Current Organisation

The University of Cape Town Lung Institute (Pty) Ltd

Current Job Title

Head of Clinical Trials Unit – Pulmonologist

Biography

Project Title

Biomarker profile predicting unsuccessful treatment reponse in patients with MDR-TB

EDCTP Project Call

Career Development Fellowship (CDF)

Host Organisation

Project Objectives

To develop and validate an appropriately weighted dynamic clinical prediction rule which can predict unfavourable from favourable outcome in the treatment of MDR-TB. Furthermore such a rule would assist the TB clinician to intervene earlier in a patient who is likely to have unfavourable outcome as opposed to current standards that uses sputum culture, a process which delays such critical decisions by months.

Study Design

The proposed project was nested within the NexT RCT, a randomised control trial that is evaluating a new 6-month injection-free regimen for MDR-TB. This is a South African MRC-funded study which will recruit 300 patients with MDR-TB randomised to a WHO approved or intervention regimen. All the data and clinical samples required for the project were bio banked.

Project Summary

The emergence of MDR-TB in Africa is a serious public health concern. It is extremely expensive to treat and has high associated mortality, with rates of MDR-TB increasing in countries like South Africa, (32,000 MDR-TB cases were diagnosed last year), the situation is becoming unsustainable with a potential to destabilise TB programmes in Africa. The introduction of newer agents such as Bedaquiline and linezolid have renewed hope in the treatment of DRTB. However, clinical trials of new treatments for MDR-TB are expensive and prolonged, which delays registration and access to the drug. One of the major challenges in trials of new treatments for MDR-TB is the lack of tools to predict outcome. There are no validated biomarker profiles that will identify patients who are likely to have a favourable versus unfavourable outcome. If such a tool was available then reduced follow-up times would result in shorter studies. Phase II studies could be conducted to identify the most promising candidate regimens that could then move on to phase III trials in shorter time there by saving cost. Several trials are currently planned for testing various regimens for the treatment of MDR-TB and with Bedaquiline treatment failures starting to emerge the need for new drugs will likely increase over time. This proposal is to develop and validate an appropriately weighted dynamic clinical prediction rule which can predict unfavourable from favourable outcome in the treatment of MDR-TB. Furthermore such a rule would assist the TB clinician to intervene earlier in a patient who is likely to have unfavourable outcome as opposed to current standards that uses sputum culture, a process which delays such critical decisions by months. The proposed project will be nested with in the NexT RCT, a randomised control trial that is evaluating a new 6-month injection-free regimen for MDR-TB. This is a South African MRC-funded study which will recruit 300 patients with MDR-TB randomised to a WHO approved or intervention regimen. Thus all the data and clinical samples required for my project is currently being bio banked. The goal of the proposed project is to evaluate a package of treatment response biomarkers for MDR-TB with in the NExT RCT in order to formulate a weighted prediction rule incorporating clinical, radiological, mycobacterial, serum and urine biomarkers, which can predict unfavourable from favourable outcomes