Arterolane-Piperaquine-Mefloquine Noninferior to Current Therapies for Uncomplicated Malaria in Children

The efficacy of arterolane-piperaquine-mefloquine was found to be noninferior to that of arterolane-piperaquine and artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malarial infection in children when dosed according to weight.

In a randomized, open-label, single-center, noninferiority trial of 217 children in Kenya, investigators enrolled patients aged 2 to 12 years who had uncomplicated P falciparum infection from March 2018 through May 2019. All patients received their respective treatment arm therapies for 3 consecutive days and a single low dose of oral primaquine 24 hours after treatment initiation.

Patients in the arterolane-piperaquine-mefloquine arm (n=72) received the following medications once daily with a nonfatty snack or water: arterolane 4 mg/kg, piperaquine  20 mg/kg, and mefloquine 8 mg/kg.

Patients in arterolane-piperaquine arm (n=73) received the following medications once daily with a nonfatty snack or water: arterolane 4 mg/kg and piperaquine 20 mg/kg.

Patients in the artemether-lumefantrine arm (n=72) received the following medications twice daily with a fatty snack or drink: artemether 5 to 24 mg/kg and lumefantrine 29 to 144 mg/kg.

The primary endpoint was 42-day polymerase chain reaction (PCR)-corrected efficacy, defined as “the absence of treatment failure in the first 42 days after treatment of arterolane-piperaquine-mefloquine versus artemether-lumefantrine.” The 42-day PCR-corrected efficacy for the arterolane-piperaquine-mefloquine arm was 100% (95% CI, 95-100); for arterolane-piperaquine was 100% (95% CI, 95-100); and for artemether-lumefantrine was 96% (95% CI, 88-99). The 42-day PCR-corrected efficacy of arterolane-piperaquine-mefloquine was found to be noninferior to that of artemether-lumefantrine (risk difference, 4%; 95% CI, 0-9; P =.25).

Prolongation of the QTcB interval at hour 52 was found to be significantly greater in the arterolane-piperaquine arm (mean increase, 18.9 ms; standard deviation [SD], 19.9; P <.0001) and the arterolane-piperaquine-mefloquine arm (mean increase, 15.7 ms; SD, 23.4; P =.0007) than in the artemether-lumefantrine arm (mean increase, 3.6 ms; SD, 16.3). Rates of vomiting were significantly higher in the arterolane-piperaquine arm (P =.0013) and the arterolane-piperaquine-mefloquine arm (P =.0006) than in the artemether-lumefantrine arm.

“Combining arterolane with two partner drugs in a triple therapy could preserve the efficacy of each individual drug, as the chance of parasites developing resistance to all three drugs is the product of the chance of developing resistance to each individual drug, assuming there are no interactions between resistance mechanisms. The cost of a triple antimalarial therapy will be slightly higher than the cost of a standard artemisinin-based combination therapy. However, these increases in costs should be considered against the costs associated with the emergence of multidrug-resistant malaria, which would probably increase the morbidity and mortality of malaria and could set back successes in malaria control and elimination,” study authors concluded.

Reference

Hamaluba M, van der Pluijm RW, Weya J, et al. Arterolane-piperaquine-mefloquine versus arterolane-piperaquine and artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Kenyan children: a single-centre, open-label, randomised, non-inferiority trial. Lancet Infect Dis. Published online June 7, 2021. doi:10.1016/S1473-3099(20)30929-4