Predicting the Future: Incipient Tuberculosis

NCT04825327 | Completed

• 1 other identifier: RIA2018D-2509
• Study Type: observational
• Target: 3,016
• Locations: 3 countries
• Sites: 3

Brief Summary

The investigators will study, prospectively, if contacts (household or close contacts) of tuberculosis (TB) patients with high C-reactive protein (CRP), low hemoglobin (Hb) levels, and a positive Xpert Host Response (HR) cartridge result develop active TB within 12 months. They will also investigate if there is a correlation between progressing to active TB within 12 months and having high levels of the iron homeostasis markers (Hepcidin, Ferritin and Transferrin). Identified index cases who agree to participate will refer their household or close contacts to also join the study. These contacts will be tested for TB and only contacts who are negative will be enrolled and followed-up at 6 months and 12 months. Blood samples will be collected at baseline and 6 months for testing. During the study period, TB testing will be done on contacts who meet symptoms criteria. At 12 months, all contacts will undergo a chest x-ray to assist in the diagnosis of TB. PreFIT will target people aged 12 to 60 years of age and both HIV negative and positive. 1515 trial participants will be recruited at Stellenbosch University in South Africa, 1515 at Fundaçao Manhiça in Mozambique and 1010 at Makerere University in Uganda, respectively.

Conditions

Tuberculosis

Keywords

Diagnostic accuracy; Host response cartridge; TB contacts; Incipient TB; Point-of-care-testing

Outcome Measures

Primary Outcomes (1)

• Predictive accuracy of each assay for incident TB occurring over a 12-month period from enrolment.

  Predictive accuracy is operationalized in the following metrics: sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), for each assay at a predefined cut-off value for a positive versus negative test result.

  12 months

Secondary Outcomes (3)

• Assay turnaround time and error rates

  30 months

• Accuracy of predictive algorithms

  12 months

• Diagnostic cost

  12 months

Eligibility Criteria

• Age: 12 Years - 60 Years
• Sex: all
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Presumptive TB patients diagnosed by the TB programme or as part of an ongoing study with bacteriologically confirmed (smear microscopy, Xpert, Ultra, culture, or MTBDRplus) active TB, and any person who has been exposed to the presumptive TB patients will be recruited from primary care clinics. The presumptive TB patients are enrolled to find and select the exposed individuals who will constitute the cohort.

You may qualify if:

• Index cases
• ≥18 years old
• Willing to provide the contact information of people who meet the definition of contacts, or willing to refer those people (which make require the distribution of study pamphlets) so that may contact study staff
• Willing to comply with study requirements i.e. provision of contact details and written, informed consent prior to enrolment
• Willing to provide sputa (expectorated or induced) for culture; and
• Meeting the definition for active TB.
• Contacts (cohort)
• ≥12 years old
• Meeting contact definition
• Able and willing to return for follow-up visits, with no plans to move soon
• Willing to comply with study requirements i.e. provision of contact details and written, informed consent or assent prior to enrolment
• Willing and able to provide sputum and blood
• Agree to potentially undergo CXR at M12 (women

You may not qualify if:

• Index cases
• No informed consent or assent
• More than six weeks has passed since the index case's first bacteriological result for TB was reported
• Patient was started on treatment based on empirical or clinical grounds (including CXR) alone
• Patient with rifampicin resistance (known from Xpert, Ultra, and/or MTBDRplus results)
• Contacts (cohort)
• No informed consent or assent
• Not diagnosed with active TB
• Unwilling or unable to provide blood
• More than six weeks has passed since reporting of the index case's first positive test result

Sponsors & Collaborators

• Amsterdam Institute for Global Health and Development: lead
• University of Stellenbosch: collaborator
• Makerere University: collaborator
• Centro de Investigacao em Saude de Manhica: collaborator
• Barcelona Institute for Global Health: collaborator
• Foundation for Innovative New Diagnostics, Switzerland: collaborator

Study Sites (3)

Centro de Invesigação em Saúde de Manhiça

Manhiça, Mozambique

Location

University of Stellenbosch

Cape Town, South Africa

Location

Makerere University

Kampala, Uganda

Location

Related Links

• project website

Biospecimen

Retention: SAMPLES WITH DNA

Fingerprick blood for point-of-care testing, two serum tubes, one Tempus RNA tube, urine (30ml) and sputum (max 3 sputa) will be collected from cohort participants who are TB presumptive or meeting sputum expectorator definition.

MeSH Terms

Conditions

Tuberculosis

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Grant Theron, PhD

  University of Stellenbosch

  PRINCIPAL INVESTIGATOR

• Alberto L Garcia-Basteiro, PhD

  Barcelona Institute for Global Health

  STUDY DIRECTOR

• Adam Penn-Nicholson, PhD

  The Foundation for Innovative New Diagnostics

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 12 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2021
• First Posted: April 1, 2021
• Study Start: April 21, 2021
• Primary Completion: January 31, 2025
• Study Completion: January 31, 2025
• Last Updated: February 5, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: The data will be available once the findings are published.
• Access Criteria: Data access will be granted to interested collaborators and parties through sharing of data files or login information for the study's secure RedCap electronic database during the course of patient recruitment.

Locations

UG (1); ZA (1); MO (1)