Project: Evaluating the response to 4 and 6 month treatment of pulmonary tuberculosis by 18F-FDG PET/CT lung imaging

Acronym Evaluate 4mTB (Reference Number: TMA2016CDF-1576)
Duration 01/04/2018 - 31/03/2021
Project Topic Shortening of tuberculosis (TB) treatment to 16 weeks or shorter is a main priority of TB research to decrease cost, improve treatment adherence and decrease development of drug resistance. Clinical trials of treatment shortening have thus far all failed but have consistently found 80-85% treatment success rates in the 16-week arms. This suggests that the majority of patients are cured within 16 weeks. If they could to be identified, treatment shortening could be successfully accomplished in this subset. It also indicates a lack of understanding of biomarkers to monitor treatment response, which confounds the development of new approaches to treat pulmonary tuberculosis (PTB). Recently, 18F-Fluorodyoxyglucose Positron Emission TomographyComtputed tomography(PET/CT) have shown promise to be a useful tool to stratify risk, monitor response and provide insight into the dynamics of MTB versus host interaction during TB treatment. Evaluate 4mTB will form a substudy to the PredictTB trial. The parent study’s aim is to demonstrate that the 72- week (18-month) treatment success rate of standard treatment stopped after 16 weeks is not inferior to treatment stopped after 24 weeks, in subjects classified as low risk by a new criteria, based on PET/CT scans at baseline and week 4. Aim: Evaluate 4mTB will validate and optimise the functional and anatomical characteristics, previously identified by 18F-FDG PET/CT scans on patients with PTB ( with a focus on scans at 16 and 24 weeks), and use this information to provide insight into the dynamics of MTB versus host interaction, serve as a prognostic indicator and facilitate the discovery of biomarkers to monitor and understand treatment response during 16 and 24 week treatment courses. Methods: In this prospective, randomised, non-inferiority phase 2b trial, I will work as part of an international consortium. We will recruit and follow up 516 patients with PTB for 72 weeks, and perform PET/CT scans at Dx, 4 weeks and 16 weeks. Those that meet early treatment criteria, will be randomized to treatment of either 16 or 24 weeks. Expected impact: Scans at the end of treatment should be more accurate than early treatment scans, since more treatment response variables have taken effect and provide a better understanding of lung pathology after shortened treatment. This should facilitate the discovery of biomarkers to evaluate the end-of-treatment TB infection status in the lung, regardless of treatment duration. In turn, this would be a major step towards easy and affordable tests to allow individualised treatment duration. This fellowship will provide the opportunity for the Fellow to work with international experts, to gain experience and knowledge in scientific discovery, innovation, implementation and trial management, allowing him to realise his goal and become and independent investigator, to improve health solutions and drive development in Africa.
Network EDCTP2
Call Career Development Fellowships 2016

Project partner

Number Name Role Country
1 Stellenbosch University Coordinator South Africa