Pulmonary TuberculosisScreenTBNCT03350048
Evaluation of Host Biomarker-based Point-of-care Tests for Targeted Screening for Active TB
An observational study of Pulmonary Tuberculosis, run by Prof Gerhard Walzl at 10 sites in 8 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Pulmonary Tuberculosis
- What is being tested?
- Trans-Dot point-of-care test
- How many people
- 969 participants
- Where
- 10 sitesin 8 countries
- Study dates
- 1 Apr 2016to 31 Jul 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Adult, Older adult
Study population: Adult participants with suspected active TB disease will be recruited in South Africa, the Gambia, Uganda, Namibia and Ethiopia. Each site will recruit approximately 160 participants with suspected TB, until the desired overall total of about 800 participants is reached. In South Africa, up to 300 participants will be recruited from primary health care clinics (Adriaanse, Elsiesriver, Uitsig, Ravensmead, Fisantekraal, Durbanville and Dunoon) in Cape Town. Patients presenting to the health care facility with symptomatic pulmonary disease and a high likelihood of having tuberculosis will be enrolled and followed up for outcome classification. Participants who had previous TB, extra-pulmonary TB in addition to pulmonary TB, drug resistance detected on GeneXpert or culture or other concomitant diseases, will not be excluded from enrolment. Both HIV positive and HIV negative individuals will be enrolled.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
10 sites in 8 countries.
10 sites in 8 countries
Germany2 sites
LINQ Management GmbH
Berlin, 14057
European Research and Project Office GmbH
Saarbrücken, Saarland, 66123
Netherlands2 sites
Leiden University Medical Center (Academisch Ziekenhuis Leiden, LUMC)
Leiden, 2333 ZA
The European & Developing Countries Clinical Trials Partnership Association (EDCTP)
The Hague, South Holland, 2593 HW
Namibia1 site
University of Namibia
Windhoek, 13301
United Kingdom1 site
London School of Hygiene and Tropical Medicine
London, WC1E 7HT
About this study
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.
Read more
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.
Read the 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).
- Conditions
- Pulmonary Tuberculosis
- Being tested
- Trans-Dot point-of-care test
- Keywords
- Tuberculosis, Point-of-care test, Diagnostics, Biomarkers
- Medical subject headings
- Tuberculosis, Pulmonary, Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trans-Dot point-of-care testDiagnostic test
Training set participants will be recruited and receive investigations for TB. Blood samples will also be collected from them for performance of ELISAs and laboratory-based TransDot tests. These blood samples will be drawn at baseline, week 8 and week 24 at end of treatment for confirmed TB cases and at baseline for non-TB cases.
Test set participants will be recruited and receive investigations for TB. A POC TransDot test will be performed on fingerprick blood at baseline, and at week 8 and week 24 in participants on TB treatment, as well as a laboratory based TransDot test on serum at baseline. The week 8 and week 24 TransDot tests will be used to investigate the test's utility as an indicator of treatment response.
| Study group | Role | What they receive |
|---|---|---|
| Training Set | First 500 participants recruited for the Training Set: * Blood collection for optimization and validation (vs ELISA) of TransDot point-of-care test at LUMC and later for lab-based TransDot at local site laboratory * Blood, sputum, saliva and urine collection for secondary objectives and repository | |
| Test Set | 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 Receives: Diagnostic Test: Trans-Dot point-of-care test |
What is being measured
The primary outcome is the main question the study is designed to answer.
Diagnostic performance of the TransDot finger-prick test
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.
Measured: 3 years
Secondary outcomes (6)
POC TransDOT test versus lab-based tests
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).
Measured: 3 years
TransDOT as treatment response marker
To investigate the utility of a TransDot test at month 2 and month 6 as a marker of treatment response.
Measured: 3 years
Identification of additional host marker signatures
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
Measured: 3 years
Evaluation of the serum signature's underlying biological processes
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.
Measured: 3 years
Optimisation of ultra-sensitive TB culture techniques
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.
Measured: 3 years
Biomarker Biorepository Samples
To collect appropriate additional host samples for future biomarker research
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2017
- Study start1 Apr 2016
- Primary completion30 Apr 2019
- Study completion31 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary TuberculosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 969 participants (actual)
Sponsor and investigators
- Lead sponsor
- Prof Gerhard Walzl
- Sponsor type
- University, hospital or other
- Collaborators
- Armauer Hansen Research Institute, Ethiopia, Medical Research Council Unit, The Gambia, Leiden University Medical Center, Makerere University, London School of Hygiene and Tropical Medicine, European and Developing Countries Clinical Trials Partnership (EDCTP), LINQ Management GMBH
- Responsible party
- Sponsor-investigator, Prof Gerhard Walzl, University of Stellenbosch
- Investigators
- Gerhard Walzl, PhD, MD, Principal investigator, Head of Department of Biomedical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03350048
- Sponsor's protocol ID
- N16/05/070
- Acronym
- ScreenTB
- Status last verified
- Jan 2023
- First submitted
- 17 Nov 2017
- Last updated
- 1 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Host Biomarker-based Point-of-care Tests for Targeted Screening for Active TB
- ClinicalTrials.gov ID
- NCT03350048
- Acronym / sponsor ID
- ScreenTB / N16/05/070
- Conditions
- Pulmonary Tuberculosis
- Keywords
- Tuberculosis, Point-of-care test, Diagnostics, Biomarkers
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 969 participants (actual)
- Lead sponsor
- Prof Gerhard WalzlUniversity, hospital or other
- Collaborators
- Armauer Hansen Research Institute, Ethiopia, Medical Research Council Unit, The Gambia, Leiden University Medical Center, Makerere University, London School of Hygiene and Tropical Medicine, European and Developing Countries Clinical Trials Partnership (EDCTP), LINQ Management GMBH
- Study start
- 1 Apr 2016 (actual)
- Primary completion
- 30 Apr 2019 (actual)
- Study completion
- 31 Jul 2020 (actual)
- First posted
- 22 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Training Set | – | –First 500 participants recruited for the Training Set: * Blood collection for optimization and validation (vs ELISA) of TransDot point-of-care test at LUMC and later for lab-based TransDot at local site laboratory * Blood, sputum, saliva and urine collection for secondary objectives and repository |
| Test Set | – | Diagnostic Test: Trans-Dot point-of-care testSubsequent 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 |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- Adult participants with suspected active TB disease will be recruited in South Africa, the Gambia, Uganda, Namibia and Ethiopia. Each site will recruit approximately 160 participants with suspected TB, until the desired overall total of about 800 participants is reached. In South Africa, up to 300 participants will be recruited from primary health care clinics (Adriaanse, Elsiesriver, Uitsig, Ravensmead, Fisantekraal, Durbanville and Dunoon) in Cape Town. Patients presenting to the health care facility with symptomatic pulmonary disease and a high likelihood of having tuberculosis will be enrolled and followed up for outcome classification. Participants who had previous TB, extra-pulmonary TB in addition to pulmonary TB, drug resistance detected on GeneXpert or culture or other concomitant diseases, will not be excluded from enrolment. Both HIV positive and HIV negative individuals will be enrolled.
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Trans-Dot point-of-care testTraining set participants will be recruited and receive investigations for TB. Blood samples will also be collected from them for performance of ELISAs and laboratory-based TransDot tests. These blood samples will be drawn at baseline, week 8 and week 24 at end of treatment for confirmed TB cases and at baseline for non-TB cases. Test set participants will be recruited and receive investigations for TB. A POC TransDot test will be performed on fingerprick blood at baseline, and at week 8 and week 24 in participants on TB treatment, as well as a laboratory based TransDot test on serum at baseline. The week 8 and week 24 TransDot tests will be used to investigate the test's utility as an indicator of treatment response. | Diagnostic test | Test Set |
Primary outcome
Diagnostic performance of the TransDot finger-prick test
Time frame: 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.
6 secondary outcomes
POC TransDOT test versus lab-based tests
Time frame: 3 years
TransDOT as treatment response marker
Time frame: 3 years
Identification of additional host marker signatures
Time frame: 3 years
Evaluation of the serum signature's underlying biological processes
Time frame: 3 years
Optimisation of ultra-sensitive TB culture techniques
Time frame: 3 years
Biomarker Biorepository Samples
Time frame: 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gerhard Walzl, PhD, MD principal investigator
Head of Department of Biomedical Sciences
10 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Pulmonary Tuberculosis, run by Prof Gerhard Walzl at 10 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Germany, Netherlands, Ethiopia, Namibia, South Africa and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Diagnostic performance of the TransDot finger-prick test (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Feb 2023.