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Phase II-III clinical research
TB PRACTECAL is a multi-centre, multi-arm, open label, randomised, controlled, phase II-III trial to identify a shortened, safe, effective and tolerable new treatment regimen for adults with pulmonary multidrug-resistant and extensively drug-resistant tuberculosis (M/XDR-TB).
Breaking new ground
Designed to maximise the possibility of finding patient centred treatments and to speed progress, we intend to:
- Combine two new and highly promising anti-TB drug classes, diarylquinolines and nitroimidazoles, increasing the potential to radically improve treatment
- Target both MDR-TB and XDR-TB to tackle the spectrum of drug-resistant strains
- Identify a six-month regimen to dramatically reduce treatment time
- Utilise a pragmatic and adaptive trial design to speed progress and ensure that a new regimen is relevant for the people who need it most
Stage one of the study is identifying regimens that contain the new drugs bedaquiline and pretomanid for further evaluation based on safety and efficacy outcomes after eight weeks of treatment.
This will lead seamlessly to stage two of the study, which will evaluate the safety and efficacy of the best performing new regimens, at 72 weeks, compared with the World Health Organisation recommended standard of care used locally.
Outcomes will be measured against the current World Health Organisation recommended standard of care for DR-TB, which makes up the control arm of the trial.
Patient needs and safety lie at the heart of TB PRACTECAL, in full accordance with the Declaration of Helsinki and international standards for good clinical practice.
The new regimens in the study are designed to respond first and foremost to the needs of people with DR-TB – with few pills (no injections), taken orally, for six-months.
It is hoped that patients will experience fewer side effects so that they can comfortably complete their treatment at home.
Further, the regimens should be safe and effective for people living with HIV and co-infected with DR-TB, who are particularly vulnerable.
If successful, a new treatment of this kind could enable low and middle-income countries most affected by the DR-TB epidemic to dramatically increase treatment services. And with treatment still the best form of prevention, this could help to turn the global DR-TB crisis around.
New regimens meet criteria for Principles For Designing Future Regimens For MDR-TB: (i) containing at least one new class of drug; (ii) being broadly applicable for use against MDR and XDR-TB strains; (iii) containing three to five effective drugs, each from a different drug class; (iv) having an exclusively oral delivery; (v) having a simple dosing schedule; (vi) having a good side-effect profile that allows limited monitoring; (vii) having a maximum duration of six months; and (viii) having minimal interaction with antiretroviral drugs.
Published 25 October 2013, Principles For Designing Future Regimens For MDR-TB
The study incorporates an important community engagement component, with an overarching strategy and country-level plans adapted to each context for optimal relevance.
At its core is the ‘commitment to create a beneficial, respectful, sustained and transparent partnership that addresses the interests of all stakeholders in the research project, while supporting its ethical and scientifically rigorous conduct’.
To this end, TB PRACTECAL aims to:
- Engage in a two-way dialogue with community stakeholders, sharing knowledge and insights – in order to establish open communications, address local interests, develop mutual understanding and optimise the beneficence and relevance of the research.
- Develop a foundation of understanding and sensitise community stakeholders about research – in order to build on the capacity, knowledge and skills of people to actively engage in an effective partnership role, in support of the study’s ethical and scientifically rigorous conduct.
- Ensure community stakeholders are adequately informed and empowered throughout the research – in order to foster a transparent, respectful and constructive collaboration towards the successful implementation of the study.
As with all clinical trials, there are potential risks associated with using new therapies administered in new combinations.
These risks will be mitigated through a two-stage trial design with a long post-treatment follow-up period and a robust safety surveillance framework to ensure that people are not exposed to undue risk.
The trial is overseen by a Data and Safety Monitoring Board, part of a strong governance structure, to ensure that the highest patient safety, scientific and ethical standards are met throughout.