Landmark phase III trial shows that the shorter regimen containing rifapentine and moxifloxacin can safely and effectively cure TB in four months
Contact: Mike Frick, TB Project Co-Director (mike.frick@treatmentactiongroup.org)
EMBARGOED until Wednesday, October 21 at 10:00 a.m. EST.
October 21, 2020 –Treatment Action Group (TAG) and the Community Research Advisors Group (CRAG) welcome the news of a safe and effective regimen for shortening tuberculosis (TB) treatment to just four months. Reported today at the 51st Union World Conference on Lung Health, a landmark publicly-funded phase III clinical trial, conducted at 34 sites in 13 countries, found that this regimen containing rifapentine and moxifloxacin performed as well as the six-month standard regimen.
“We receive the results with a lot of gratification and happiness,” stated Dorothy Namutamba, CRAG co-chair. “TB-affected communities have always wished for shorter, easier TB treatment with fewer side effects. We strongly believe this is a real breakthrough, as the new regimen will generate better treatment outcomes for TB patients. We are on the path to wipe out TB as a killer disease.”
This scientific advance stands to benefit the millions of people who are affected by pulmonary TB worldwide each year. The six-month standard regimen for TB has been in place for decades. The long duration of treatment has posed a challenge for patients, practitioners, and programs, and helped contribute to the rise of drug resistance. Previous trials tested other fluoroquinolone-based, four-month treatment regimens, but none have succeeded until now. “Shorter treatment regimens will be easier for both patients and health care providers; more patients will complete therapy and be cured. This is a landmark event in our quest for even shorter treatments and should be implemented immediately,” explained Barbara Seaworth, co-chair of the CRAG.
The TBTC Study 31/ACTG A5349 trial was a collaboration between the U.S. Centers for Disease Control and Prevention (CDC) TB Trials Consortium (TBTC) and the U.S. National Institutes of Health (NIH) AIDS Clinical Trials Group (ACTG). This phase III clinical trial enrolled over 2,500 people with TB, making it the largest TB treatment trial in decades. The trial stands out for its inclusivity, enrolling a diverse population, including adolescents aged 12–17, people living with HIV with low CD4 cell counts, and people with cavitary TB (indicating more serious disease).
The trial also had a robust community engagement program. Cynthia Chirwa, CRAG member and community representative to the Study 31/A5349 protocol team, explains that “community engagement is a critical cornerstone of ethical research. The CRAG and Community Partners, a NIH community advisory mechanism, have been involved throughout the process to advance TB research ethically and safely. Researchers adapted the design of this study to meet the needs and requests of TB-affected communities in addition to answering valuable scientific questions.”
“We call for national TB programs, regulatory agencies, and international organizations to make this four-month regimen of existing drugs available as soon as possible—starting in the countries that hosted clinical trials sites that made this result possible,” said Mike Frick, TAG’s TB Project Co-Director. “Considering that this was a publicly funded study, the results should be considered as a public good made available to all. We further encourage funders and researchers to fill remaining data gaps so that this new, shorter regimen can be used in children under 12, in pregnant women, and in people with co-morbidities not included in Study 31/A5349.”
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About the Community Research Advisors Group (CRAG): The CRAG is an international, community-driven advisory body that works to ensure the meaningful representation and engagement of affected communities in research conducted by the Tuberculosis Trials Consortium (TBTC). This group of research-literate activists supports a robust, comprehensive, and innovative TBTC research agenda that is responsive to community needs and scientific priorities.
About TAG: Treatment Action Group (TAG) is an independent, activist and community-based research and policy think tank fighting for better treatment, prevention, a vaccine, and a cure for HIV, tuberculosis, and hepatitis C virus. We are science-based treatment activists working to expand and accelerate vital research and effective community engagement with research and policy institutions.
About TBTC Study 31/ACTG A5349:
Study 31/A5349 was a three-arm trial assessing if either of two novel 4-month treatment regimens was as effective as the standard daily 6-month treatment:
- One experimental regimen, the one shown as effective as the standard arm: 2 months of daily isoniazid, rifapentine, pyrazinamide, moxifloxacin, followed by 2 months of daily isoniazid, rifapentine, moxifloxacin.
- The other experimental regimen, the one not shown as effective as the standard: 2 months of daily isoniazid, rifapentine, pyrazinamide, ethambutol, followed by 2 months of daily isoniazid, rifapentine.
- Control arm, standard treatment regimen for drug-susceptible pulmonary TB: 2 months of daily isoniazid, rifampicin, pyrazinamide, ethambutol, followed by 4 months of daily isoniazid, rifampicin.
One of the two novel arms—the experimental regimen which replaced both rifampicin (with an optimal 1200 mg dose of rifapentine) and ethambutol (with a standard 400 mg dose of moxifloxacin)—was shown to be equally effective as the control arm and was safe and well tolerated. The other experimental arm (with rifapentine 1200 mg but no moxifloxacin) was not as effective overall. The study achieved high adherence to study medication with directly observed treatment (DOT) and high participant retention. The study was conducted in 13 countries: Brazil, Haiti, Hong Kong, India, Kenya, Malawi, Peru, South Africa, Thailand, Uganda, United States of America, Vietnam, Zimbabwe.