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

September 29, 2020 updated by: Public Health England

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.

Study Overview

Status

Completed

Conditions

Detailed Description

DESIGN: Prospective cohort study of individuals (> or = 16 yrs) who are: (a) close contacts of TB cases or (b) new entrants from high incidence countries (>40/100000). SETTING: London TB clinics. NE London TB Network Primary Care Practices. All study sites will be coordinated from the HPA Centre for Infections.

HEALTH TECHNOLOGIES (LTBI MEASURES):Participants will be tested by Mantoux TST and two IGRA tests(Quantiferon-Gold In Tube ELISA) and ELISpot assay (same as Tspot.TB). A 25ml blood specimen will be collected with the residuum, after IGRA testing, full blood count and repetition of indeterminate assays, being stored for future research.

All tests will be conducted using standardised protocols.(6) ACTION AFTER TESTING: This will follow existing NICE guidance. (1;2) A) If negative by TST and IGRA, follow up only. B) If positive by either TST or IGRA tests, active TB will be excluded. Those without active TB will be followed up. C) If positive by IGRA & TST test and > 35 yrs, follow up only and for those 16-34 yrs, chemoprophylaxis will be offered with balanced advice about potential benefits/risks.

PRIMARY OUTCOME: Development of active TB. Prognostic values of tests quantified as incidence rate ratios (RR) among contacts and new entrants. SECONDARY OUTCOME: Side effects from chemoprophylaxis.

FOLLOW UP: average of 24 months from the date of IGRA/TST testing. a) phone call to GP and or patients at 24 months. b) national enhanced TB surveillance. c) national database of culture proven TB. d) Clinic records. ADDITIONAL DATA:

collected on all potential source cases and contacts using a questionnaire and medical records review (see below). HIV status will be determined at the end of the follow-up period through anonymised record linkage with the national HIV surveillance system, which is reliable.(4) DNA finger printing data, from the national strain typing database, will be utilised to ascertain transmission between index cases and subsequent diagnoses among contacts.

ANALYSIS PLAN: The predictive performance of each test (TST, ELISpot and ELISA) will be summarised as the RR of test positives in those developing active TB compared to not (analogous to positive likelihood ratio: TPR/FPR). GEE Poisson regression will compare disease RRs between tests accounting for length of follow-up and exploiting within patient comparisons of tests. Absolute risk of disease in different groups will be described in those with no evidence of LTBI and those with LTBI who have / have not received chemoprophylaxis. Other analyses: HIV infected and risk factors for LTBI.

SAMPLE SIZE: Assuming a LTBI rate of 30%, 5% progressing to active TB in 2 years if untreated and 20% loss to follow-up, simulations indicate a cohort of 5,000 would have 80% power of detecting clinically important differences in predictive performance (P<0.05) that would arise from differences in sensitivity and specificity of 10% between tests for detecting LTBI. 50% of TB contacts and new entrants are aged >35yrs, so a cohort of 10,000 identifies 5,000 for the primary analysis of progression without treatment. Testing and follow-up of 10,000 would allow appropriately powered secondary analyses a) comparing contacts and immigrants, b) estimating progression on treatment using regression models to adjust for test dependent treatment decisions.

ECONOMIC ANALYSIS: The cost-effectiveness of alternative screening strategies for patients with suspected LTBI will be assessed. A decision model will be developed to estimate the costs (£) and health effects (QALYs) of the following strategies: a) no screening, b) TST alone, c) different IGRA tests (ELISA or ELISpot), and d) TST followed by IGRA if positive. These strategies will be compared for: contacts and new entrants stratified by age and baseline risk. The model will use data from the cohort study and the published literature, and will follow the NICE reference case (5). Probabilistic sensitivity analysis will be used to assess uncertainty. Benefits due to prevention of transmission will be estimated.

Study Type

Observational

Enrollment (Actual)

10000

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • London, United Kingdom, E9 6SR
        • Homerton Hospital
    • London
      • Southall, London, United Kingdom, UB1 3HW
        • Ealing Hospital
      • Tooting, London, United Kingdom, SW17 0QT
        • St George's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

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).

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Contacts
Contacts of active cases of tuberculosis
new entrants
new entrants from high incidence (>40/100000) countries.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Development of active TB. Prognostic values of tests quantified as incidence rate ratios (RR) among contacts and new entrants
Time Frame: two years
two years

Secondary Outcome Measures

Outcome Measure
Time Frame
Side effects from chemoprophylaxis
Time Frame: two years
two years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Public Health England

Collaborators

Imperial College London
University College, London
Queen Mary University of London
University of Birmingham
Brunel University

Investigators

  • Principal Investigator: Ajit Lalvani, MD, PhD, Imperial College London

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2010

Primary Completion (ACTUAL)

June 30, 2015

Study Completion (ACTUAL)

June 30, 2016

Study Registration Dates

First Submitted

July 12, 2010

First Submitted That Met QC Criteria

July 13, 2010

First Posted (ESTIMATE)

July 14, 2010

Study Record Updates

Last Update Posted (ACTUAL)

October 1, 2020

Last Update Submitted That Met QC Criteria

September 29, 2020

Last Verified

May 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PREDICT (CardioDx)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Latent Tuberculosis

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in India

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe