STREAM is the first large-scale, multi-country clinical trial to examine shortened treatment regimens for multidrug-resistant tuberculosis (MDR-TB). It is also the first phase III trial to test the effectiveness and safety of bedaquiline within a shortened regimen. Bedaquiline is a recently developed drug that has the potential to reduce some of the side effects associated with treatment for MDR-TB.
STREAM aims to generate evidence regarding the safety and effectiveness of shorter, more tolerable MDR-TB regimens, while also improving local capacity to conduct clinical trials. Evidence generated by this trial has and will continue to contribute to development of international and national treatment guidelines.
STREAM began recruiting participants in 2012 and is expected to continue until 2022. To date, the STREAM trial is being carried out in 8 countries and has recruited more than 700 participants.
Stage 1 of the STREAM trial sought to determine whether a 9-month treatment regimen that demonstrated cure rates exceeding 80% during a pilot program in Bangladesh could achieve similar success in other settings. Seven sites in Vietnam, Mongolia, South Africa, and Ethiopia participated in Stage 1. In June 2015, Stage 1 of the trial enrolled its 424th and final patient. The follow-up period (132 weeks) for Stage 1 concluded in January 2018. As of 31st March 2018, the Stage 1 participant retention rate at week 132 exceeded 95%.
Preliminary results for Stage 1 were released at the 48th Union World Conference on Lung Health in Guadalajara in October 2017. According to those preliminary results, the nine-month regimen and the control arm performed about the same (78.1% of assessable participants had a favorable outcome on the nine-month regimen versus 80.6% in the control arm); however, the better than expected results in the control arm mean that preliminary data from STREAM Stage 1 did not demonstrate statistical non-inferiority. Following release of the preliminary results, the World Health Organization conducted a review of the preliminary results and confirmed their 2016 endorsement of the shortened treatment regimen.
"We appreciate the significant work done by the [STREAM] study investigators to generate randomised controlled clinical trial evidence for the shorter regimen," said Dr Tereza Kasaeva, Director of WHO’s Global TB Programme. “Having evidence-based policies is key to improving care for patients affected by the global public health crisis of MDR-TB.”
Final Stage 1 results will be announced at The Union’s World Conference on Lung Health in The Hague in October 2018.
The success of Stage 1 prompted the expansion of the trial to encompass evaluation of other MDR-TB regimens of public health interest during a second stage of the trial.
Stage 2 of STREAM is evaluating the safety and effectiveness of an all-oral nine-month MDR-TB regimen. Enrolment in Stage 2 began in April 2016 in Mongolia, and currently a total of 12 sites in Georgia, Moldova, Mongolia, Ethiopia (two sites), South Africa (four sites), Uganda, and India (two sites) are participating in the trial. As of July 2018, over 300 participants had been enrolled in Stage 2 of the trial. Stage 2 recruitment is expected to finish in 2019, with results available in 2022.
The STREAM Stage 2 Protocol was approved by the US Federal Drug Administration (FDA) and the European Medicines Agency (EMA) for bedaquiline regulatory purposes, as well as The Union’s Ethics Advisory Group.
To learn more about the STREAM trial, watch the video below.