LONDON – A trial aiming to find a better treatment for multidrug-resistant tuberculosis (MDR-TB) has stopped enrolling patients early after its independent data safety and monitoring board indicated that the regimen being studied is superior to current care, and more patient data was extremely unlikely to change the trial’s outcome.
TB-PRACTECAL, a phase II/III clinical trial sponsored by Doctors Without Borders/Médecins Sans Frontières (MSF), tested a six-month regimen of bedaquiline, pretomanid, linezolid and moxifloxacin, against the locally accepted standard of care. At the time of the interim analysis 242 patients had been enrolled in seven trial sites across Belarus, South Africa and Uzbekistan.
MSF is now preparing a dataset to share with the World Health Organization (WHO) as soon as possible, and full results will be submitted to a peer-reviewed journal in the coming months. MSF believes these findings will have the potential to change clinical practice.
“This will be the first-ever multi-country, randomised, controlled clinical trial to report on the safety and efficacy of a six-month, all oral regimen for drug-resistant TB,” said Professor David Moore from the London School of Hygiene and Tropical Medicine and a member of the Trial Steering Committee. “The findings could transform the way we treat patients with drug-resistant forms of TB worldwide, who have been neglected for too long.”
465,000 people developed rifampicin-resistant TB in 2019 and 182,000 died. Treatment is long, only cures three out of every five patients, and despite changes in WHO guidance, often still includes painful injections and drugs which cause toxic side effects including deafness.
“Our hope is that rigorous data from TB-PRACTECAL will be reviewed by WHO urgently and allow for the recommendation of this six-month regimen, which should translate into countries incorporating it into national treatment programmes,” said Professor Nargiza Parpieva, Country Coordinating Principal Investigator in Uzbekistan. “This could not only ultimately save many thousands more lives, but also vastly improve quality of life for those undergoing treatment. Patients on the trial tell us they no longer need to put their life on hold just to get cured.”
Since the first patient was enrolled onto the TB-PRACTECAL trial in 2017, new treatments for MDR-TB have become available. But lengthy regimens that patients struggle to complete are still the reality in many of the countries in which MSF works. WHO’s current guidelines recommend treatment lasting nine to 20 months for patients with MDR-TB.
Earlier this month, the trial’s independent data safety and monitoring board recommended that randomisation of patients into TB-PRACTECAL be stopped, as more data was extremely unlikely to change the results of the trial. As a result, MSF has closed enrolment to new patients last week.
“My heartfelt thanks to all our partners and to all the staff who’ve been involved in this complex project overcoming significant obstacles,” said Dr Bern-Thomas Nyang’wa, Chief Investigator of the trial. “Most of all, I am grateful to the people suffering from TB who took a chance on us, so future TB patients might be able to have access to better care.”