Efficacy of artesunate-amodiaquine and artemether-lumefantrine fixed-dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria among children aged six to 59 months in Nimba County, Liberia: an open-label randomized non-inferiority trial.
BACKGROUND: Prospective efficacy monitoring of anti-malarial treatments is imperative for timely detection of resistance development. The in vivo efficacy of artesunate-amodiaquine (ASAQ) fixed-dose combination (FDC) was compared to that of artemether-lumefantrine (AL) among children aged six to 59...
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
BioMed Central
2013
|
| _version_ | 1826295519870189568 |
|---|---|
| author | Schramm, B Valeh, P Baudin, E Mazinda, C Smith, R Pinoges, L Dhorda, M Boum, Y Sundaygar, T Zolia, Y Jones, J Comte, E Houzé, P Jullien, V Carn, G Kiechel, JR Ashley, E Guérin, P |
| author_facet | Schramm, B Valeh, P Baudin, E Mazinda, C Smith, R Pinoges, L Dhorda, M Boum, Y Sundaygar, T Zolia, Y Jones, J Comte, E Houzé, P Jullien, V Carn, G Kiechel, JR Ashley, E Guérin, P |
| author_sort | Schramm, B |
| collection | OXFORD |
| description | BACKGROUND: Prospective efficacy monitoring of anti-malarial treatments is imperative for timely detection of resistance development. The in vivo efficacy of artesunate-amodiaquine (ASAQ) fixed-dose combination (FDC) was compared to that of artemether-lumefantrine (AL) among children aged six to 59 months in Nimba County, Liberia, where Plasmodium falciparum malaria is endemic and efficacy data are scarce. METHODS: An open-label, randomized controlled non-inferiority trial compared the genotyping adjusted day 42 cure rates of ASAQ FDC (ASAQ Winthrop®) to AL (Coartem®) in 300 children aged six to 59 months with uncomplicated falciparum malaria. Inclusion was between December 2008 and May 2009. Randomization (1:1) was to a three-day observed oral regimen (ASAQ: once a day; AL: twice a day, given with fatty food). Day 7 desethylamodiaquine and lumefantrine blood-concentrations were also measured. RESULTS: The day 42 genotyping-adjusted cure rate estimates were 97.3% [95% CI: 91.6-99.1] for ASAQ and 94.2% [88.1-97.2] for AL (Kaplan-Meier survival estimates). The difference in day 42 cure rates was -3.1% [upper limit 95% CI: 1.2%]. These results were confirmed by observed proportion of patients cured at day 42 on the per-protocol population. Parasite clearance was 100% (ASAQ) and 99.3% (AL) on day 3. The probability to remain free of re-infection was 0.55 [95% CI: 0.46-0.63] (ASAQ) and 0.66 [0.57-0.73] (AL) (p = 0.017). CONCLUSIONS: Both ASAQ and AL were highly efficacious and ASAQ was non-inferior to AL. The proportion of patients with re-infection was high in both arms in this highly endemic setting. In 2010, ASAQ FDC was adopted as the first-line national treatment in Liberia. Continuous efficacy monitoring is recommended. TRIAL REGISTRATION: The protocols were registered with Current Controlled Trials, under the identifier numbers ISRCTN51688713, ISRCTN40020296. |
| first_indexed | 2024-03-07T04:02:18Z |
| format | Journal article |
| id | oxford-uuid:c4fe560c-3e77-43a5-a6f2-d5b97e73dc55 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:02:18Z |
| publishDate | 2013 |
| publisher | BioMed Central |
| record_format | dspace |
| spelling | oxford-uuid:c4fe560c-3e77-43a5-a6f2-d5b97e73dc552022-03-27T06:27:43ZEfficacy of artesunate-amodiaquine and artemether-lumefantrine fixed-dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria among children aged six to 59 months in Nimba County, Liberia: an open-label randomized non-inferiority trial.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c4fe560c-3e77-43a5-a6f2-d5b97e73dc55EnglishSymplectic Elements at OxfordBioMed Central2013Schramm, BValeh, PBaudin, EMazinda, CSmith, RPinoges, LDhorda, MBoum, YSundaygar, TZolia, YJones, JComte, EHouzé, PJullien, VCarn, GKiechel, JRAshley, EGuérin, P BACKGROUND: Prospective efficacy monitoring of anti-malarial treatments is imperative for timely detection of resistance development. The in vivo efficacy of artesunate-amodiaquine (ASAQ) fixed-dose combination (FDC) was compared to that of artemether-lumefantrine (AL) among children aged six to 59 months in Nimba County, Liberia, where Plasmodium falciparum malaria is endemic and efficacy data are scarce. METHODS: An open-label, randomized controlled non-inferiority trial compared the genotyping adjusted day 42 cure rates of ASAQ FDC (ASAQ Winthrop®) to AL (Coartem®) in 300 children aged six to 59 months with uncomplicated falciparum malaria. Inclusion was between December 2008 and May 2009. Randomization (1:1) was to a three-day observed oral regimen (ASAQ: once a day; AL: twice a day, given with fatty food). Day 7 desethylamodiaquine and lumefantrine blood-concentrations were also measured. RESULTS: The day 42 genotyping-adjusted cure rate estimates were 97.3% [95% CI: 91.6-99.1] for ASAQ and 94.2% [88.1-97.2] for AL (Kaplan-Meier survival estimates). The difference in day 42 cure rates was -3.1% [upper limit 95% CI: 1.2%]. These results were confirmed by observed proportion of patients cured at day 42 on the per-protocol population. Parasite clearance was 100% (ASAQ) and 99.3% (AL) on day 3. The probability to remain free of re-infection was 0.55 [95% CI: 0.46-0.63] (ASAQ) and 0.66 [0.57-0.73] (AL) (p = 0.017). CONCLUSIONS: Both ASAQ and AL were highly efficacious and ASAQ was non-inferior to AL. The proportion of patients with re-infection was high in both arms in this highly endemic setting. In 2010, ASAQ FDC was adopted as the first-line national treatment in Liberia. Continuous efficacy monitoring is recommended. TRIAL REGISTRATION: The protocols were registered with Current Controlled Trials, under the identifier numbers ISRCTN51688713, ISRCTN40020296. |
| spellingShingle | Schramm, B Valeh, P Baudin, E Mazinda, C Smith, R Pinoges, L Dhorda, M Boum, Y Sundaygar, T Zolia, Y Jones, J Comte, E Houzé, P Jullien, V Carn, G Kiechel, JR Ashley, E Guérin, P Efficacy of artesunate-amodiaquine and artemether-lumefantrine fixed-dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria among children aged six to 59 months in Nimba County, Liberia: an open-label randomized non-inferiority trial. |
| title | Efficacy of artesunate-amodiaquine and artemether-lumefantrine fixed-dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria among children aged six to 59 months in Nimba County, Liberia: an open-label randomized non-inferiority trial. |
| title_full | Efficacy of artesunate-amodiaquine and artemether-lumefantrine fixed-dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria among children aged six to 59 months in Nimba County, Liberia: an open-label randomized non-inferiority trial. |
| title_fullStr | Efficacy of artesunate-amodiaquine and artemether-lumefantrine fixed-dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria among children aged six to 59 months in Nimba County, Liberia: an open-label randomized non-inferiority trial. |
| title_full_unstemmed | Efficacy of artesunate-amodiaquine and artemether-lumefantrine fixed-dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria among children aged six to 59 months in Nimba County, Liberia: an open-label randomized non-inferiority trial. |
| title_short | Efficacy of artesunate-amodiaquine and artemether-lumefantrine fixed-dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria among children aged six to 59 months in Nimba County, Liberia: an open-label randomized non-inferiority trial. |
| title_sort | efficacy of artesunate amodiaquine and artemether lumefantrine fixed dose combinations for the treatment of uncomplicated plasmodium falciparum malaria among children aged six to 59 months in nimba county liberia an open label randomized non inferiority trial |
| work_keys_str_mv | AT schrammb efficacyofartesunateamodiaquineandartemetherlumefantrinefixeddosecombinationsforthetreatmentofuncomplicatedplasmodiumfalciparummalariaamongchildrenagedsixto59monthsinnimbacountyliberiaanopenlabelrandomizednoninferioritytrial AT valehp efficacyofartesunateamodiaquineandartemetherlumefantrinefixeddosecombinationsforthetreatmentofuncomplicatedplasmodiumfalciparummalariaamongchildrenagedsixto59monthsinnimbacountyliberiaanopenlabelrandomizednoninferioritytrial AT baudine efficacyofartesunateamodiaquineandartemetherlumefantrinefixeddosecombinationsforthetreatmentofuncomplicatedplasmodiumfalciparummalariaamongchildrenagedsixto59monthsinnimbacountyliberiaanopenlabelrandomizednoninferioritytrial AT mazindac efficacyofartesunateamodiaquineandartemetherlumefantrinefixeddosecombinationsforthetreatmentofuncomplicatedplasmodiumfalciparummalariaamongchildrenagedsixto59monthsinnimbacountyliberiaanopenlabelrandomizednoninferioritytrial AT smithr efficacyofartesunateamodiaquineandartemetherlumefantrinefixeddosecombinationsforthetreatmentofuncomplicatedplasmodiumfalciparummalariaamongchildrenagedsixto59monthsinnimbacountyliberiaanopenlabelrandomizednoninferioritytrial AT pinogesl efficacyofartesunateamodiaquineandartemetherlumefantrinefixeddosecombinationsforthetreatmentofuncomplicatedplasmodiumfalciparummalariaamongchildrenagedsixto59monthsinnimbacountyliberiaanopenlabelrandomizednoninferioritytrial AT dhordam efficacyofartesunateamodiaquineandartemetherlumefantrinefixeddosecombinationsforthetreatmentofuncomplicatedplasmodiumfalciparummalariaamongchildrenagedsixto59monthsinnimbacountyliberiaanopenlabelrandomizednoninferioritytrial AT boumy efficacyofartesunateamodiaquineandartemetherlumefantrinefixeddosecombinationsforthetreatmentofuncomplicatedplasmodiumfalciparummalariaamongchildrenagedsixto59monthsinnimbacountyliberiaanopenlabelrandomizednoninferioritytrial AT sundaygart efficacyofartesunateamodiaquineandartemetherlumefantrinefixeddosecombinationsforthetreatmentofuncomplicatedplasmodiumfalciparummalariaamongchildrenagedsixto59monthsinnimbacountyliberiaanopenlabelrandomizednoninferioritytrial AT zoliay efficacyofartesunateamodiaquineandartemetherlumefantrinefixeddosecombinationsforthetreatmentofuncomplicatedplasmodiumfalciparummalariaamongchildrenagedsixto59monthsinnimbacountyliberiaanopenlabelrandomizednoninferioritytrial AT jonesj efficacyofartesunateamodiaquineandartemetherlumefantrinefixeddosecombinationsforthetreatmentofuncomplicatedplasmodiumfalciparummalariaamongchildrenagedsixto59monthsinnimbacountyliberiaanopenlabelrandomizednoninferioritytrial AT comtee efficacyofartesunateamodiaquineandartemetherlumefantrinefixeddosecombinationsforthetreatmentofuncomplicatedplasmodiumfalciparummalariaamongchildrenagedsixto59monthsinnimbacountyliberiaanopenlabelrandomizednoninferioritytrial AT houzep efficacyofartesunateamodiaquineandartemetherlumefantrinefixeddosecombinationsforthetreatmentofuncomplicatedplasmodiumfalciparummalariaamongchildrenagedsixto59monthsinnimbacountyliberiaanopenlabelrandomizednoninferioritytrial AT jullienv efficacyofartesunateamodiaquineandartemetherlumefantrinefixeddosecombinationsforthetreatmentofuncomplicatedplasmodiumfalciparummalariaamongchildrenagedsixto59monthsinnimbacountyliberiaanopenlabelrandomizednoninferioritytrial AT carng efficacyofartesunateamodiaquineandartemetherlumefantrinefixeddosecombinationsforthetreatmentofuncomplicatedplasmodiumfalciparummalariaamongchildrenagedsixto59monthsinnimbacountyliberiaanopenlabelrandomizednoninferioritytrial AT kiecheljr efficacyofartesunateamodiaquineandartemetherlumefantrinefixeddosecombinationsforthetreatmentofuncomplicatedplasmodiumfalciparummalariaamongchildrenagedsixto59monthsinnimbacountyliberiaanopenlabelrandomizednoninferioritytrial AT ashleye efficacyofartesunateamodiaquineandartemetherlumefantrinefixeddosecombinationsforthetreatmentofuncomplicatedplasmodiumfalciparummalariaamongchildrenagedsixto59monthsinnimbacountyliberiaanopenlabelrandomizednoninferioritytrial AT guerinp efficacyofartesunateamodiaquineandartemetherlumefantrinefixeddosecombinationsforthetreatmentofuncomplicatedplasmodiumfalciparummalariaamongchildrenagedsixto59monthsinnimbacountyliberiaanopenlabelrandomizednoninferioritytrial |