Project: Using Biomarkers to Predict TB Treatment Duration

Acronym	Predict TB (Reference Number: SRIA2015-1065)
Duration	01/02/2017 - 31/01/2022
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 which, although inferior to 24-week outcomes, suggests that a significant majority of patients are cured within 16 weeks. If those who are cured at 16 weeks could to be identified, treatment shortening could be successfully accomplished with this subset even with present drugs. Current biomarkers to predict treatment outcome are insufficient but important clues have emerged from previous studies that point towards extent of disease and bacterial burden as important contributors to poor treatment outcome. We have developed new early treatment stopping criteria that include PET/CT and GeneXpert cycle threshold. Hypothesis: A combination of microbiological and radiographic biomarkers will identify TB patients who are cured with 16 weeks of conventional therapy. Primary Objective To demonstrate that the 72-week (18-month) treatment success rate of standard treatment stopped early at week 16 is not inferior to treatment stopped at week 24, in subjects classified as low risk by PET/CT and bacterial load markers. Secondary Objectives 1) To evaluate the association of demographic, radiographic, bacterial load, microbiologic, and immunologic markers for predicting poor treatment outcome in the following cohorts: - Pooling high and low risk arms receiving the same duration of therapy, to evaluate the risk criteria. - Between low risk arms with shortened and standard treatment to evaluate any covariates, which predict greater rates of poor outcomes under treatment shortening. 2) To store biological samples for future biomarker research. 3) Develop a point-of-care lateral flow device to measure immunological markers as additional or replacement stopping criteria. This is a prospective, randomized, noninferiority phase 2b clinical trial of approximately 516 pulmonary drug sensitive TB subjects on HRZE for 8 weeks, followed by discontinuation of PZA and ethambutol. Those who meet early treatment completion criteria will be randomized at Week 16 either to continue therapy for the standard duration or to complete early at week 16, whereas failure to meet early completion criteria will continue on the standard regimen. All subjects will be followed until 72 weeks with the primary endpoint evaluated at 18 months. Capacity development and networking activities will be built around the clinical trial.
Network	EDCTP2
Call	Research & Innovation Action: Strategic Actions supporting large scale clinical trials

Project partner

Number	Name	Role	Country
1	Stellenbosch University	Coordinator	South Africa
2	ACADEMIC HOSPITAL LEIDEN	Partner	Netherlands
3	European Research and Project Office GmbH	Partner	Germany
4	Imperial College of Science Technology and Medicine	Partner	United Kingdom
5	LINQ Management GmbH	Partner	Germany
6	TASK Foundation NPC	Partner	South Africa
7	Universitaet Zuerich	Partner	Switzerland
8	University of Cape Town	Partner	South Africa
9	University of Cape Town Lung Institute (Pty) Ltd	Partner	South Africa