Results from an international, randomized, controlled clinical trial indicate that a four-month daily treatment regimen containing high-dose, or “optimized,” rifapentine with moxifloxacin is as safe and effective as the existing standard six-month daily regimen at curing drug-susceptible tuberculosis (TB) disease.
Tuberculosis (TB) is a potentially serious infectious disease that mainly affects your lungs. The bacteria that cause tuberculosis are spread from one person to another through tiny droplets released into the air via coughs and sneezes.
Once rare in developed countries, tuberculosis infections began increasing in 1985, partly because of the emergence of HIV, the virus that causes AIDS. HIV weakens a person’s immune system so it can’t fight the TB germs. In the United States, because of stronger control programs, tuberculosis began to decrease again in 1993 but remains a concern.
Many strains of tuberculosis resist the drugs most used to treat the disease. People with active tuberculosis must take several types of medications for many months to eradicate the infection and prevent the development of antibiotic resistance.
This regimen is the first successful short-course treatment regimen for drug-susceptible TB disease in almost 40 years. TB is one of the most important global health problems. According to recent estimates from the World Health Organization, 10 million new TB cases and 1.4 million deaths from TB occurred globally in 2019. While the United States has achieved substantial progress in reducing TB, with fewer than 10,000 cases each year, too many people still suffer from TB disease.
The Phase 3, open-label trial, called Study 31/A5349, was led by the U.S. Centers for Disease Control and Prevention’s (CDC) Tuberculosis Trials Consortium (TBTC) with collaboration from the AIDS Clinical Trials Group (ACTG) funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. It is the largest drug-susceptible TB disease treatment trial that CDC or NIAID has ever conducted, with more than 2,500 participants ages 12 and older enrolled at 34 clinical sites in 13 countries. The trial included 214 people with HIV. Results were presented today at the virtual Union World Conference on Lung Health and have been submitted for publication.
Shortening treatment for TB disease can benefit patients, families, healthcare providers and health systems. Shorter TB disease treatment regimens can help patients more easily complete treatment for TB disease than they would on the existing standard regimen. This is especially important in the era of COVID-19, which has caused widespread disruptions to care and treatment access for many people with TB disease. The availability of shorter regimens enables patients to be cured faster, and has the potential to reduce treatment costs, improve patient quality of life, increase completion of therapy, and reduce development of drug resistance.
“The CDC’s TB Trials Consortium is a global leader in driving innovation and advances in TB treatment and prevention, such as this new four-month regimen,” said Philip LoBue, MD, FACP, FCCP, director of CDC’s Division of Tuberculosis Elimination. “These results help bring us closer to our goal of TB elimination, and we are grateful to the researchers, clinical staff, and most of all, study participants, for their important contributions.”
“These robust findings have the potential to change clinical practice by offering people with drug-susceptible TB an additional, shorter-course treatment option that is safe, effective and potentially more convenient,” said Carl W. Dieffenbach, Ph.D., director of the NIAID Division of AIDS. “The Study 31/A5349 trial was completed right on schedule, demonstrating the effectiveness of the collaboration between CDC and NIAID.”
Study 31/A5349 examined the efficacy and safety of two four-month regimens with high-dose rifapentine with or without moxifloxacin for the treatment of drug-susceptible TB disease. These were compared with the existing six-month regimen (2RHZE/4RH), which includes eight weeks of daily treatment with rifampin, isoniazid, pyrazinamide, and ethambutol and 18 weeks of daily treatment with rifampin and isoniazid.
One of the four-month regimens – 2PHZM/2PHM – included eight weeks of daily treatment with high-dose, or “optimized,” rifapentine, isoniazid, pyrazinamide, and moxifloxacin and nine weeks of daily treatment with rifapentine, isoniazid, and moxifloxacin. At the conclusion of the trial, the four-month regimen met non-inferiority criteria for efficacy in all of the several planned analyses and was safe and well-tolerated.
A second new treatment regimen used in this study – 2PHZE/2PH – included eight weeks of daily treatment with the same dose of rifapentine, isoniazid, pyrazinamide, and ethambutol and nine weeks of daily treatment with rifapentine and isoniazid. This new regimen did not meet non-inferiority criteria when compared to the existing standard regimen.
The safety profile for this trial demonstrates that the proportion of patients who experienced adverse events was similar among patients in all three groups of participants (control and the two novel regimen groups). This means that the novel regimens do not pose greater risk to patients than currently used regimens.
Study 31/A5349 will inform future TB treatment in the U.S. CDC and NIH will continue to work with TB control programs and clinicians to improve available treatment and prevention regimens for TB disease.
CDC’s Division of Tuberculosis Elimination Director, Philip LoBue, and NIAID’s Division of AIDS Director, Carl Dieffenbach, are available for comment on this study’s implications for the future of TB disease treatment.