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MAMS-TB study finds high-dose rifampicin may help shorten TB treatment

10 June 2015

In February 2015, researchers presented the results of the MAMS-TB study at a conference in Seattle, Washington.  The study found that a high dose of the drug rifampicin helps to kills tuberculosis (TB) bacteria faster than the current standard treatment.

The World Health Organization (WHO) currently recommends treating TB with a combination of four drugs (ethambutol, isoniazid, pyrazinamide and rifampicin).  People with TB take all four drugs every day for two months.  For the next four months, they continue to take rifampicin and another of the drugs, isoniazid, every day.

For a 12-week period, some of the patients in the MAMS-TB study were given the standard dose of three of the drugs: isoniazid, ethambutol and pyrazinamide.  However, instead of taking the standard dose of rifampicin, these patients took a high dose.

MAMS-TB found that this new combination of drugs killed the TB bacteria faster than the standard treatment, and was as safe as the current standard treatment.  After 12 weeks, researchers were unable to detect TB bacteria in 80% of the patients who took high-dose rifampicin, which compares to 70% of the patients who took the standard, WHO-recommended treatment. 
The current standard treatment means that people with TB have to take drugs daily for six months, which can make it difficult for patients to stick to the treatment plan.  TB treatment also has significant costs, both for the health system and for patients. Reducing the amount of time it takes to treat TB would not only make it easier for patients to take their treatment but might also reduce the cost of treatment.

The results of the MAMS-TB study do not mean that TB treatment can be shortened right away, but the findings are a first step towards this goal.  The MAMS-TB study was a phase II trial, and further trials (phase III) will be needed to see if using a high dose of rifampicin can actually shorten treatment.

Martin Boeree, the Chief Investigator for the MAMS-TB study said: "This is the largest reduction in time to culture conversion seen in any previous TB trial, to our knowledge."  Culture conversion is a test used to indicate the progress of TB treatment for a particular patient.  He also noted that, "High doses of rifampicin may be an important component in shorter TB regimens in the future."

365 patients from seven sites in Tanzania and South Africa took part in the MAMS-TB trial.  The trial aimed to identify combinations of drugs that could shorten TB treatment, by comparing four new combinations of drugs with the standard six-month combination.

It used the innovative 'multi-arm, multi-stage' approach, which allows several treatments to be assessed against a single control arm, and is a more efficient use of time and resources than traditional 'two-arm' trials.  Patrick Phillips, Senior Statistician at the MRC Clinical Trials Unit at UCL, said that: "To our knowledge, this is the first trial with an adaptive design evaluating multiple combination treatment regimens in a global health setting.  We have shown that novel trial methodology originally developed for oncology [cancer] trials can be successfully used to evaluate new treatments for tuberculosis."

The MAMS-TB trial was carried out by the PanACEA consortium (Pan African Consortium for the Evaluation of Anti-tuberculosis agents).  PanACEA is a partnership of 11 African and seven European institutions, which aims to shorten and simplify the treatment of TB and to develop a sustainable TB clinical trials network in Africa.  UCL is a major partner in the PanACEA consortium.