Study title: Optimal Treatment Duration of Radiographically Apparent, Bacteriologically Unconfirmed TB Identified Through Active Case Finding
Sponsor: University College London
Funders
Wellcome Trust, Medical Research Council Clinical Trials Unit at UCL
Lead researchers
Dr Mbusi Falayi, Professor Katharina Kranzer, Dr Edson Marambire
Partners
National University of Medical Sciences, Rawalpindi, Pakistan, The Aurum Institute, Johannesburg, South Africa, Clinical HIV Research Unit, Wits Health Consortium, Johannesburg, South Africa, Bulawayo City Health Department, Ministry of Health and Child Care, National TB Program, Zimbabwe
Background: TB remains the world’s leading infectious cause of death. Chest X-ray (CXR) screening is increasingly used in high TB-burden settings to detect asymptomatic or minimally symptomatic individuals. Many such individuals have radiographic signs consistent with TB but either test negative on sputum tests or cannot provide a specimen. These cases are termed "bacteriologically unconfirmed TB," and optimal treatment for them is unclear.
Clinical practice varies from immediate full-course treatment to deferring treatment until disease progresses. The RADIO-TB trial aims to determine whether shorter treatment durations are non-inferior to the standard 6-month course, thereby potentially minimizing toxicity and improving adherence. It also investigates whether immediate treatment is superior to deferred care.
Study Design
Phase 3, pragmatic, open-label, randomized controlled trial with six treatment arms using a response-over-continuous-intervention (ROCI) framework. Targeting to recruit 784 participants across 3 countries (approx. 198 in Zimbabwe), who are ≥16 years with CXR changes suggestive of TB, unable to produce sputum or with negative Molecular WHO-recommended rapid diagnostic tests (mWRD), no history of previous TB, and no alternative diagnosis.
Arm A (control arm): Standard 6-month treatment (2HRZE/4HR)
Arm B: 5-month TB treatment (2HRZE/3HR)
Arm C: 4-months TB treatment (2HRZE/2HR)
Arm D: 3-months TB treatment (2HRZE/1HR)
Arm E: 2-months TB treatment (2HRZE)
· Arm F: Deferred treatment. Close monitoring, with standard 6-month treatment initiated only upon progression or bacteriological confirmation
Start Date
April 2026