The results of the RIFAQUIN trial, published today in the New England Journal of Medicine, show that a novel combination of drugs can dramatically reduce how often TB patients need to take medication over a six-month period.
The standard regimen for TB involves a combination of drugs, taken every day for 6 months. This treatment is effective if taken regularly, but the length and frequency of dosing of the treatment places substantial burdens on the health system and it is demanding for patients to adhere to daily. Failure to do so results in a growing problem of drug resistance.
RIFAQUIN was a randomised controlled trial which investigated whether a new combination of drugs, moxifloxacin and rifapentine, would allow doctors to reduce how often patients have to take tablets over a course of TB treatment. They also tested whether it would be possible to reduce the duration of treatment from six to four months. The two new regimens which were compared to the current 6-month daily regimen were:
· A new six-month regimen, in which participants took a combination of four drugs every day for two months followed by moxifloxacin and high dose rifapentine once a week for four months.
· A four-month regimen in which participants took the same combination of four drugs every day for two months followed by moxifloxacin and rifapentine twice a week for two months.
The trial was carried out in South Africa, Zimbabwe, Botswana and Zambia, and involved 827 participants, of whom 233 were HIV positive. Participants were followed up for at least 12 months, with the majority to 18 months.
RIFAQUIN found that the new six-month regimen was as good as the standard daily regimen; it was also safe and well tolerated, and none of the participants became resistant to the drugs. The new six-month regimen reduces the number of tablets needed in a course of treatment from 360 to 140, and reduces how often patients need to take tablets over the final four months from every day to once a week.
These results could potentially make TB treatment easier for patients, carers and the health system; for example if patients no longer have the burden of daily travel to a health facility during the final four months of treatment. Because the regimen does not include isoniazid, the new regimen would also be of particular interest in areas where there are high levels of isoniazid resistance, such as the UK.
Disappointingly, researchers found that the shorter, four-month treatment regimen was not as good as the standard six-month daily treatment. This result is consistent with the findings of two other recent trials (REMoxTB and OFLOTUB) published in the same issue of the journal, that were also assessing the possibility of reducing TB treatment from six to four months .
The RIFAQUIN study was led by researchers at St George’s, University of London in collaboration with the Medical Research Council Clinical Trials Unit at UCL, and researchers in Botswana, South Africa, Zambia and Zimbabwe. It was funded by the European and Developing Countries Clinical Trials Partnership (EDCTP) with the support of the Wellcome Trust. Drugs were donated by Sanofi-Aventis, Genus Pharmaceuticals and Sandoz SA.