@article{fdi:010046164,
  title = {{R}andomized, multicentre assessment of the efficacy and safety of {ASAQ} - a fixed-dose artesunate-amodiaquine combination therapy in the treatment of uncomplicated {P}lasmodium falciparum malaria},
  author = {{N}diaye, {J}. {L}. and {R}andrianarivelojosia, {M}. and {S}agara, {I}. and {B}rasseur, {P}hilippe and {N}diaye, {I}. and {F}aye, {B}. and {R}andrianasolo, {L}. and {R}atsimbasoa, {A}. and {F}orlemu, {D}. and {M}oor, {V}. {A}. and {T}raore, {A}. and {D}icko, {Y}. and {D}ara, {N}. and {L}ameyre, {V}. and {D}iallo, {M}. and {D}jimde, {A}. and {S}ame-{E}kobo, {A}. and {G}aye, {O}.},
  editor = {},
  language = {{ENG}},
  abstract = {{B}ackground: {T}he use of artemisinin derivative-based combination therapy ({ACT}) such as artesunate plus amodiaquine is currently recommended for the treatment of uncomplicated {P}lasmodium falciparum malaria. {F}ixed-dose combinations are more adapted to patients than regimens involving multiple tablets and improve treatment compliance. {A} fixed-dose combination of artesunate + amodiaquine ({ASAQ}) was recently developed. {T}o assess the efficacy and safety of this new combination and to define its optimum dosage regimen (once or twice daily) in the treatment of uncomplicated {P}. falciparum malaria, a multicentre clinical study was conducted. {M}ethods: {A} multicentre, randomized, controlled, investigator-blinded, parallel-group study was conducted in five {A}frican centers in {C}ameroon, {M}adagascar, {M}ali and {S}enegal from {M}arch to {D}ecember 2006. {E}fficacy and safety of {ASAQ} were assessed compared to those of artemether + lumefantrine ({AL}). {T}he {WHO} protocol with a 28-day follow-up for assessing the drug therapeutic efficacy was used. {P}atients suffering from uncomplicated {P}. falciparum malaria were randomized to receive {ASAQ} orally once daily ({ASAQ}1), {ASAQ} twice daily ({ASAQ}2) or {AL} twice daily ({AL}) for three days. {T}he primary outcome was {PCR}-corrected parasitological cure rate and clinical response. {R}esults: {O}f 941 patients initially randomized and stratified into two age groups (<5 years, and >= 5 years), 936 (99.5%) were retained for the intent to treat ({ITT}) analysis, and 859 (91.3%) patients for the per protocol ({PP}) analysis. {A}mong {ITT} population, up to {D}28, {PCR}-corrected adequate parasitological and clinical response rates were 95.2% in the {ASAQ}1 group, 94.9% in the {ASAQ}2 group and 95.5% in the {AL} group. {M}oreover, the cure rate evaluated among {PP} population was >= 98.5% in both {ASAQ} therapeutic arms. {T}herapeutic response rates did not display any significant differences between age groups or between one geographical site and another. {A}ltogether, this demonstrates the non-inferiority of {ASAQ}1 regimen compared to both {ASAQ}2 and {AL} regimens. {D}uring follow-up mild and moderate adverse events including gastrointestinal and/or nervous disorders were reported in 29.3% of patients, with no difference between groups in the nature, frequency or intensity of adverse events. {C}onclusion: {T}he non-inferiority of {ASAQ} compared with {AL} was demonstrated. {T}he fixed-dose combination artesunate + amodiaquine ({ASAQ}) is safe and efficacious even in young children under 5 years of age. {W}hilst administration on a twice-a-day basis does not improve the efficacy of {ASAQ} significantly, a once-a-day intake of this new combination clearly appears as an effective and safe therapy in the treatment of uncomplicated {P}. falciparum malaria both in adults and children. {I}mplications of such findings are of primary importance in terms of public health especially in {A}frican countries. {A}s most national policies plan to strengthen malaria control to reach the elimination of this disease, anti-malarial drugs such as the artesunate + amodiaquine fixed-dose {ACT} will play a pivotal role in this process.},
  keywords = {},
  booktitle = {},
  journal = {{M}alaria {J}ournal},
  volume = {8},
  numero = {},
  pages = {125},
  ISSN = {1475-2875},
  year = {2009},
  DOI = {10.1186/1475-2875-8-125},
  URL = {https://www.documentation.ird.fr/hor/fdi:010046164},
}