Stage 1 of the STREAM Trial sought to determine whether a 9-month treatment regimen that demonstrated cure rates exceeding 80% during a pilot programme in Bangladesh could achieve similar success in other settings. The objectives are to determine whether the proportion of patients with a successful outcome on the shorter treatment regimen is at least as good as that observed in the longer control regimen.
The reason for this “non-inferiority” design of the trial is that, with its considerably reduced pill burden and duration – as well as the expected increase in adherence – the shorter regimen needs only to show that it is not less effective than the control regimen to become the new standard.
Ethiopia, Mongolia, South Africa and Viet Nam participated in Stage 1 of the trial. On 30 June 2015, the trial enrolled its 424th patient, the last patient to be recruited for Stage 1.
Stage 1 was funded through the TREAT TB cooperative agreement with the U.S. Agency for International Development (USAID). Additional funding from the UK Medical Research Council and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement.
The Stage 1 results are expected to be ready in early 2018.
The success of Stage 1 implementation has also led to the opportunity to test two other regimens of particular public health interest and relevance.
In March 2016, the STREAM research team had begun Stage 2 of the trial, which will enroll a total of 1155 patients. In Stage 2, the randomization includes two additional regimens, both of which will be compared to the 9-month regimen from Stage 1. The WHO control regimen is also continued in Stage 2. Both of the new regimens will include a recently licensed drug called bedaquiline.
The first of the new regimens will be completely oral. The injectable medicine used in Stage I regimen, called kanamycin, will be replaced with bedaquiline in Stage 2. The second new regimen will be 6 months in duration and kanamycin will be given for only 2 months.
The STREAM Stage 2 Protocol has been 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.
STREAM Stage 2 is the result of a unique collaboration between USAID, Janssen Pharmaceuticals and The Union/Vital Strategies.
The results of Stage 2 are expected to be available in 2021.