Determining the best treatment regimens for patients with MDR-TB
Globally, treatment success for multidrug-resistant tuberculosis (MDR-TB) is only 55 percent. Standard treatment is long, expensive, often ineffective and can require more than 14,000 pills, plus daily injections for six months or more. Side effects often include hearing loss, depression or psychosis, and kidney impairment.
The endTB project is providing data on improved MDR-TB treatment regimens that feature the two most recent anti-TB medicines, delamanid and bedaquiline, through an observational study in 17 countries and clinical trials. The project is also working to remove policy and market barriers that limit the new drugs’ widespread availability and use.
The project’s original term was 2015-2019 and its budget US$ 60 million, but with the extension, approved in September, 2018, it will run through the end of 2022, with Unitaid support of up to US$ 81 million.
The US$ 21 million extension includes a new clinical trial, known as the endTB-Q trial, to develop a treatment regimen for patients with extensively drug-resistant TB (XDR-TB) and pre-XDR-TB. Those patients have a type of MDR-TB that is resistant to fluoroquinolone.
The newly approved endTB-Q clinical trial will start enrollments in 2019 and is designed to use the same trial sites as the ongoing endTB trial, (Peru, Lesotho, Kazakhstan and South Africa), with new sites in India and Pakistan. The results of both clinical trials are expected in 2022.
Progress so far
As of December 2018, the endTB project observational study had enrolled more than 2,700 patients across the 17 endTB countries. Bedaquiline is available in all 17, and delamanid in 15 of the project countries as part of routine programmatic management of MDR-TB. Significant work has been carried out by consortium members to promote adoption of the principles of patient management with new TB drugs into national guidelines of the project countries. Members are also working to share the knowledge and data emerging from the project to support the use of new TB drugs on a global level. Specifically, interim analysis and data from the project have been shared and evaluated by WHO to inform the revision of the global MDR-TB treatment guidelines.
The ongoing endTB clinical trial for the new drugs is a randomized clinical trial that compares five experimental 9-month, injectable-free MDR-TB regimens to the WHO-approved longer MDR-TB regimen. The trial began enrollment in February 2017 in Georgia and is enrolling patients in four additional countries: Peru, Lesotho, Kazakhstan and South Africa. More than 190 patients were enrolled as of December 2018, with a study size of 750 patients.