Point-of-care Triage Test for Active Tuberculosis

NCT04232618 | Unknown DMC

• 1 other identifier: RIA2018D-2499
• Study Type: observational
• Target: 900
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Tuberculosis; Tuberculosis, Pulmonary

Outcome Measures

Primary Outcomes (1)

• Global diagnostic bio-signature for diagnosing active TB

  Accuracy of a point-of-care multi-biomarker test (POC-MBT) in active, pulmonary tuberculosis.

  4 years

Secondary Outcomes (1)

• Use of MBT for treatment response

  4 years

Study Arms (3)

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.

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.

Diagnostic Test: Multi-biomarker point-of-care test

Interventions

Multi-biomarker point-of-care test DIAGNOSTIC_TEST

Lateral flow device containing a combination of markers which have been shown to be associated with active tuberculosis.

Phase 1; Phase 2

Eligibility Criteria

• Age: 15 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants are recruited from known TB endemic areas across three African countries.

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• University of Stellenbosch: lead
• London School of Hygiene and Tropical Medicine: collaborator
• Makerere University: collaborator
• Find: collaborator
• Leiden University Medical Center: collaborator
• Medical Research Council Unit, The Gambia: collaborator
• LINQ Management GMBH: collaborator

Study Sites (1)

Stellenbosch University

Cape Town, Western Cape, 7505, South Africa

RECRUITING

Related Publications (3)

• 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.

  PMID: 29624071 BACKGROUND

• Tadesse 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.

  PMID: 22164256 BACKGROUND

• Richardson 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.

  PMID: 37400753 DERIVED

Related Links

• TB Statistics for South Africa

Biospecimen

Retention: SAMPLES WITH DNA

Finger stick capillary blood for POC test strip, Serum collection and storage, Whole blood collection for isolation of peripheral blood mononuclear cells (PBMCs), PAXgene collection for storage of mRNA, Sputum for testing and storage, Urine for storage

MeSH Terms

Conditions

Tuberculosis; Tuberculosis, Pulmonary

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, MBCHB; PhD

  University of Stellenbosch

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stephanus Malherbe, MBCHB, PhD

CONTACT

+27 21 938 9646; malherbe@sun.ac.za

Bronwyn Smith, MSc

CONTACT

+27 21 938 9646; bronwynt@sun.ac.za

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 6 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Executive Head of Department of Biomedical Sciences

Study Record Dates

• First Submitted: November 26, 2019
• First Posted: January 18, 2020
• Study Start: November 5, 2020
• Primary Completion: September 1, 2023
• Study Completion: March 1, 2024
• Last Updated: January 25, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (1)