The ACTG is pleased to share the primary results of Study 31/A5349, which were presented at the 51st virtual Union World Conference on Lung Health on October 21st, 2020. This important study showed that the four-month regimen of rifapentine, isoniazid, pyrazinamide, and moxifloxacin (RPT-MOX) was non-inferior to the currently recommended six-month regimen of rifampicin, isoniazid, ethambutol, and pyrazinamide for the treatment of drug-susceptible pulmonary TB. RPT-MOX was also safe and well-tolerated by patients. A second four-month regimen of rifapentine, isoniazid, pyrazinamide, and ethambutol failed to meet the non-inferiority margin.
To put this study in historical context, the last time pulmonary TB treatment was successfully shortened for drug-susceptible TB was 48 years ago, when the British Medical Research Council (MRC) published results showing a six-month regimen was as effective as the standard 18-month regimen at that time. Despite many trial attempts to shorten TB therapy since, the standard treatment regimen for drug-susceptible pulmonary TB has remained at six months.
Thirteen countries contributed to Study 31/A5349, a phase 3, open-label, randomized controlled clinical trial, at 34 clinical sites. Approximately 2,500 people aged 12 years and older participated in the study, including 214 people with HIV infection. The study was led by the CDC Tuberculosis Trials Consortium (TBTC) in collaboration with the ACTG. ACTG sites enrolled two-thirds of participants and TBTC sites enrolled one-third.
Participants with HIV infection were enrolled in a staged fashion to allow for drug-drug interaction studies between rifapentine and efavirenz, which is why the number was relatively small. Reassuringly though, the participants did just as well as those without HIV, and the RPT-MOX regimen was also non-inferior and safe in these participants.
“Shortening treatment for TB has been front and center in the TB TSG scientific agenda for decades, and this new regimen that reduces treatment by two months will facilitate significant progress in global tuberculosis control,” said Dr. Susan Swindells of the University of Nebraska Medical Center and a co-chair of the study.
“This trial demonstrates the value of collaborative efforts between the ACTG and other networks,” added Dr. Richard Chaisson of Johns Hopkins University, another co-chair of the trial.
Shortening TB treatment to four months instead of six represents a major advancement in the management of this age-old infectious disease. Congratulations to the study team and participating sites for this astounding achievement!