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

Sponsor

Prof Gerhard Walzl (Other)

Overall Status

Unknown status

CT.gov ID

NCT03350048

Collaborator

Armauer Hansen Research Institute, Ethiopia (Other), Medical Research Council Unit, The Gambia (Other), Leiden University Medical Center (Other), Makerere University (Other), London School of Hygiene and Tropical Medicine (Other), European and Developing Countries Clinical Trials Partnership (EDCTP) (Other), LINQ Management GMBH (Other), European Research and Project Office GmbH (Other)

800

Enrollment

Locations

37.9

Anticipated Duration (Months)

Patients Per Site

2.1

Patients Per Site Per Month

Study Details

Study Description

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	Phase
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).

Study Design

Study Type:

Observational

Anticipated 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

Anticipated Primary Completion Date :

Jun 30, 2019

Anticipated Study Completion Date :

Jun 30, 2019

Arms and Interventions

Arm	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.

Arm

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.

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Armauer Hansen Research Institute	Addis Ababa		Ethiopia
2	Medical Research Council The Gambia	Banjul		Gambia
3	European Research and Project Office GmbH	Saarbrücken	Saarland	Germany	66123
4	LINQ Management GmbH	Berlin		Germany	14057
5	University of Namibia	Windhoek		Namibia	13301
6	The European & Developing Countries Clinical Trials Partnership Association (EDCTP)	The Hague	South Holland	Netherlands	2593 HW
7	Leiden University Medical Center (Academisch Ziekenhuis Leiden, LUMC)	Leiden		Netherlands	2333 ZA
8	Stellenbosch University	Cape Town	Western Cape	South Africa	7505
9	Makerere University	Kampala		Uganda
10	London School of Hygiene and Tropical Medicine	London		United Kingdom	WC1E 7HT