TuberculosisTriageTBNCT04232618
Point-of-care Triage Test for Active Tuberculosis
An observational study of Tuberculosis and Tuberculosis, Pulmonary, run by University of Stellenbosch at 1 site in South Africa.
Trial summary
Background: Tuberculosis (TB) is a bacterial lung infection leaving 3.6 million people undiagnosed each year. Thirty percent of infected people do not receive treatment due to failure to receive diagnostic testing or being lost to follow-up between testing and availability of results. Read more about this study
- Who is it for?
- Ages 15 to 70 years
- Conditions the study is for
- Tuberculosis, Tuberculosis, Pulmonary
- What is being tested?
- Multi-biomarker point-of-care test
- How many people
- 900 participants
- Where
- 1 siteSouth Africa
- Study dates
- 5 Nov 2020to Mar 2024
- How long will I take part?
- 6 Months
- 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 15 to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Participants are recruited from known TB endemic areas across three African countries.
Who may be able to join
- Aged 12 to 70 years.
- Symptoms suggestive of TB disease: cough for ≥ two weeks plus at least one of the following: fever, malaise, weight loss, night sweats, haemoptysis, chest pain or loss of appetite.
- Participants aged ≥18 years-old: Willing to give informed consent to take part in the study, including
- Willingness to undergo HIV testing and be willing to have their HIV infection status disclosed to the study field workers.
- Willingness to have study samples stored indefinitely.
- Participants aged ≥12 and <18 years:
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- Accompanied by a parent or legal guardian/caregiver/representative who is willing to provide informed consent for study procedures as above, and
- The child is willing to give informed assent for study procedures as above and the attending research staff member is satisfied that the participant understands the study satisfactorily.
- Participants who had previous TB, extra-pulmonary TB in addition to pulmonary TB, drug resistance detected on GeneXpert® Ultra or culture, or other concomitant diseases will not be excluded from enrolment. People living with, and without, HIV will be enrolled.
Who cannot join
- Stable permanent residence in study area for less than 3 months; no permanent address or planned relocation in the next six months.
- Pregnancy or breastfeeding.
- Hb < 9g/l.
- Current systemic steroid use or immune suppression therapy in the past four weeks.
- On TB treatment or Isoniazid Preventive Treatment (IPT) currently or in the last ninety days.
- Known quinolone or aminoglycoside antibiotic use reported in the past 60 days.
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- Participants aged ≥18 years-old: Unable to provide informed consent (eg due to mental impairment), or are deemed by the attending research staff member as unable to complete study procedures (eg. due to substance abuse affecting the participant's level of function).
- Participants aged ≥12 and <18 years:
- Either the parent/guardian is willing to give informed consent or the participant is unwilling to give informed assent.
- Both the parent/guardian and the child are willing to provide consent and assent, but in the attending researcher's opinion there is a problem with the validity of the consent (eg. because of suspected mental impairment) or with completion of study procedures (eg. because of substance abuse of parent or child).
Trial locations and contacts
1 site in 1 country.
South Africa1 site, 1 recruiting
- Recruiting
Stellenbosch University
Cape Town, Western Cape, 7505
Stephanus Dr Malherbe, MBChb; PhD, 021 938 9666, malherbe@sun.ac.za
About this study
Official title: Field Evaluation of a Point-of-care Triage Test for Active Tuberculosis
Background:
Tuberculosis (TB) is a bacterial lung infection leaving 3.6 million people undiagnosed each year. Thirty percent of infected people do not receive treatment due to failure to receive diagnostic testing or being lost to follow-up between testing and availability of results.
Read more
Objective:
To refine and field-validate a point-of-care (POC) finger stick blood test for use worldwide to triage for active TB.
Eligibility:
Persons aged 12 - 70 years with symptoms suggestive of TB disease
Study design:
Participants will be screened with:
Medical history Physical exam HIV test, diabetes screening Blood (finger stick and venous), sputum and urine collection Chest X-ray TB positive participants will receive treatment from the National TB Program at Community Health Centres and clinics.
Read the detailed description
This study aims to make widely available an inexpensive, easy to use point-of-care finger stick test to triage patients presenting with signs and symptoms consistent with active TB. From previous experience in EDCTP-funded studies, approximately 30% of such patients test positive for TB, with the vast majority having respiratory illnesses other than active TB, including acute upper or lower respiratory tract infections or exacerbations of chronic obstructive pulmonary disease. The proposed finger stick test is designed, with the aim of use, as a TB rule out test such that resources required for further testing can be used with more efficiency.
The majority (60%) of suspected TB cases are seen at public health facilities, however many facilities in high TB prevalence areas still do not have access to efficient TB diagnostic services due to logistical and financial constraints that plague these settings. Currently available diagnostics include radiological and microbiological testing, though each has drawbacks for use in primary care facilities.
The TriageTB consortium will be evaluating combinations of biomarkers in samples from African and Non-African individuals suspected of having TB in order to identify the optimal biomarker signature for global identification of patients with high likelihood of TB. A device has been developed, which measures a combination of biomarkers in finger stick capillary blood and has been validated in the laboratory setting. Previous EDCTP-funded projects identified a promising 6-marker biosignature which has been shown to have potential for being reduced to a 3- or 4- marker signature. The 3-marker signature has the added benefit of potential for treatment monitoring applications. A triage test as proposed here would significantly speed up and streamline diagnostic approaches in resource-limited settings.
- Conditions
- Tuberculosis, Tuberculosis, Pulmonary
- Being tested
- Multi-biomarker point-of-care test
- Medical subject headings
- Tuberculosis, Tuberculosis, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Multi-biomarker point-of-care testDiagnostic test
Lateral flow device containing a combination of markers which have been shown to be associated with active tuberculosis.
| Study group | Role | What they receive |
|---|---|---|
| FIND cohort | Evaluation of biomarkers in serum samples from 500 people with suspected TB from non-African countries provided by FIND diagnostic biorepository. | |
| Phase 1 | Evaluate the basic 3-marker multi-biomarker test (MBT) signature in 150 participants across three African sites. This will be used to lock down the final MBT signature to be used in the next phase of testing. Receives: Diagnostic Test: Multi-biomarker point-of-care test | |
| Phase 2 | Enrolment of 750 participants across three African sites using the locked down MBT signature from phase 1. Receives: Diagnostic Test: Multi-biomarker point-of-care test |
What is being measured
The primary outcome is the main question the study is designed to answer.
Global diagnostic bio-signature for diagnosing active TB
Accuracy of a point-of-care multi-biomarker test (POC-MBT) in active, pulmonary tuberculosis.
Measured: 4 years
Secondary outcomes (1)
Use of MBT for treatment response
Accuracy of the point-of-care multi-biomarker test as an indicator of tuberculosis treatment outcome.
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2020
- Study start5 Nov 2020
- Primary completionSep 2023 (estimated)
- Study completionMar 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for 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
- 900 participants (estimated)
- Target duration
- 6 Months
Sponsor and investigators
- Lead sponsor
- University of Stellenbosch
- Sponsor type
- University, hospital or other
- Collaborators
- London School of Hygiene and Tropical Medicine, Makerere University, Find, Leiden University Medical Center, Medical Research Council Unit, The Gambia, LINQ Management GMBH
- Responsible party
- Principal investigator, Prof Gerhard Walzl, University of Stellenbosch
- Investigators
- Gerhard Walzl, MBCHB; PhD, Principal investigator, University of Stellenbosch
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04232618
- Sponsor's protocol ID
- RIA2018D-2499
- Acronym
- TriageTB
- Status last verified
- Jan 2022
- First submitted
- 26 Nov 2019
- Last updated
- 25 Jan 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Suliman S, Thompson EG, Sutherland J, Weiner J 3rd, Ota MOC, Shankar S, Penn-Nicholson A, Thiel B, Erasmus M, Maertzdorf J, Duffy FJ, Hill PC, Hughes EJ, Stanley K, Downing K, Fisher ML, Valvo J, Parida SK, van der Spuy G, Tromp G, Adetifa IMO, Donkor S, Howe R, Mayanja-Kizza H, Boom WH, Dockrell HM, Ottenhoff THM, Hatherill M, Aderem A, Hanekom WA, Scriba TJ, Kaufmann SHE, Zak DE, Walzl G; GC6-74 cohort study team, The ACS cohort study team. Four-Gene Pan-African Blood Signature Predicts Progression to Tuberculosis. Am J Respir Crit Care Med. 2018 May 1;197(9):1198-1208. doi: 10.1164/rccm.201711-2340OC.
PubMed 29624071Tadesse T, Demissie M, Berhane Y, Kebede Y, Abebe M. Two-thirds of smear-positive tuberculosis cases in the community were undiagnosed in Northwest Ethiopia: population based cross-sectional study. PLoS One. 2011;6(12):e28258. doi: 10.1371/journal.pone.0028258. Epub 2011 Dec 2.
PubMed 22164256Richardson TR, Smith B, Malherbe ST, Shaw JA, Noor F, MacDonald C, van der Spuy GD, Stanley K, Carstens A, Fisher TL, van Rensburg I, Flinn M, Snyders C, Johnson I, Fransman B, Dockrell H, Thwaites G, Thuong NTT, Schacht C, Mayanja-Kizza H, Nsereko M, Tjon Kon Fat EM, Corstjens PLAM, Geluk A, Ruhwald M, Penn-Nicholson A, Chegou NN, Sutherland J, Walzl G; TrENDx consortium. Field evaluation of a point-of-care triage test for active tuberculosis (TriageTB). BMC Infect Dis. 2023 Jul 3;23(1):447. doi: 10.1186/s12879-023-08342-5.
PubMed 37400753
Study at a glance
From the registry record, last updated by the sponsor on 25 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Field Evaluation of a Point-of-care Triage Test for Active Tuberculosis
- ClinicalTrials.gov ID
- NCT04232618
- Acronym / sponsor ID
- TriageTB / RIA2018D-2499
- Conditions
- Tuberculosis, Tuberculosis, Pulmonary
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 900 participants (estimated)
- Lead sponsor
- University of StellenboschUniversity, hospital or other
- Collaborators
- London School of Hygiene and Tropical Medicine, Makerere University, Find, Leiden University Medical Center, Medical Research Council Unit, The Gambia, LINQ Management GMBH
- Study start
- 5 Nov 2020 (actual)
- Primary completion
- Sep 2023 (estimated)
- Study completion
- Mar 2024 (estimated)
- First posted
- 18 Jan 2020 (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.
Background:
Tuberculosis (TB) is a bacterial lung infection leaving 3.6 million people undiagnosed each year. Thirty percent of infected people do not receive treatment due to failure to receive diagnostic testing or being lost to follow-up between testing and availability of results.
Objective:
To refine and field-validate a point-of-care (POC) finger stick blood test for use worldwide to triage for active TB.
Eligibility:
Persons aged 12 - 70 years with symptoms suggestive of TB disease
Study design:
Participants will be screened with:
Medical history Physical exam HIV test, diabetes screening Blood (finger stick and venous), sputum and urine collection Chest X-ray TB positive participants will receive treatment from the National TB Program at Community Health Centres and clinics.
Detailed description
This study aims to make widely available an inexpensive, easy to use point-of-care finger stick test to triage patients presenting with signs and symptoms consistent with active TB. From previous experience in EDCTP-funded studies, approximately 30% of such patients test positive for TB, with the vast majority having respiratory illnesses other than active TB, including acute upper or lower respiratory tract infections or exacerbations of chronic obstructive pulmonary disease. The proposed finger stick test is designed, with the aim of use, as a TB rule out test such that resources required for further testing can be used with more efficiency.
The majority (60%) of suspected TB cases are seen at public health facilities, however many facilities in high TB prevalence areas still do not have access to efficient TB diagnostic services due to logistical and financial constraints that plague these settings. Currently available diagnostics include radiological and microbiological testing, though each has drawbacks for use in primary care facilities.
The TriageTB consortium will be evaluating combinations of biomarkers in samples from African and Non-African individuals suspected of having TB in order to identify the optimal biomarker signature for global identification of patients with high likelihood of TB. A device has been developed, which measures a combination of biomarkers in finger stick capillary blood and has been validated in the laboratory setting. Previous EDCTP-funded projects identified a promising 6-marker biosignature which has been shown to have potential for being reduced to a 3- or 4- marker signature. The 3-marker signature has the added benefit of potential for treatment monitoring applications. A triage test as proposed here would significantly speed up and streamline diagnostic approaches in resource-limited settings.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 6 Months
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| FIND cohort | – | –Evaluation of biomarkers in serum samples from 500 people with suspected TB from non-African countries provided by FIND diagnostic biorepository. |
| Phase 1 | – | Diagnostic Test: Multi-biomarker point-of-care testEvaluate the basic 3-marker multi-biomarker test (MBT) signature in 150 participants across three African sites. This will be used to lock down the final MBT signature to be used in the next phase of testing. |
| Phase 2 | – | Diagnostic Test: Multi-biomarker point-of-care testEnrolment of 750 participants across three African sites using the locked down MBT signature from phase 1. |
Who may qualify
- Ages
- 15 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Participants are recruited from known TB endemic areas across three African countries.
Key inclusion criteria (9 listed)
- Aged 12 to 70 years.
- Symptoms suggestive of TB disease: cough for ≥ two weeks plus at least one of the following: fever, malaise, weight loss, night sweats, haemoptysis, chest pain or loss of appetite.
- Participants aged ≥18 years-old: Willing to give informed consent to take part in the study, including
- Participants aged ≥12 and <18 years:
- Participants who had previous TB, extra-pulmonary TB in addition to pulmonary TB, drug resistance detected on GeneXpert® Ultra or culture, or other concomitant diseases will not be excluded from enrolment. People living with, and without, HIV will be enrolled.
Key exclusion criteria (10 listed)
- Stable permanent residence in study area for less than 3 months; no permanent address or planned relocation in the next six months.
- Pregnancy or breastfeeding.
- Hb < 9g/l.
- Current systemic steroid use or immune suppression therapy in the past four weeks.
- On TB treatment or Isoniazid Preventive Treatment (IPT) currently 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 |
|---|---|---|
| Multi-biomarker point-of-care testLateral flow device containing a combination of markers which have been shown to be associated with active tuberculosis. | Diagnostic test | Phase 1, Phase 2 |
Primary outcome
Global diagnostic bio-signature for diagnosing active TB
Time frame: 4 years
Accuracy of a point-of-care multi-biomarker test (POC-MBT) in active, pulmonary tuberculosis.
1 secondary outcome
Use of MBT for treatment response
Time frame: 4 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jan 2022.
- Background: PubMed 29624071Suliman S, Thompson EG, Sutherland J, Weiner J 3rd, Ota MOC, Shankar S, Penn-Nicholson A, Thiel B, Erasmus M, Maertzdorf J, Duffy FJ, Hill PC, Hughes EJ, Stanley K, Downing K, Fisher ML, Valvo J, Parida SK, van der Spuy G, Tromp G, Adetifa IMO, Donkor S, Howe R, Mayanja-Kizza H, Boom WH, Dockrell HM, Ottenhoff THM, Hatherill M, Aderem A, Hanekom WA, Scriba TJ, Kaufmann SHE, Zak DE, Walzl G; GC6-74 cohort study team, The ACS cohort study team. Four-Gene Pan-African Blood Signature Predicts Progression to Tuberculosis. Am J Respir Crit Care Med. 2018 May 1;197(9):1198-1208. doi: 10.1164/rccm.201711-2340OC.
- Background: PubMed 22164256Tadesse T, Demissie M, Berhane Y, Kebede Y, Abebe M. Two-thirds of smear-positive tuberculosis cases in the community were undiagnosed in Northwest Ethiopia: population based cross-sectional study. PLoS One. 2011;6(12):e28258. doi: 10.1371/journal.pone.0028258. Epub 2011 Dec 2.
- Derived from this study: PubMed 37400753Richardson TR, Smith B, Malherbe ST, Shaw JA, Noor F, MacDonald C, van der Spuy GD, Stanley K, Carstens A, Fisher TL, van Rensburg I, Flinn M, Snyders C, Johnson I, Fransman B, Dockrell H, Thwaites G, Thuong NTT, Schacht C, Mayanja-Kizza H, Nsereko M, Tjon Kon Fat EM, Corstjens PLAM, Geluk A, Ruhwald M, Penn-Nicholson A, Chegou NN, Sutherland J, Walzl G; TrENDx consortium. Field evaluation of a point-of-care triage test for active tuberculosis (TriageTB). BMC Infect Dis. 2023 Jul 3;23(1):447. doi: 10.1186/s12879-023-08342-5.
- TB Statistics for South AfricaLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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, MBCHB; PhD principal investigator
University of Stellenbosch
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Tuberculosis and Tuberculosis, Pulmonary, run by University of Stellenbosch at 1 site in South Africa.
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 9 inclusion and 10 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: status not confirmed, as of the sponsor's last update on 25 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Africa. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Stephanus Malherbe, MBCHB, PhD (+27 21 938 9646, malherbe@sun.ac.za), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Global diagnostic bio-signature for diagnosing active TB (time frame: 4 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04232618, which also lists 3 linked publications.
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 25 Jan 2022.