Prognostic Value of Interferon Gamma Release Assays in Predicting Active Tuberculosis Among Individuals With, or at Risk of, Latent Tuberculosis Infection
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Public Health England
- Enrollment
- 10,000
- Locations
- 3
- Primary Endpoint
- Development of active TB. Prognostic values of tests quantified as incidence rate ratios (RR) among contacts and new entrants
Study Overview
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.
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:
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 16 Years to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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
Outcomes
Primary Outcomes
Development of active TB. Prognostic values of tests quantified as incidence rate ratios (RR) among contacts and new entrants
Time Frame: two years
Secondary Outcomes
- Side effects from chemoprophylaxis(two years)