NECT |
NECT: Nifurtimox-eflornithine combination trial for HAT
The currently available medicines for late-stage human HAT are very toxic, difficult to administer under field conditions and show decreasing efficacy against the parasites. Because there are no alternative solutions in the short- and mid-term, clinical studies are underway to explore therapeutic combinations of existing drugs. Of the possible combinations, eflornithine-nifurtimox has shown the least treatment-associated toxicity and mortality, as well as adequate efficacy.
On behalf of DNDi, the PMU was contributing to a Phase III multicentre, randomised, open-label, clinical non-inferiority study comparing the therapeutic efficacy and clinical safety of an abridged regimen of intravenous (iv) eflornithine plus oral nifurtimox to the standard iv eflornithine regimen (NECT).
Building on the initial, single-centre study set up by Médecins Sans Frontières (MSF) and Epicentre in Nkayi, the Republic of the Congo (RoC), DNDi sponsored the extension of the study into a multicenter trial with additional sites in the DRC. MSF, the PMU and the national sleeping sickness control programmes managed, implemented and monitored the study in selected HAT treatment centres in the RoC and the DRC. In collaboration with the DRC HAT control programme (PNLTHA), PMU set up two study sites, Dipumba and Katanda in the East Kasaï province. Both sites were substantially refurbished by DNDi, and PMU installed trial-related equipment and provided relevant training and support. Logistical support was provided by the STI and DNDi local offices in Kinshasa, and the different subsections of MSF in the DRC.
Enrolment in the nifurtimox-eflornithine combination therapy (NECT) trial was successfully concluded by late 2006 and the follow-up by mid-2008. A total of 287 patients were treated. Patient and staff compliance was excellent; moreover, the combination regimen is favoured as it is simpler to apply and hospitalisation time is much reduced. Positive preliminary results were recently published, and the final results and study report will be available by the second half of 2009. The therapeutic non-inferiority could be shown, therefore the combination regimen may become an alternative therapy with simpler administration, shorter hospitalisation, lower cost and protection against the emergence of resistance.
Subsequently nifurtimox was submitted for the addition to the WHO Model list of essential medicines (EML) for stage 2 Trypanosoma brucei gambiense HAT to be used in association with eflornithine. The expert meeting’s decision is expected to be communicated in the first half of 2009 which should enable WHO/NTD to recommend the combination treatment to the countries.
