The STREAM Stage 1 results show that the efficacy of the 9-11-month STREAM treatment regimen is comparable to that of the 20-month treatment regimen recommended in the 2011 WHO guidelines.

AHRI Tuberculosis Hospital, Addis Ababa, Ethiopia. STREAM MDR-TB inpatients ward.

Stage 1 of the STREAM trial closed to recruitment in 2016, with 424 participants. It aimed to determine whether a 9-11-month treatment regimen that demonstrated cure rates exceeding 85 percent during a pilot program in Bangladesh, was as effective as the longer regimen under clinical trial conditions. Seven sites in Vietnam, Mongolia, South Africa, and Ethiopia participated in Stage 1 of the trial.

Efficacy and safety of 9-11-month regimen is comparable to the 20-month regimen

The results of STREAM Stage 1, published in the New England Journal of Medicine, showed that the 9-11-month regimen was statistically non-inferior to the 20-month regimen, in terms of efficacy (78.8 percent of assessable participants had a favorable outcome, compared to 79.8 percent in the longer regimen.) In other words, the efficacy of the 9–11-month regimen is comparable to that of the 20-month regimen. There was no evidence that efficacy results were worse in HIV-infected participants compared to HIV-negative participants.

There were very similar rates of grade 3-5 adverse events between with two arms, with 48.2% of participants who received the 9-11-month regimen compared to 45.4% in the 20-month regimen.  The most common grade 3-5 adverse events were cardiac conduction disorders which increases the risk of serious and potentially fatal arrhythmias (10% in the 9-11 month regimen vs 5% in the 20-month regimen),  and of metabolism and nutrition disorders (15% in the 9-11 month regimen, and 20% in the 20-month regimen).

The work carried out as part of the STREAM Trial has influenced current WHO guidelines and supported the move away from the previously recommended 20-month regimen. The 20-month regimen had a number of important drawbacks, including the duration of treatment, the significant side-effects of the drugs used, poor cure rates, and the cost of treatment.

The STREAM Stage 1 results support the use of a shortened regimen for patients with rifampicin-resistant TB.

Until now there has been a lack of strong supporting evidence to underpin MDR-TB treatment guidelines. The results from STREAM Stage 1 help to fill that gap.

Dr I.D. Rusen, Project Director for the STREAM Trial.

Significant advantages of the shorter regimen

The STREAM 9–11-month regimen presents substantial advantages, as it reduces treatment times, decreases the overall pill burden for patients and may improve retention under programmatic conditions. Furthermore, although analysis of health economics data is ongoing, the 9–11-month regimen provides potential cost savings to patients and health systems compared to the 20-month regimen.

The continuing importance of STREAM Stage 2

There remains an urgent need to improve the efficacy and safety of MDR-TB treatment, and further research into shorter regimens is vitally important. STREAM Stage 2 is evaluating an all oral regimen that is potentially as effective and more tolerable than the injectable-containing regimens currently in use.  STREAM Stage 2 is also evaluating whether the fully oral 9–11-month regimen will result in cost-savings for patients and/or health systems, and includes a health-related quality of life assessment.  Stage 2 of the STREAM trial is expected to contribute important evidence for future policy decisions regarding injectable-free, all-oral MDR-TB regimens. Those regimens could revolutionize treatment for MDR-TB patients around the world, offering a shorter, less onerous and more cost-effective alternative.

To read more about the STREAM Trial, click here.