Four Artemisinin Based Treatments in African Pregnant Women with Malaria.
BACKGROUND Information regarding the safety and efficacy of artemisinin combination treatments for malaria in pregnant women is limited, particularly among women who live in sub Saharan Africa. METHODS We conducted a multicenter, randomized, open label trial of treatments for malaria in pregnant women in four African countries. A total of 3428 pregnant women in the second or third trimester who had falciparum malaria (at any parasite density and regardless of symptoms) were treated with artemether lumefantrine, amodiaquine artesunate, mefloquine artesunate, or dihydroartemisinin piperaquine. The primary end points were the polymerase chain reaction (PCR) adjusted cure rates (i.e. cure of the original infection; new infections during follow up were not considered to be treatment failures) at day 63 and safety outcomes. RESULTS The PCR adjusted cure rates in the per protocol analysis were 94.8% in the artemether lumefantrine group, 98.5% in the amodiaquine artesunate group, 99.2% in the dihydroartemisinin piperaquine group, and 96.8% in the mefloquine artesunate group; the PCR adjusted cure rates in the intention to treat analysis were 94.2% 96.9% 98.0% and 95.5% respectively. There was no significant difference among the amodiaquine artesunate group, dihydroartemisinin piperaquine group, and the mefloquine artesunate group. The cure rate in the artemether lumefantrine group was significantly lower than that in the other three groups, although the absolute difference was within the 5 percentage point margin for equivalence. The unadjusted cure rates, used as a measure of the post treatment prophylactic effect, were significantly lower in the artemether lumefantrine group (52.5% than in groups that received amodiaquine artesunate (82.3% dihydroartemisinin piperaquine (86.9% or mefloquine artesunate (73.8% No significant difference in the rate of serious adverse events and in birth outcomes was found among the treatment groups. Drug related adverse events such as asthenia, poor appetite, dizziness, nausea, and vomiting occurred significantly more frequently in the mefloquine artesunate group (50.6% and the amodiaquine artesunate group (48.5% than in the dihydroartemisinin piperaquine group (20.6% and the artemether lumefantrine group (11.5% (P<0.001 for comparison among the four groups) CONCLUSIONS Artemether lumefantrine was associated with the fewest adverse effects and with acceptable cure rates but provided the shortest post treatment prophylaxis, whereas dihydroartemisinin piperaquine had the best efficacy and an acceptable safety profile. (Funded by the European and Developing Countries Clinical Trials Partnership and others; ClinicalTrials.gov number, NCT00852423.
The New England journal of medicine