A first-ever clinical trial of a new, all-oral, treatment regime for multidrug-resistant tuberculosis (MDR-TB)  has stopped enrolling patients after initial data provided positive results that the new treatment could potentially save thousands of lives, as well as improving peoples’ quality of life.

Findings of the TB-PRACTECAL, Phase II/III clinical trial sponsored by Médecins Sans Frontières (MSF), were originally due to be reported in late 2021 or early 2022. 

But an independent data safety and monitoring board found that one of the regimens being studied in the trial – bedaquiline, pretomanid, linezolid and moxifloxacin –  has already shown itself to be superior to current care, which typically also involves the use of drug injections, since MDR TB is available to standard oral treatment formulations.  More patient data would be extremely unlikely to change the trial’s outcome, the safety board determined.

Findings Could Transform Treatment Of MDR-TB

MSF, in announcing the findings on Wednesday (World TB Day), said that it believes the regime could dramatically change clinical care standards, saying it would soon share the trial data with the World Health Organization (WHO), with full results being submitted to a peer reviewed journal in the coming months. 

“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.”

Treatment for MDR-TB is commonly administered for 2 years or longer and involves daily injections for six months, according to the TB Alliance. Many second-line drugs are toxic and have severe side effects. However, the complexity and prohibitive cost of MDR-TB treatment means that few of the world’s MDR-TB patients actually receive proper treatment.

Study Tested Six-Month Oral Combination Regime 

The multi-country, randomized controlled trial involved testing the 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 said that since the first patient enrollment in 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. The WHO’s current guidelines recommend treatment lasting nine to 20 months for patients with MDR-TB,” MSF said in its statement.

About one-quarter of the world’s population has a TB infection, with an estimated 10 million infections and 1.4 million TB deaths in 2019. Worldwide, TB is one of the top 10 causes of death and the leading cause from a single infectious agent (above HIV/AIDS). MDR-TB remains a public health crisis and a health security risk. Of the 465 people who developed rifampicin-resistant TB in 2019, 182, 000 died.

The current standard treatment for MDR-TB is arduous, lasting between nine to 24 months, exposes patients to serious side effects, and is only successful in about half of all cases. 

552 Patients Participated In Three Stages Of The TB-PRACTECAL Trial

Altogether some 552 MDR TB patients participated in three stages of the TB-PRACTECAL trial – a  multi-arm, multistage, open label, RCT which enrolled patients into three investigational regimens, comparing various combination treatments against the current standard of care. 

“Our hope is that rigorous data from TB-PRACTECAL will be reviewed by the 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.”

Image Credits: msf.