The REMoxTB trial has found that replacing one of the drugs in the standard six-month treatment regimen with the antibiotic moxifloxacin did not allow the treatment time for tuberculosis (TB) patients to be shortened to four months. The results were presented at the 54th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) and published in the New England Journal of Medicine on 7 September.
TB is a major global health problem. Nearly 9 million people are diagnosed with the disease each year, and it killed 1.3 million people in 2012. The current treatment for TB requires patients to take tablets for 6 months. This makes it difficult for many patients to complete therapy, which has led to the emergence of multi-drug resistant TB (MDR-TB).
“Shorter and simpler TB cures are urgently needed—the present first-line treatment is nearly 50 years old, too complicated and interacts with common HIV medications,” said Mel Spigelman, MD, President and CEO of TB Alliance, the sponsor of the trial.
REMoxTB was a three-arm study that substituted moxifloxacin for either isoniazid or ethambutol in the first-line treatment for drug-sensitive TB (first-line treatment consists of isoniazid, rifampicin, pyrazinamide, and ethambutol).
The study found that, while the experimental regimens initially killed more TB bacteria than the standard regimen, patients receiving those shortened regimens were more likely to relapse than those taking the standard treatment. The researchers concluded that the four-month regimen could not be recommended.
The REMoxTB study was a collaboration between the TB Alliance, Bayer HealthCare AG, the University College London (UCL) Centre for Clinical Microbiology, the Medical Research Council Clinical Trials Unit at UCL and the University of St. Andrews. It enrolled 1,931 patients at 50 sites in nine countries (Kenya, Mexico, Tanzania, South Africa, China, India, Thailand, Malaysia and Zambia).
“We now know that substituting moxifloxacin for one drug in the current first-line treatment did not allow us to shorten treatment to 4 months,” said Stephen Gillespie, the Sir James Black Chair of Medicine at the University of St. Andrews and the trial’s chief investigator.
“The REMox trial was among the most rigorous TB drug trials ever conducted in the modern era of TB treatment and among the largest ever conducted for a new TB treatment. This has helped develop new research sites in developing countries that can conduct high quality research in the future to evaluate new regimens,” said Gillespie. “The quality and amount of the data from this trial will advance the entire TB research field, and improve future trials by allowing them to enroll fewer patients, making them shorter and less expensive to conduct.”
“This study has been critical in improving our understanding of how to analyse and interpret the results of trials aimed at shortening treatment for TB”, said Andrew Nunn, Professor of Epidemiology and Medical Statistics at the Medical Research Council Clinical Trials Unit at UCL.
The trial was funded by the Australian Department of Foreign Affairs (DFAT), Bill & Melinda Gates Foundation (BMGF), the Directorate General for International Cooperation of the Netherlands (DGIS), the European and Developing Countries Clinical Trials Partnership (EDCTP), Irish Aid, the UK Department for International Development (DFID), the US Agency for International Development (USAID), and the US National Institutes of Health AIDS Clinical Trial Group (ACTG).