Abstract
The safety of artemether-lumefantrine in patients with acute, uncomplicated Plasmodium falciparum malaria was investigated prospectively using the auditory brainstem response (ABR) and pure-tone thresholds. Secondary outcomes included polymerase chain reaction-corrected cure rates. Patients were randomly assigned in a 3:1:1 ratio to either artemether-lumefantrine (N = 159), atovaquone-proguanil (N = 53), or artesunate-mefloquine (N = 53). The null hypothesis (primary outcome), claiming that the percentage of patients with a baseline to Day-7 ABR Wave III latency increase of > 0.30 msec is ≥ 15% after administration of artemether-lumefantrine, was rejected; 2.6% of patients (95% confidence interval: 0.7-6.6) exceeded 0.30 msec, i.e., significantly below 15% (P < 0.0001). A model-based analysis found no apparent relationship between drug exposure and ABR change. In all three groups, average improvements (2-4 dB) in pure-tone thresholds were observed, and polymerase chain reaction-corrected cure rates were > 95% to Day 42. The results support the continued safe and efficacious use of artemether-lumefantrine in uncomplicated falciparum malaria.
Publication types
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Randomized Controlled Trial
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Research Support, Non-U.S. Gov't
MeSH terms
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Adolescent
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Adult
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Aged
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Antimalarials / administration & dosage
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Antimalarials / adverse effects*
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Antimalarials / therapeutic use
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Artemether, Lumefantrine Drug Combination
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Artemisinins / administration & dosage
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Artemisinins / adverse effects*
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Artemisinins / therapeutic use
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Artesunate
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Atovaquone / administration & dosage
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Atovaquone / adverse effects
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Atovaquone / therapeutic use
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Audiometry
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Child
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Colombia
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Drug Combinations
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Drug Therapy, Combination
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Ethanolamines
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Evoked Potentials, Auditory, Brain Stem / drug effects*
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Female
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Fluorenes / administration & dosage
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Fluorenes / adverse effects*
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Fluorenes / therapeutic use
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Humans
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Malaria, Falciparum / drug therapy*
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Malaria, Falciparum / parasitology
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Male
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Mefloquine / administration & dosage
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Mefloquine / adverse effects
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Mefloquine / therapeutic use
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Middle Aged
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Plasmodium falciparum / drug effects
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Proguanil / administration & dosage
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Proguanil / adverse effects
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Proguanil / therapeutic use
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Prospective Studies
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Treatment Outcome
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Young Adult
Substances
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Antimalarials
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Artemether, Lumefantrine Drug Combination
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Artemisinins
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Drug Combinations
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Ethanolamines
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Fluorenes
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atovaquone, proguanil drug combination
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Artesunate
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Proguanil
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Mefloquine
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Atovaquone