Randomized, prospective, three-arm study to confirm the auditory safety and efficacy of artemether-lumefantrine in Colombian patients with uncomplicated Plasmodium falciparum malaria.
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.
Fundación Santa Fe de Bogotá, Bogotá, Colombia. Gabriel.Carrasquilla@fsfb.org.co
Gabriel
G
Carrasquilla
Clemencia
C
Barón
Edwin M
EM
Monsell
Marc
M
Cousin
Verena
V
Walter
Gilbert
G
Lefèvre
Oliver
O
Sander
Laurel M
LM
Fisher
D000293:Adolescent; D000328:Adult; D000368:Aged; D000962:Antimalarials / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000077332:Artesunate; D053626:Atovaquone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001299:Audiometry; D002648:Child; D003105:Colombia; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D004983:Ethanolamines; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects*; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D015767:Mefloquine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000187:drug effects; D002727:Proguanil / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011446:Prospective Studies; D016896:Treatment Outcome; D055815:Young Adult
D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; C109496:atovaquone, proguanil drug combination; D000077332:Artesunate; D002727:Proguanil; D015767:Mefloquine; D053626:Atovaquone