06 April 2023 | Thursday | Analysis
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The TRUNCATE-TB trial recruited 675 people who were diagnosed with pulmonary TB and randomly allocated them to receive the standard treatment for six months or to receive the TRUNCATE strategy which involves initial treatment with an intensive two-month (8-week) antibiotic regimen, with the possibility of extension if needed, followed by close monitoring and early retreatment for those who were not cured. The team tested the strategy with four different initial 8-week drug combinations using a new type of trial design to identify whether any of the treatment combinations were doing less well and needed to be discontinued early. Participants in the trial were each followed up for 2 years to see how many patients were still on treatment for TB or had active TB at that time.
In the final analysis, two of the strategy groups were compared against the standard treatment group. One of these strategy groups – in which people were given an initial 8-week treatment combination containing bedaquiline1 and linezolid with three standard tuberculosis drugs (isoniazid, pyrazimamide and ethambutol) – was found to be as good as the standard treatment in clinical outcome at 2 years. But, in this strategy group the average total time on treatment was 85 days, compared to 180 days for standard treatment group.
Professor Nicholas Paton said, “This trial shows that it is possible to move away from the standard six-month, one-treatment-duration-for-all approach which is long and may not be needed for everyone. Instead, we can treat most people with a two-to-three-month intensified treatment, provided that they remain in clinical care for monitoring after the end of treatment
so that the minority who are not completely cured and require longer treatment can be detected and re-treated. This trial has the potential to transform the way people think about treating tuberculosis, and the way that clinical trials are done. With further work to refine the strategy, this new, more individualised approach to treatment will likely replace the standard six-month fixed duration approach for all.”
1 Bedaquiline is FDA-registered (since Dec 2012) for multi-drug resistant TB and is currently not registered in Singapore.
TB is caused by a Mycobacterium tuberculosis bacterial infection that affects the lungs, which multiplies and destroy the tissues in the body. As an infectious disease, TB germs can be transmitted through the air when a TB patient coughs, sneezes, speaks or sings and remain in the environment for a few hours at a time. The standard for TB treatment globally has been a six-month regimen based around the antibiotic rifampicin (called “rifampin” in the United States).
The TRUNCATE-TB trial was designed and coordinated from Singapore across a network of 18 sites in Indonesia, Philippines, Thailand, India and Uganda, Africa. This multi-site trial was supported by SCRI, which provided support in patient randomisation, data management, pharmacovigilance, and statistical analysis.
The TRUNCATE-TB trial is supported by the National Research Foundation, Singapore, under its Translational and Clinical Research Flagship Programme (NMRC/TCR/011-NUHS/2014), and administered by the Singapore Ministry of Health’s National Medical Research Council. It is also funded by the United Kingdom’s Medical Research Council and the Department for International Development, as well as Wellcome Trust.
The findings are published in the New England Journal of Medicine.