RadioTB trial: Optimal management of radiographically apparent, bacteriologically negative TB identified through active case finding

Chest X-ray (CXR) screening using computer-aided detection (CAD) software is the optimal approach to identify those with undiagnosed tuberculosis (TB) in communities and is being rapidly scaled-up globally with millions screened each year. Approximately 5-7% of people without previous TB history have a CXR suggestive of TB but no bacteriological confirmation and are at high-risk of progressing to develop infectious TB (approximately 10%/year). The optimal diagnostic and treatment approach for this group is unclear due to insufficient evidence and in practice is highly variable. Frequently the opportunity for early intervention to prevent transmission and minimise lung damage is missed. Our overall goal is to provide strong evidence to guide policy for programmatic management and to advance understanding about this early TB state. We will undertake the first randomised clinical trial (RCT) in this population for over 30 years, using a pragmatic approach and innovative duration-response design to determine the shortest duration of the standard regimen required to prevent progression. The trial will be undertaken in South Africa, Zimbabwe and Pakistan alongside programmatic screening, providing efficiency. In addition, we will evaluate the potential of novel diagnostic approaches, model the impact on transmission, and evaluate the cost- effectiveness of the different management strategies.