Prognostic Value of Interferon Gamma Release Assays in Predicting Active Tuberculosis Among Individuals With, or at Risk of, Latent Tuberculosis Infection

NCT01162265 | Completed DMC

• 1 other identifier: PREDICT
• Study Type: observational
• Target: 10,000
• Locations: 1 country
• Sites: 3

Brief Summary

The objective of this study is to assess the efficacy of the two current TB (tuberculosis) blood tests (Interferon Gamma Release Assays (IGRA)) compared with the standard skin test (Mantoux Tuberculin Skin Test (TST)), for predicting active tuberculosis among those at increased risk of TB. Those at increased risk are defined as either newly arrived immigrants or people who have been in contact with TB cases. The study will also provide information on the cost effectiveness of different testing strategies, such as the two step testing approach recommended by NICE. The study is to be funded by the NIHR Health Technology Assessment programme. 10,000 participants will be recruited from 12 hospitals and a network of GP surgeries in London. All participants will have the skin test and blood taken for both assays. Disease status of participants will then be followed up for an average of 24 months using the national register of clinical reports, a phone call and the national microbiological database. The risk of developing active disease is highest in the first two years after exposure. During followup there will be no additional diagnostic procedures unless symptoms occur, i.e. in line with current NICE policy. A sub group of patients, selected as a random 25% of participants, will have a repeat IGRA test shortly after the first test to investigate whether the skin test affects the result of the blood test.

Conditions

Tuberculosis; Latent Tuberculosis

Keywords

Tuberculosis; IGRA; latent

Outcome Measures

Primary Outcomes (1)

• Development of active TB. Prognostic values of tests quantified as incidence rate ratios (RR) among contacts and new entrants

  two years

Secondary Outcomes (1)

• Side effects from chemoprophylaxis

  two years

Study Arms (2)

Contacts

Contacts of active cases of tuberculosis

new entrants

new entrants from high incidence (\>40/100000) countries.

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Those who are close contacts of active tuberculosis cases or those who have are new entrants to the UK from high incidence countries (\>40/100000).

You may qualify if:

• Contacts of all active TB (pulmonary and extrapulmonary) patients. (Contacts will include all individuals with a cumulative duration of exposure of greater than eight hours to the relevant index case in a confined space during the period of infectiousness (prior to initiation of treatment) who attend designated clinics.
• New entrants from high incidence countries (incidence of TB of \>40/100000) who attend designated clinics

You may not qualify if:

• Patients who are unable to give informed consent
• Children under 16 years of age
• Individuals found to have active TB at the time of screening

Sponsors & Collaborators

• Public Health England: lead
• Imperial College London: collaborator
• Queen Mary University of London: collaborator
• University College, London: collaborator
• Brunel University: collaborator
• University of Birmingham: collaborator

Study Sites (3)

Ealing Hospital

Southall, London, UB1 3HW, United Kingdom

Location

St George's Hospital

Tooting, London, SW17 0QT, United Kingdom

Location

Homerton Hospital

London, E9 6SR, United Kingdom

Location

Related Publications (5)

• Lule SA, Gupta RK, Krutikov M, Jackson C, Southern J, Abubakar I. The relationship between social risk factors and latent tuberculosis infection among individuals residing in England: a cross-sectional study. BMJ Glob Health. 2020 Dec;5(12):e003550. doi: 10.1136/bmjgh-2020-003550.

  PMID: 33293291 DERIVED

• Katelaris AL, Jackson C, Southern J, Gupta RK, Drobniewski F, Lalvani A, Lipman M, Mangtani P, Abubakar I. Effectiveness of BCG Vaccination Against Mycobacterium tuberculosis Infection in Adults: A Cross-sectional Analysis of a UK-Based Cohort. J Infect Dis. 2020 Jan 1;221(1):146-155. doi: 10.1093/infdis/jiz430.

  PMID: 31504674 DERIVED

• Abubakar I, Lalvani A, Southern J, Sitch A, Jackson C, Onyimadu O, Lipman M, Deeks JJ, Griffiths C, Bothamley G, Kon OM, Hayward A, Lord J, Drobniewski F. Two interferon gamma release assays for predicting active tuberculosis: the UK PREDICT TB prognostic test study. Health Technol Assess. 2018 Oct;22(56):1-96. doi: 10.3310/hta22560.

  PMID: 30334521 DERIVED

• Abubakar I, Drobniewski F, Southern J, Sitch AJ, Jackson C, Lipman M, Deeks JJ, Griffiths C, Bothamley G, Lynn W, Burgess H, Mann B, Imran A, Sridhar S, Tsou CY, Nikolayevskyy V, Rees-Roberts M, Whitworth H, Kon OM, Haldar P, Kunst H, Anderson S, Hayward A, Watson JM, Milburn H, Lalvani A; PREDICT Study Team. Prognostic value of interferon-gamma release assays and tuberculin skin test in predicting the development of active tuberculosis (UK PREDICT TB): a prospective cohort study. Lancet Infect Dis. 2018 Oct;18(10):1077-1087. doi: 10.1016/S1473-3099(18)30355-4. Epub 2018 Aug 30.

  PMID: 30174209 DERIVED

• Jackson C, Southern J, Lalvani A, Drobniewski F, Griffiths CJ, Lipman M, Bothamley GH, Deeks JJ, Imran A, Kon OM, Mpofu S, Nikolayevskyy V, Rees-Roberts M, Sitch A, Sridhar S, Tsou CY, Whitworth H, Abubakar I. Diabetes mellitus and latent tuberculosis infection: baseline analysis of a large UK cohort. Thorax. 2019 Jan;74(1):91-94. doi: 10.1136/thoraxjnl-2017-211124. Epub 2018 May 15.

  PMID: 29764958 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

A biobank will be established from samples collected in this study, subject to routine HTA requirements in the UK. This has full ethical approval and is included in the consent to take part in the study.

MeSH Terms

Conditions

Tuberculosis; Latent Tuberculosis

Condition Hierarchy (Ancestors)

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

Study Officials

• Ajit Lalvani, MD, PhD

  Imperial College London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2010
• First Posted: July 14, 2010
• Study Start: August 1, 2010
• Primary Completion: June 30, 2015
• Study Completion: June 30, 2016
• Last Updated: October 1, 2020

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (3)