Clinical trial NCT04232618: Point-of-care Triage Test for Active Tuberculosis
Official title: Field Evaluation of a Point-of-care Triage Test for Active Tuberculosis
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Tuberculosis
Tuberculosis, Pulmonary
Lead sponsor: University of Stellenbosch
Sponsor class: OTHER
Collaborators: name: London School of Hygiene and Tropical Medicine
name: Makerere University
name: Find
name: Leiden University Medical Center
name: Medical Research Council Unit, The Gambia
name: LINQ Management GMBH
First posted: 2020-01-18
Enrollment: 900
Sex: ALL
Minimum age (years): 15
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants are recruited from known TB endemic areas across three African countries.

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.

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.

Eligibility criteria: Inclusion Criteria:

1. Aged 12 to 70 years.
2. 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.
3. Participants aged ≥18 years-old: Willing to give informed consent to take part in the study, including

   1. Willingness to undergo HIV testing and be willing to have their HIV infection status disclosed to the study field workers.
   2. Willingness to have study samples stored indefinitely.
4. Participants aged ≥12 and \<18 years:

   1. Accompanied by a parent or legal guardian/caregiver/representative who is willing to provide informed consent for study procedures as above, and
   2. 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.

Exclusion Criteria:

1. Stable permanent residence in study area for less than 3 months; no permanent address or planned relocation in the next six months.
2. Pregnancy or breastfeeding.
3. Hb \< 9g/l.
4. Current systemic steroid use or immune suppression therapy in the past four weeks.
5. On TB treatment or Isoniazid Preventive Treatment (IPT) currently or in the last ninety days.
6. Known quinolone or aminoglycoside antibiotic use reported in the past 60 days.
7. 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).
8. Participants aged ≥12 and \<18 years:

   1. Either the parent/guardian is willing to give informed consent or the participant is unwilling to give informed assent.
   2. 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).

Primary outcomes:
measure: Global diagnostic bio-signature for diagnosing active TB
timeFrame: 4 years
Secondary outcomes:
measure: Use of MBT for treatment response
timeFrame: 4 years
Other outcomes:
Locations:
city: Cape Town
country: South Africa
facility: Stellenbosch University
state: Western Cape
Study officials:
affiliation: University of Stellenbosch
name: Gerhard Walzl, MBCHB; PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.