The 9 month versus the 20 month treatment regimen for MDR-TB - what the randomized clinical trial says

17 October 2017 - Geneva, Switzerland - The Stop TB Partnership recognized the preliminary results from Stage 1 of the STREAM clinical trial which shows that the nine-month treatment regimen being tested achieved favorable outcomes in almost 80 percent of those treated. The results were announced at the Union World Conference on Lung Health in Guadalajara, Mexico last week.

Welcoming the results from the trial, Dr Lucica Ditiu, Executive Director of the Stop TB Partnership said: "We need shorter and better regimens to treat people affected by MDR TB and the preliminary results of the first multi-country randomized clinical trial gives everyone hope and need for action and speed. Currently, with the 20-24 months regimens we have a very challenging situation of just 50% treatment success rate - linked to several reasons but especially to the duration and complications of treatment. A 9 month regimen will fix many of these issues".

The results suggest the nine-month regimen is very close to the effectiveness of the 20-24 month regimen recommended in the 2011 WHO guidelines, when both regimens are given under trial conditions. The STREAM trial is the world’s first multi-country randomized clinical trial to test the efficacy, safety and economic impact of shortened multidrug-resistant (MDR-TB) treatment regimens.

MDR-TB, defined as forms of TB that are resistant to at least the two first-line antibiotics isoniazid and rifampicin, affected an estimated 480,000 people in 2015 and has been declared a public health crisis by the World Health Organization (WHO). The 20-month regimen used in many countries globally is costly, has significant side effects and the length of the regimen makes it hard for both patients and the health system. The regimen has an average global treatment success rate of only around 50 percent when used in real-world treatment settings.

Because of these widely-acknowledged challenges, in 2016 the WHO guidelines were updated to recommend a shorter, nine-12 month regimen for most people with MDR-TB. The guidelines acknowledge that this recommendation is based on very low certainty in the evidence.

In STREAM Stage 1, 424 patients from Ethiopia, Mongolia, South Africa and Vietnam were randomly allocated to receive either:

The results suggest the efficacy of the nine-month regimen in the trial will be very close to the longer regimen recommended in the 2011 WHO guidelines, but, statistically, the trial results are not able to confirm if the nine-month regimen is non-inferior to the longer regimen.

The preliminary results also show that electrocardiogram (ECG) monitoring was very useful, and required throughout treatment. This was done effectively during the trial, and close monitoring would also be necessary with regimen use in routine programme settings. In terms of the economic burden of MDR-TB, the results show the nine-month regimen reduces costs to both the health system and patients, compared to the 20-month regimen.

Follow-up of Stage 1 is ongoing, and full results will be published next year, which will include data from the final follow-up visits. These additional data are unlikely to materially change the results.

The STREAM trial is currently implemented by The Union, the Medical Research Council Clinical Trials Unit at UCL and several key partners. Vital Strategies, based in New York, is supporting several important areas of the trial including pharmaceutical management and community engagement. Other collaborating partners include Institute of Tropical Medicine and Liverpool School of Tropical Medicine.