Clinical Trials

The Union has played an active role in TB clinical trials since the early 1960s, when it participated in the first international collaborative clinical trial that validated Sir John Crofton's "Edinburgh method" as the gold standard for TB treatment. Subsequent trials studied the efficacy of chemotherapy in previously untreated patients, the reliability of chest X-ray reading and reporting, sputum-smear microscopy, BCG adverse reactions, self-administered versus supervised treatment regimens and other issues.

The Union established the Clinical Trials Division in 1996 to a) initiate and conduct trials of new drugs and/or combined regimens for tuberculosis treatment, b) develop a strong international network of clinical trial centres and c) ensure the ability of its centres to conduct trials meeting the requirements of Good Clinical Practices (GCP) and Good Laboratory Practices (GLP).

Current Trials:

STREAM clinical trial to test first all-oral MDR-TB treatment regimen

In November 2014, The Union announced plans for new clinical research that will evaluate the effectiveness of two new treatment regimens for multidrug-resistant tuberculosis (MDR-TB). If successful, the study will provide robust new evidence on the effectiveness of both an all-oral and a six-month treatment regimen for MDR-TB.
 
The current standard treatment regimen for MDR-TB lasts up to 24 months and requires frequent injections, which pose a significant burden both for patients and for health systems tasked with administering treatment. Permanent hearing loss is a serious side effect of the injected medicines used to treat MDR-TB.
 
The two regimens to be tested in the study include an all-oral 9-month regimen and a 6-month regimen, which will both include bedaquiline, a new novel anti-TB medicine developed by Janssen Research & Development, LLC (Janssen). The Union and the main trial partner, the UK Medical Research Council, will enroll participants in the study from 2015 through the first quarter of 2018, as needed. Results of the study are expected in 2020.
 
The evaluation of these new regimens comprises the second stage of a larger ongoing clinical trial called STREAM, which is testing the effectiveness of shortened treatment regimens for MDR-TB. The second stage of STREAM is the result of innovative partnerships between the United States Agency for International Development (USAID), The Union, and Janssen. Such public-private partnerships are relatively rare in clinical research and are essential to developing new treatments for MDR-TB.

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.

Consistent with the goals of The Union's TREAT TB initiative, the overarching goal of STREAM is to see that research, technology and education are increasingly used to improve the performance of patient management practices in the countries selected for the trial. The outcomes of the study are expected to provide important evidence to inform MDR-TB treatment recommendations from global technical agencies, including the World Health Organization and The Union and national policy and guidelines for MDR-TB treatment in high-burden countries. 

More information about TREAT TB is available at treattb.org