STREAM Stage 2

What was this study about?

STREAM Stage 2 assessed two new short course regimens for multidrug-resistant tuberculosis (MDR-TB) in comparison with the 9-month regimen developed in Bangladesh which was evaluated in STREAM Stage 1.

In the 9-month oral regimen the new drug bedaquiline was given throughout treatment in place of the injectable kanamycin which frequently gives rise to unpleasant side-effects such as deafness. High dose moxifloxacin was replaced by levofloxacin to minimise potential cardiac side-effects such as QT prolongation.

The 6-month regimen had a shorter intensive phase, and as in the 9-month oral regimen bedaquiline was given throughout treatment and levofloxacin replaced moxifloxacin. Prothionamide and ethambutol were both dropped.

The primary objective of the study was to assess whether the fully oral regimen was non-inferior to the 9-month regimen studied study in Stage 1.

Publications from this study

Moodley Riya, Godec Thomas R on behalf of STREAM Trial Team. Short-course treatment for multidrug-resistant tuberculosis: the STREAM trials. Eur Respir Rev 2015; 25: 29-35 [ERS Publications]

Long-term efficacy and safety of two short standardised regimens for the treatment of rifampicin-resistant tuberculosis (STREAM stage 2): extended follow-up of an open-label, multicentre, randomised, non-inferiority trial. Lancet Respir Med 2024; 12: 975–87 

What difference did this study make?

The STREAM stage 2 study shows that at 132 weeks from randomisation, both a 9-month oral bedaquiline-containing regimen and a 6-month bedaquiline-containing regimen with 8 weeks of a second-line injectable had superior favourable outcomes compared with a 9-month injectable-based regimen, with very little acquisition of phenotypic resistance to core drugs and no evidence that bedaquiline increases the risk of death. STREAM stage 2 currently has the longest follow-up data of a randomised comparison of bedaquiline to a robust control regimen.

The findings of the STREAM stage 2 trial, combined with results of previous trials, show that shorter bedaquiline-containing regimens are an effective and safe treatment for patients with multidrug-resistant tuberculosis. These data confirm the value of the 9-month regimen recommended in current WHO guidelines and support the use of a 6-month regimen.

Type of study

Randomised trial

Contact details

mrcctu.ctuenquiries@ucl.ac.uk

Who funded the study?

Stage 2 was funded by the United States Agency for International Development (USAID) and Janssen Pharmaceuticals and sponsored by The International Union Against Tuberculosis and Lung Disease.