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Evaluation of Host Biomarker-based Point-of-care Tests for Targeted Screening for Active TB (ScreenTB)

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ClinicalTrials.gov Identifier: NCT03350048
Recruitment Status : Enrolling by invitation
First Posted : November 22, 2017
Last Update Posted : April 17, 2019
Sponsor:
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
European Research and Project Office GmbH
Information provided by (Responsible Party):
Prof Gerhard Walzl, University of Stellenbosch

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.


Condition or disease Intervention/treatment
Pulmonary Tuberculosis Diagnostic Test: Trans-Dot point-of-care test

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).


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Study Type : Observational
Estimated Enrollment : 800 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Evaluation of Host Biomarker-based Point-of-care Tests for Targeted Screening for Active TB
Actual Study Start Date : May 2, 2016
Estimated Primary Completion Date : June 30, 2019
Estimated Study Completion Date : June 30, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Tuberculosis

Group/Cohort Intervention/treatment
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
Diagnostic Test: Trans-Dot point-of-care 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.





Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. POC TransDOT test versus lab-based tests [ Time Frame: 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).

  2. TransDOT as treatment response marker [ Time Frame: 3 years ]
    To investigate the utility of a TransDot test at month 2 and month 6 as a marker of treatment response.

  3. Identification of additional host marker signatures [ Time Frame: 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

  4. Evaluation of the serum signature's underlying biological processes [ Time Frame: 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.

  5. Optimisation of ultra-sensitive TB culture techniques [ Time Frame: 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.

  6. Biomarker Biorepository Samples [ Time Frame: 3 years ]
    To collect appropriate additional host samples for future biomarker research


Biospecimen Retention:   Samples With DNA
  • Blood
  • Sputum
  • Urine
  • Saliva


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Sampling Method:   Non-Probability Sample
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.

Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03350048


Locations
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Ethiopia
Armauer Hansen Research Institute
Addis Ababa, Ethiopia
Gambia
Medical Research Council The Gambia
Banjul, Gambia
Germany
European Research and Project Office GmbH
Saarbrücken, Saarland, Germany, 66123
LINQ Management GmbH
Berlin, Germany, 14057
Namibia
University of Namibia
Windhoek, Namibia, 13301
Netherlands
The European & Developing Countries Clinical Trials Partnership Association (EDCTP)
The Hague, South Holland, Netherlands, 2593 HW
Leiden University Medical Center (Academisch Ziekenhuis Leiden, LUMC)
Leiden, Netherlands, 2333 ZA
South Africa
Stellenbosch University
Cape Town, Western Cape, South Africa, 7505
Uganda
Makerere University
Kampala, Uganda
United Kingdom
London School of Hygiene and Tropical Medicine
London, United Kingdom, WC1E 7HT
Sponsors and Collaborators
Prof Gerhard Walzl
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
European Research and Project Office GmbH
Investigators
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Principal Investigator: Gerhard Walzl, PhD, MD Head of Department of Biomedical Sciences
  Study Documents (Full-Text)

Documents provided by Prof Gerhard Walzl, University of Stellenbosch:

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Responsible Party: Prof Gerhard Walzl, Prof, University of Stellenbosch
ClinicalTrials.gov Identifier: NCT03350048     History of Changes
Other Study ID Numbers: N16/05/070
First Posted: November 22, 2017    Key Record Dates
Last Update Posted: April 17, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Prof Gerhard Walzl, University of Stellenbosch:
Tuberculosis
Point-of-care test
Diagnostics
Biomarkers

Additional relevant MeSH terms:
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Tuberculosis
Tuberculosis, Pulmonary
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections