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 with a number of goals. Firstly, to initiate and conduct trials of new drugs and/or combined regimens for tuberculosis treatment; secondly, to develop a strong international network of clinical trial centres; and finally, to 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

Multidrug-resistant tuberculosis (MDR-TB) is a global public health crisis, with almost half a million people developing MDR-TB in 2016. The 2011 WHO TB treatment guidelines recommended a regimen that lasts 20-24 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 Standardised Treatment Regimen of Anti-TB Drugs for Patients with MDR-TB (STREAM) trial is the world’s first multi-country randomised clinical trial to test the efficacy, safety and economic impact of shortened MDR-TB treatment regimens.

STREAM was initiated by The Union in 2012 with its main partner, the Medical Research Council Clinical Trials Unit at University College London (UCL), and now implemented with various global partners including Vital Strategies.

STREAM Stage 1

Stage 1 of the STREAM Trial seeks to determine whether a nine-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 not inferior to the longer control regimen. It was felt that even if the nine-month regimen is not superior to the 20-24 month regimen, as long as it is not inferior, it would be a major advance.

Ethiopia, Mongolia, South Africa and Vietnam 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.

STREAM stage 1 preliminary results, released 13 October 2017 at the 48th Union World Conference on Lung Health, demonstrate that the nine-month treatment regimen being tested has achieved favourable outcomes in almost 80 percent of those treated.

The results suggest the efficacy of the nine-month regimen in the trial will be very close to the longer regimen currently recommended by WHO, but, statistically, we are not currently able to say the nine-month regimen is equivalent to the longer regimen  (78.1 percent of patients receiving the nine-month regimen achieved a favourable outcome, compared to 80.6 percent of patients receiving the 20-24 month regimen).

I.D. Rusen, Union lead for the STREAM trial said: “The nine-month regimen did as well or even better than expected given the rigorous standards of the clinical trial, but the 20-24 month regimen did much better than routinely reported outcomes from programme settings.

“The trial setting meant that more patients completed treatment on the 20-24 month regimen than we know is often the case in most real life settings. In routine programmes unable to achieve the high STREAM retention rates, the nine-month regimen may actually perform better in comparison to the 20-24 month regimen.”

The Union’s response to these preliminary results can be read here. Full Stage 1 results are expected to be released in 2018.

STREAM Stage 2

Stream Stage 2 introduces the use of bedaquiline, produced by Janssen Therapeutics, Division of Janssen Products, LP, one of the Janssen Pharmaceutical Companies of Johnson & Johnson, as part of the shorter treatment regimen being tested. Stage 2, in collaboration with Janssen and implemented by Vital Strategies, is the first phase III clinical trial to test the effectiveness of bedaquiline within a shortened MDR-TB treatment regimen.

Bedaquiline, is a diarylquinoline antimycobacterial agent developed by Janssen for the treatment of MDR-TB as part of a combination therapy. By 2016, at least 35 countries have introduced shorter regimens for treatment of MDR/RR-TB and 89 countries and territories had started using bedaquiline. (WHO Global TB Report 2017)

The first patients participating in Stage 2 enrolled at a clinical trial site in Mongolia in April 2016. STREAM is the first clinical trial of its kind in Mongolia.

Stage 2 is now underway in Mongolia, Ethiopia and South Africa, with trial initiation planned to roll out in China, Georgia, India, Indonesia, Moldova, Uganda and Vietnam.

STREAM is the most significant project carried out by the TREAT TB programme -  a USAID-supported initiative focused on providing Technology, Research, Education and Technical Assistance for TB to improve treatment and control worldwide. TREAT TB aims to contribute to new knowledge through field evaluations of diagnostic tools, clinical trials of priority research questions and targeted operational research that benefits global, regional and country TB control efforts. TREAT TB is implemented by The Union, Vital Strategies and other key global partners

More information about TREAT TB is available at treattb.org