STREAM stage 2 study finds all-oral and six-month treatment regimens to be safe and effective
08 Nov 2022
Results from Stage 2 of the STREAM trial show that two new shortened treatment regimens containing the drug bedaquiline are both safe and effective in treating rifampicin-resistant tuberculosis (RR-TB). The costs of the new regimens are also lower for patients. These results were presented yesterday at The Union World Conference on Lung Health, and published in The Lancet on 8th November.
The results show that both a fully-oral (no injections) 9-month regimen and a 6-month regimen (with injections given for eight weeks) were more effective than the control regimen, which was a 9-month regimen that included injections.
RR-TB, is a form of TB that is resistant to rifampicin, one of the core drugs used for treating TB. This makes it difficult to treat. Over half a million people were estimated to have RR-TB in 2020.
Despite recent advances in the treatment of RR-TB, guidelines have been based largely on observational and non-randomized clinical trial data. The STREAM Stage 2 results provide randomised clinical trial data to strengthen the evidence base for treatment recommendations.
Participants were recruited from eight countries on three continents. People who agreed to take part in STREAM Stage 2 were randomly allocated to one of four treatment regimens:
- the WHO 20-24 month regimen recommended in 2011
- an all-oral 9-month regimen (containing the new anti-tuberculosis drug bedaquiline)
- a 6-month injection-containing regimen (containing bedaquiline)
- a 9-month control regimen (which was studied in Stage 1, and contained injections)
Allocation to the WHO regimen stopped early following the 2016 WHO recommendations of a shorter regimen.
The research builds on the findings from Stage 1 of the STREAM trial, which demonstrated that a 9-month regimen (that contained injections but did not contain bedaquiline) was non-inferior to the 20-24 month regimen recommended in the 2011 WHO guidelines at the time the trial began.
STREAM Stage 2 demonstrated that the fully-oral 9-month regimen was significantly more effective than the 9-month control regimen. 82.7% of participants receiving the fully-oral regimen had a favorable outcome compared to 71.1% receiving the control regimen.
It also found that the 6-month regimen was also more effective than the control regimen. 91.0% of participants receiving the 6-month regimen had a favorable outcome compared to 68.5% in concurrent controls.
While many participants experienced side-effects, there was no evidence of these being worse in either of the two new treatments compared to the control treatment. STREAM Stage 2 also found that fewer participants experienced severe hearing loss in the all-oral regimen (2%) and the six-month regimen (4%) compared to the control regimen (8%). This is important information, as hearing loss has been a particular concern for patients taking earlier MDR-TB treatments.
The health economics study that was conducted as part of STREAM Stage 2 found that the fully-oral treatment is more expensive than the control regimen from a health system perspective. This was largely driven by the cost of the regimen. However, costs to patients were lower in both study regimens compared to the control regimen. This is important as MDR-TB can lead to patients facing catastrophic costs.
STREAM Stage 2 was conducted in Ethiopia, Georgia, India, Moldova, Mongolia, South Africa, and Uganda.
Stage 2 of STREAM was jointly funded by USAID and Janssen Research & Development, LLC. Additional funding for STREAM was provided by the Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement and is also part of the EDCTP2 programme supported by the European Union.