Nurses prepare patients’ treatments in the pharmacy of the ambulatory ward at the National Centre for Tuberculosis and Lung Disease in Georgia’s capital, Tbilisi. (Daro Sulakauri/MSF)
Testing, novel, short, all-oral regimens for MDR-TB
Médecins Sans Frontières (MSF), Partners In Health (PIH) and its partners have launched a major clinical trial which seeks to revolutionize treatment for the toughest strains of tuberculosis (TB), the world’s leading infectious disease killer
Clinical trial activities across PIH and MSF will be linked via the endTB coordinating Principal Investigators, Drs. Carole Mitnick (Harvard Medical School and PIH) and Lorenzo Guglielmetti (MSF). The clinical trial is sponsored by MSF.
The clinical trial is expected to enroll 750 patients across six countries: Georgia, Kazakhstan (2 sites), Kyrgyzstan, Lesotho, Peru (2 sites) and South Africa. These are all countries with significant TB burdens, where MSF or PIH support local MDR-TB treatment activities.
The first patient started treatment in Georgia, in March 2017. As of July 2018, there are 131 patients enrolled in seven sites.
Why this clinical trial?
Current treatments for MDR-TB are long (up to 24 months), ineffective (only 54% succeed) and often cause terrible side effects, including acute psychosis and permanent deafness. All the while, patients endure months of painful, daily injections and ingest up to 14,000 pills. Moreover, the costliness, difficulty and length of current treatments make them hard to implement in many high-burden countries.
To address the problem, this phase III clinical trial uses the first TB drugs developed in almost 50 years — bedaquiline and delamanid — to find radically shorter (9 months), injection-free, more tolerable treatments for MDR-TB. (The new drugs will be combined into experimental new treatments with other oral TB drugs such as clofazimine, linezolid, fluoroquinolones and pyrazinamide.)
The central team
- Dr. Carole Mitnick (Harvard Medical School)
- Dr. Lorenzo Guglielmetti (Médecins sans Frontières)
Clinical trial (Output 2) Co-Investigators
- Elisabeth Baudin (Epicentre)
- Maryline Bonnet (Epicentre)
- Dr. Bouke de Jong (Antwerp Institute of Tropical Medicine)
- Dr. Michael Rich (Partners In Health)
- Dr. Alex Telnov (Médecins sans Frontières)
- Dr. Francis Varaine (Médecins sans Frontières)
- Dr. Gabriella Ferlazzo (Médecins sans Frontières)
- Dr. Gustavo Velásquez (Harvard Medical School)
This is a randomized, controlled, trial of five new, all, oral, 9-month regimens compared to the current standard of care. Randomization will be outcome adapted, rather than fixed. This means that the probability of being randomized to regimens changes as the outcomes are reported: more patients will be assigned to regimens that are producing better outcomes.
Study treatment regimens
Each experimental regimen will contain at least one new drug, in combination with up to four companion drugs. The control regimen will be composed according to local interpretation of WHO guidance and may include a new drug if indicated.
Several independent groups will provide formal external oversight of the study protocol, implementation, operation and analysis:
- Institutional Review Boards or Ethics Committees at Harvard Medical School, MSF, Antwerp Institute of Tropical Medicine and in each country participating in the clinical trial
- Independent Scientific Advisory Committee (SAC)
- Global Community Advisory Board, convened by the Treatment Action Group
- Data Safety and Monitoring Board (DSMB)
These groups will continue to assure the relevance of the trial for clinical care and policy, its safety for participants, and that global standards for clinical research are met or exceeded.