Research to Improve the Detection and Treatment of Latent Tuberculosis Infection (RID-TB)

Aims and objectives: We will identify the factors influencing uptake of latent TB infection (LTBI) testing and completion of treatment among migrants entering the UK, develop materials to communicate and support LTBI testing and treatment interventions, evaluate the effectiveness and cost-effectiveness of a new Mycobacterium tuberculosis RD1-specific C-Tb skin test compared to interferon-gamma release-assay (IGRA) and assess the effectiveness and cost-effectiveness of a 12-dose rifapentine-based regimen with and without adherence support compared to current standard of care. Background: Following declines in the incidence of tuberculosis (TB) during the 20th century, there was a resurgence of the disease in England from the late 1980s to 2005. Consequently, NHS England and Public Health England (PHE) launched a strategy in 2015 to bring about a sustained decline with screening for latent TB infection (LTBI) as a funded element of the plan. LTBI testing and treatment reduces tuberculosis incidence by preventing reactivation, and is expected to create a cost saving to the NHS after about five years (NHS England). However, high rates of testing, treatment uptake and treatment completion are essential prerequisites to accrue these benefits. Research plan: In this 5-year programme of research, we have designed studies to improve access to diagnosis and enhance treatment uptake and completion in individuals with or at risk of LTBI. Through four interrelated workpackages conducted in parallel, we will combine a behavioural science theory-based approach together with clinical trials, health economics and modelling to assess interventions designed to support uptake of testing and treatment, and treatment completion. Studies will be conducted in high-volume primary and secondary care settings that are part of the LTBI screening programme in London. Workpackage 1 focuses on diagnostics. Study 1 will assess the diagnostic performance (concordance, sensitivity, specificity and predictive values) of the C-Tb test against the IGRA (the current standard of care). A minimum of 692 IGRA-tested individuals are required to provide 90% power to demonstrate C-Tb sensitivity and specificity against IGRA to within 5% of 94% accuracy. Study 2 will be a pragmatic randomised controlled trial (RCT) to assess C-Tb use within the NHS. Impact will be measured by comparing the proportion of patients who begin LTBI treatment after a positive C-Tb result to the proportion starting treatment after a positive IGRA. 400 individuals per arm are required in Study 2 to demonstrate non-inferiority of tests with 90% power, at 10% delta, assuming 60% attendance for treatment per arm and 5% one-sided alpha. Workpackage 2 will focus on behavioural science using mixed-methods. This will include qualitative work exploring people s experiences of LTBI testing (workpackage 1) and treatment (workpackage 3), including reasons for declining either or both of these, and quantitative assessments using validated measures of beliefs around illness and treatment. Through a process of co-creation, we will iteratively develop educational materials aimed at identified perceptual barriers to uptake and completion of testing and treatment. Workpackage 3 will address adherence and treatment completion. In a pragmatic, four-arm RCT, we will trial two interventions, alone and in combination, in comparison to standard care: a novel 12-dose weekly rifapentine/isoniazid LTBI treatment regimen vs. the standard daily rifampicin/isoniazid for 12 weeks, both with and without a novel adherence support intervention. 600 individuals will enable detection of an increase of at least 20% in any of the intervention arms (pairwise comparisons) with 90% power, assuming 5% significance 2-sided. Adherence support will comprise an electronic medication monitor reminder box (which also measures adherence) and educational materials developed in Workpackage 2 (see above). Workpackage 4 w