Dear Colleague Letters
New England Journal of Medicine: TB Trial Identifies Shorter Four-Month Treatment Regimen
May 10, 2021
The U.S. Centers for Disease Control and Prevention (CDC) Tuberculosis Trials Consortium (TBTC), together with collaborators from the National Institutes of Health’s (NIH) AIDS Clinical Trial Group (ACTG), is pleased to announce the publication of “Four-Month Rifapentine Regimens with or without Moxifloxacin for Tuberculosisexternal icon” in the New England Journal of Medicine. The article is accompanied by a supplementpdf iconexternal icon, editorialexternal icon, videoexternal icon and Research Summarypdf iconexternal icon.
Public health organizations around the world have been eagerly anticipating results of this trial. Shortening the time needed to cure TB from 6 months to 4 months will greatly benefit patients with TB disease, their families, and programs.
The article details findings from study 31/A5349 – an international, randomized, controlled, open label, phase 3 non-inferiority clinical trial. The trial demonstrated that a shorter four-month daily treatment regimen with high-dose (“optimized”) rifapentine and moxifloxacin is as effective as (non-inferior to) the standard daily six-month regimen in curing drug-susceptible tuberculosis (TB) disease. This important study was presented during the virtual 51st Union World Conference on Lung Health.
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.
- The successful four-month regimen – 2PHZM/2PHM – included eight weeks of daily treatment with rifapentine (P), isoniazid (H), pyrazinamide (Z), and moxifloxacin (M) and nine weeks of daily treatment with rifapentine (P), isoniazid (H), and moxifloxacin (M). At the conclusion of the trial, the four-month regimen met non-inferiority criteria for efficacy in all analyses and was safe and well-tolerated.
- A second four-month regimen – 2PHZE/2PH – included eight weeks of daily treatment with rifapentine (P), isoniazid (H), pyrazinamide (Z), and ethambutol (E) and nine weeks of daily treatment with rifapentine (P) and isoniazid (H). This new regimen did not meet non-inferiority criteria when compared to the existing standard regimen.
- The existing six-month regimen –2RHZE/4RH – includes eight weeks of daily treatment with rifampin (R), isoniazid (H), pyrazinamide (Z), and ethambutol (E) and approximately 18 weeks of daily treatment with rifampin (R) and isoniazid (H).
This is the first successful short treatment regimen for drug-susceptible TB disease identified in almost 40 years. The availability of shorter regimens enables patients to be cured faster, and has the potential to reduce treatment costs, improve patient quality of life, and increase completion of therapy.
CDC will use the results of this study to help inform future TB disease treatment guidelines, innovations for designing future clinical trials, and our work with TB programs and clinicians to improve available treatment regimens for TB disease.
Study 31/A5349 is the largest drug-susceptible TB disease treatment trial that CDC has ever sponsored, with more than 2,500 participants enrolled at 34 clinical sites in 13 countries. The participants were diverse and included important groups, such as adolescents, people living with HIV, and people living with diabetes. I would like to thank the researchers, clinical staff, and most of all, study participants, for their important and groundbreaking contributions that will bring us closer to our goal of TB elimination.
Philip LoBue, MD, FACP, FCCP
Division of Tuberculosis Elimination
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention