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

NCT03350048 | Completed

• 1 other identifier: N16/05/070
• Study Type: observational
• Target: 969
• Locations: 8 countries
• Sites: 10

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.

Conditions

Pulmonary Tuberculosis

Keywords

Tuberculosis; Point-of-care test; Diagnostics; Biomarkers

Outcome Measures

Primary Outcomes (1)

• 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.

  3 years

Secondary Outcomes (6)

• POC TransDOT test versus lab-based tests

  3 years

• TransDOT as treatment response marker

  3 years

• Identification of additional host marker signatures

  3 years

• Evaluation of the serum signature's underlying biological processes

  3 years

• Optimisation of ultra-sensitive TB culture techniques

  3 years

Study Arms (2)

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

Interventions

Trans-Dot point-of-care test DIAGNOSTIC_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.

Test Set

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Prof Gerhard Walzl: lead
• Armauer Hansen Research Institute, Ethiopia: collaborator
• Medical Research Council Unit, The Gambia: collaborator
• Leiden University Medical Center: collaborator
• Makerere University: collaborator
• London School of Hygiene and Tropical Medicine: collaborator
• European and Developing Countries Clinical Trials Partnership (EDCTP): collaborator
• LINQ Management GMBH: collaborator

Study Sites (10)

Armauer Hansen Research Institute

Addis Ababa, Ethiopia

Location

European Research and Project Office GmbH

Saarbrücken, Saarland, 66123, Germany

Location

LINQ Management GmbH

Berlin, 14057, Germany

Location

University of Namibia

Windhoek, 13301, Namibia

Location

The European & Developing Countries Clinical Trials Partnership Association (EDCTP)

The Hague, South Holland, 2593 HW, Netherlands

Location

Leiden University Medical Center (Academisch Ziekenhuis Leiden, LUMC)

Leiden, 2333 ZA, Netherlands

Location

Stellenbosch University

Cape Town, Western Cape, 7505, South Africa

Location

Medical Research Council The Gambia

Banjul, The Gambia

Location

Makerere University

Kampala, Uganda

Location

London School of Hygiene and Tropical Medicine

London, WC1E 7HT, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITH DNA

* Blood * Sputum * Urine * Saliva

MeSH Terms

Conditions

Tuberculosis, Pulmonary; Tuberculosis

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Gerhard Walzl, PhD, MD

  Head of Department of Biomedical Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof

Study Record Dates

• First Submitted: November 17, 2017
• First Posted: November 22, 2017
• Study Start: April 1, 2016
• Primary Completion: April 30, 2019
• Study Completion: July 31, 2020
• Last Updated: February 1, 2023

Record last verified: 2023-01

Locations

ET (1); DE (2); TH (1); GB (1); NL (2); NA (1); ZA (1); UG (1)