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New drug combination could improve adherence to tuberculosis treatment

23 October 2014

A novel combination of the drugs rifapentine and moxifloxacin can reduce the number of tablets to be taken by patients from 360 to 140 (administered once a week) over the six-month tuberculosis treatment period. This reduction may help patients to adhere to treatment and help to counter the growing problem of drug resistance, which occurs when patients take their medications irregularly. The New England Journal of Medicine published these findings of the EDCTP-funded RIFAQUIN on 23 October 2014.

In the current standard six-month course of tuberculosis treatment, patients need to take four drugs daily for two months followed by two drugs daily for four months – around 360 tablets over a six-month period. The RIFAQUIN trial assessed whether a combination treatment of six or four months duration that included rifapentine (a rifamycin) and moxifloxacin (a quinolone) could reduce the frequency of taking tablets by patients in a six-month treatment by introducing a weekly treatment, or reducing the length of treatment from six months to four months.

The study, led by Dr Amina Jindani (INTERTB Consortium at St George’s, University of London), enrolled 827 patients in trial sites in Botswana, South Africa, Zambia and Zimbabwe. Study participants were assessed 12 months after finishing their treatment. The results show that 95% of patients taking the six-month rifapentine and moxifloxacin combination were cured, which was similar to the standard regimen. Unfortunately, the four-month treatment proved less effective than the six-month treatment.

The new once-weekly drug combination, therefore, could make treatment adherence easier. Dr Jindani said: “Fewer tablets means there is a higher chance of the patient completing their treatment. It also makes it easier for clinics to supervise treatment. This is particularly important for countries where clinics are severely under resourced and where it is not uncommon for patients to travel many miles in order to receive treatment.”

According to the researchers, a number of considerations need further investigation before health services could prescribe the new treatment combination. These include the cost effectiveness of the proposed regimen and the effectiveness of the proposed regimen in HIV-positive patients, who are particularly at risk of tuberculosis.

RIFAQUIN trial

The RIFAQUIN trial was an open-label 3-arm trial to compare a standard tuberculosis treatment regimen with two alternative regimens. It aimed to shorten treatment duration or simplify treatment administration. The trial also evaluated the effect of an increase in rifapentine dose in reducing or eliminating the risk of rifamycin monoresistance in relapse cultures in HIV-positive patients. Further, it evaluated the effect of an increase in rifapentine dose in decreasing the relapse rate so that it would be equivalent to the rate found in a control regimen of rifampicin/isoniazid. It also assessed whether moxifloxacin can substitute for isoniazid in treatment regimens.

The trial involved seven research centres: BOTUSA, Gaborone (Botswana); the Aurum Institute for Health Research and the SATVI Institute of Infectious Diseases & Molecular Medicine (South Africa); the Medical/Malaria Institute at Macha, Macha Mission Hospital (Zambia); and the Biomedical Research and Training Institute, Harare City Health Department and Provincial Medical Directorate Mashonaland East (Zimbabwe).

The study was funded by EDCTP, Medical Research Council (United Kingdom), Sanofi-Aventis (France) and Wellcome Trust (United Kingdom). The RIFAQUIN trial is registered with Current Controlled Trials (number ISRCTN 44153044) and with the Pan African Clinical Trials Registry (number ATMR2008060000861040).

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