STREAM is being implemented as part of the TREAT TB project.

STREAM is the first large-scale, multi-country clinical trial to examine shortened regimens for MDR-TB. It is also the first phase III trial to test the efficacy and safety of bedaquiline in a shorter regimen. STREAM began in 2012 as an academic non-registration trial (Stage 1) funded by the United States Agency for International Development and the UK Department for International Development through a grant to the UK Medical Research Council Clinical Trials Unit at University College London (MRC CTU at UCL).

STREAM Stage 1 compared a 9–11-month MDR-TB regimen to the locally-used regimen in line with 2011 World Health Organization (WHO) guidance (approximately 20 months). Stage 2 (which added two bedaquiline-containing arms) resulted in additional funding from Janssen Pharmaceuticals and STREAM becoming a US Food and Drug Administration (FDA) regulated registration trial. The two stages of the trial recruited more than 1,000 participants at sites in Ethiopia, Georgia, India, Moldova, Mongolia, South Africa, Uganda, and Vietnam, making STREAM the world’s largest recruited clinical trial for MDR-TB.

Infographic of the STREAM Clinical Trial.

Results from Stage 1 were published in the New England Journal of Medicine and demonstrated that favorable outcomes for participants on the control (approximately 20 months) and intervention (9–11 months) regimens were very similar under trial conditions. The STREAM Stage 1 results, which also showed that the shorter regimen can reduce costs to the health system and patients, as published in the Bulletin of the World Health Organization, played a key role in the development of the WHO recommendations on the use of shorter regimens to treat MDR-TB.

STREAM Stage 2, which is ongoing, is evaluating an all oral, bedaquiline-containing regimen that is potentially as effective as and more tolerable than the injectable-containing regimens currently in use. It is also evaluating the comparative cost of the two regimens, for both the patient and the health system. Stage 2 is expected to contribute important evidence for future policy decisions about injectable-free MDR-TB regimens. Recruitment to Stage 2 of the trial was completed in January 2020 and results are expected in 2022.