistical constraints in these settings. A cost effective, rapid, point-of-care screening test with high sensitivity would identify people with a high likelihood for active TB and would prioritize them for testing with more expensive, technically or logistically demanding assays including GeneXpert or liquid culture, facilitating cost-effective diagnostic work-up in resource-limited settings. A serum cytokine signature for active TB disease, discovered in the AE-TBC project, with a sensitivity of 89% (CI 78 - 95%) and specificity of 76% (CI 68 - 83%), will be optimised and utilized in a point-of-care format (TransDot) to rapidly test for TB disease in symptomatic people.
Hypothesis: The TransDot test will achieve a sensitivity of \> 90% for TB disease, in a training set of people suspected of having TB disease, and be validated (achieve similarly high sensitivity) subsequently in a prospective test set of people suspected of having TB disease, when compared to a composite gold standard of sputum culture, smear, GeneXpert, chest X-ray, TB symptoms and TB treatment response.
Objectives: The overall objective of the study is to incorporate a six-marker serum signature into a multiplex UCP-LFA format, referred to as TransDot, for finger-prick blood testing. The end point of the study is the accuracy (sensitivity and specificity) of the UCP-LFA TransDot test on finger-prick blood for active TB and will be prospectively compared against gold standard composite diagnostic criteria (GeneXpert, MGIT culture, TB sputum smear, CXR, TB symptom screen and response to TB treatment).
Primary: The primary outcome of interest will be accuracy, sensitivity and specificity of the TransDot finger-prick test when compared with the composite gold standard tests.
- Detailed Description
Protocol Summary Title: Evaluation of host biomarker-based point-of-care tests for targeted screening for active TB (Screen TB)
Population: A total of 800 people presenting at primary health care clinics with presumed active pulmonary tuberculosis, aged 18 to 70 years, male or female gender, will be recruited. They should be willing to give informed, written consent, including consent for HIV testing. They should have symptoms that could be compatible with active TB (cough \> two weeks, plus at least one of the following: fever, weight loss, haemoptysis and night sweats). Participants should not have been on TB treatment for the past 90 days and should not have received immune suppressive therapy, be known with alcohol of drug abuse, have a haemoglobin level \<9g/dl or be pregnant or breastfeeding. HIV co-infection is not an exclusion criterion. Participants will be recruited from primary health care clinics in Cape Town, South Africa, Windhoek in Namibia, Addis Ababa in Ethiopia, Banjul in The Gambia and Kampala in Uganda.
Number of Sites: Five sites
Study Duration: 3 years
Subject Duration: 18 months for TB cases, 2 months for non-TB cases
Objectives:
The overall objective of the study is to incorporate a six-marker serum signature into a multiplex UCP-LFA format, referred to as TransDot, for finger-prick blood testing. The end point of the study is the accuracy (sensitivity and specificity) of the UCP-LFA TransDot test on finger-prick blood for active TB and will be prospectively compared against gold standard composite diagnostic criteria (GeneXpert, MGIT culture, TB sputum smear, CXR, TB symptom screen and response to TB treatment).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 969
- Symptoms suggestive of TB disease: cough for more than two weeks with fever, malaise, weight loss, night sweats, haemoptysis, chest pain or loss of appetite.
- Willingness to give consent to take part in the study.
- Willingness to undergo HIV testing or be willing to have their HIV infection status disclosed to the study field workers.
- Eighteen years or older and aged 70 years or younger.
- Permanent residence in study area for less than 3 months or with no permanent address.
- Pregnancy or breastfeeding.
- HB<9g/l
- On TB treatment currently or in the last ninety days.
- HIV positive patients currently on INH prophylaxis, or in the last ninety days.
- Known quinolone or aminoglicozide antibiotic use reported in the past 60 days.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Test Set Trans-Dot point-of-care test Subsequent 300 participants to be used for the Test Set: * Fingerprick TransDot point-of-care test performed at field site after symptom screen and clinical evaluation and before CXR * Blood, sputum, saliva and urine collection for secondary objectives and repository
- Primary Outcome Measures
Name Time Method Diagnostic performance of the TransDot finger-prick test 3 years The primary outcome of interest will be accuracy, sensitivity and specificity of the TransDot finger-prick test when compared with the composite gold standard tests.
- Secondary Outcome Measures
Name Time Method POC TransDOT test versus lab-based tests 3 years To evaluate the agreement between the POC TransDot test and laboratory based ELISAs first (both on serum), and subsequently between POC TransDot (on fingerprick blood) and laboratory based TransDot (on serum).
TransDOT as treatment response marker 3 years To investigate the utility of a TransDot test at month 2 and month 6 as a marker of treatment response.
Identification of additional host marker signatures 3 years To identify additional host marker signatures that can be utilized for future improvement of diagnostic tests in the TransDot format or other point-of care tests that might become available in the future
Optimisation of ultra-sensitive TB culture techniques 3 years To refine and optimise ultra-sensitive TB culture techniques on sputum and compare these to standard techniques and the TransDot test results, at baseline and month 6.
Evaluation of the serum signature's underlying biological processes 3 years To evaluate the biological processes (cell-based immune profile and components) underlying the six-marker serum signature model during TB disease and treatment response. In parallel, the peripheral profile will compare this to the corresponding profile at the lung infection site.
Biomarker Biorepository Samples 3 years To collect appropriate additional host samples for future biomarker research
Trial Locations
- Locations (10)
Armauer Hansen Research Institute
🇪🇹Addis Ababa, Ethiopia
Medical Research Council The Gambia
🇬🇲Banjul, Gambia
European Research and Project Office GmbH
🇩🇪Saarbrücken, Saarland, Germany
University of Namibia
🇳🇦Windhoek, Namibia
Leiden University Medical Center (Academisch Ziekenhuis Leiden, LUMC)
🇳🇱Leiden, Netherlands
Makerere University
🇺🇬Kampala, Uganda
LINQ Management GmbH
🇩🇪Berlin, Germany
The European & Developing Countries Clinical Trials Partnership Association (EDCTP)
🇳🇱The Hague, South Holland, Netherlands
Stellenbosch University
🇿🇦Cape Town, Western Cape, South Africa
London School of Hygiene and Tropical Medicine
🇬🇧London, United Kingdom