Dear Colleague Letters
Landmark TB Trial Identifies Shorter-Course Treatment Regimen
October 21, 2020
On October 21, 2020 during the virtual 51st Union World Conference on Lung Health, the U.S. Centers for Disease Control and Prevention (CDC), Tuberculosis Trials Consortium (TBTC) with collaborators from the National Institutes of Health’s (NIH) AIDS Clinical Trial Group (ACTG), announced the results of Study 31/A5349. Study 31/A5349 – an international, randomized, controlled, open label, phase 3 non-inferiority clinical trial –identified a shorter four-month daily treatment regimen with high-dose, or “optimized,” rifapentine and moxifloxacin that is as effective as (non-inferior to) the standard daily six-month regimen in curing drug-susceptible tuberculosis (TB) disease. This is the first successful short treatment regimen for drug-susceptible TB disease identified in almost 40 years. These results can help inform future TB disease treatment.
Reducing the length of time for treating TB has been a longstanding public health goal. Shortening treatment for TB disease can benefit patients, families, TB programs and other healthcare providers, and health systems. 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.
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 and people living with HIV.
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 two months (eight weeks) of daily treatment with rifapentine (P), isoniazid (H), pyrazinamide (Z), and moxifloxacin (M) and 2 months (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 two months (eight weeks) of daily treatment with rifapentine (P), isoniazid (H), pyrazinamide (Z), and ethambutol (E) and two months (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 two months (eight weeks) of daily treatment with rifampin (R), isoniazid (H), pyrazinamide (Z), and ethambutol (E) and approximately four months (18 weeks) of daily treatment with rifampin (R) and isoniazid (H).
CDC will use the results of this study to help inform future TB disease treatment guidelines and innovations for designing future clinical trials. CDC will continue to work with TB control programs and clinicians to improve available treatment regimens for TB disease. The study also highlights the great power of collaboration; it would not have been completed so rapidly had it not been for the strong partnership between two leading U.S. health agencies, CDC and NIH.
These results help bring us closer to our goal of TB elimination. I am grateful to the researchers, clinical staff, and most of all, study participants, for their important contributions to this study.
Philip LoBue, MD, FACP, FCCP
Division of Tuberculosis Elimination
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention