Tolerability and safety of artesunate-amodiaquine and artemether-lumefantrine fixed dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria: two open-label, randomized trials in Nimba County, Liberia.
<p>Background: Safety surveillance of widely used artemisinin-based combination therapy (ACT) is essential, but tolerability data in the over five years age group are largely anecdotal.</p> <p>Methods: Two open-label, randomized trials were conducted in Nimba County, Liberia: i) th...
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
BioMed Central
2013
|
| _version_ | 1797051713822130176 |
|---|---|
| author | Schramm, B Valeh, P Baudin, E Mazinda, C Smith, R Pinoges, L Sundaygar, T Zolia, Y Jones, J Comte, E Bruneel, A Branger, M Jullien, V Carn, G Kiechel, JR Ashley, E Guérin, P |
| author_facet | Schramm, B Valeh, P Baudin, E Mazinda, C Smith, R Pinoges, L Sundaygar, T Zolia, Y Jones, J Comte, E Bruneel, A Branger, M Jullien, V Carn, G Kiechel, JR Ashley, E Guérin, P |
| author_sort | Schramm, B |
| collection | OXFORD |
| description | <p>Background: Safety surveillance of widely used artemisinin-based combination therapy (ACT) is essential, but tolerability data in the over five years age group are largely anecdotal.</p> <p>Methods: Two open-label, randomized trials were conducted in Nimba County, Liberia: i) the main tolerability trial with 1,000 Plasmodium falciparum malaria patients aged over five years (Study-T), and, ii) an efficacy trial with a secondary objective of collecting tolerability data among 300 children age six to 59 months (Study-E). In both studies patients were randomized to fixed-dose artesunate-amodiaquine (ASAQ Winthrop®) or artemether-lumefantrine (AL, Coartem®), respectively. Clinical- and laboratory-adverse events (AEs) were recorded until day 28.</p> <p>Results: Study-T: most patients experienced at least one AE. Severe AEs were few, primarily asymptomatic blood system disorders or increased liver enzyme values. No treatment or study discontinuation occurred. Mild or moderate fatigue (39.8% vs 16.3%, p < 0.001), vomiting (7.1% vs 1.6%, p < 0.001), nausea (3.2% vs 1.0%, p = 0.01), and anaemia (14.9% vs 9.8%, p = 0.01) were more frequently recorded in the ASAQ versus AL arm. Study-E: mild or moderate AEs were common, including anaemia, fatigue, vomiting or diarrhoea. The few severe events were asymptomatic blood system disorders and four clinical events (pneumonia, malaria, vomiting and stomatitis).</p> <p>Conclusion: Both ASAQ and AL were well tolerated in patients of all age groups. No unexpected AEs occurred. Certain mild or moderate AEs were more frequent in the ASAQ arm. Standardised safety surveillance should continue for all forms of ACT.</p> <p>Trial registration: The protocols were registered with Current Controlled Trials, under the identifier numbers ISRCTN40020296, ISRCTN51688713, (http://www.controlled-trials.com).</p> |
| first_indexed | 2024-03-06T18:23:23Z |
| format | Journal article |
| id | oxford-uuid:071456f7-cb0c-486e-9eb2-4b5a7102acc0 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:23:23Z |
| publishDate | 2013 |
| publisher | BioMed Central |
| record_format | dspace |
| spelling | oxford-uuid:071456f7-cb0c-486e-9eb2-4b5a7102acc02022-03-26T09:05:50ZTolerability and safety of artesunate-amodiaquine and artemether-lumefantrine fixed dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria: two open-label, randomized trials in Nimba County, Liberia.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:071456f7-cb0c-486e-9eb2-4b5a7102acc0EnglishSymplectic Elements at OxfordBioMed Central2013Schramm, BValeh, PBaudin, EMazinda, CSmith, RPinoges, LSundaygar, TZolia, YJones, JComte, EBruneel, ABranger, MJullien, VCarn, GKiechel, JRAshley, EGuérin, P<p>Background: Safety surveillance of widely used artemisinin-based combination therapy (ACT) is essential, but tolerability data in the over five years age group are largely anecdotal.</p> <p>Methods: Two open-label, randomized trials were conducted in Nimba County, Liberia: i) the main tolerability trial with 1,000 Plasmodium falciparum malaria patients aged over five years (Study-T), and, ii) an efficacy trial with a secondary objective of collecting tolerability data among 300 children age six to 59 months (Study-E). In both studies patients were randomized to fixed-dose artesunate-amodiaquine (ASAQ Winthrop®) or artemether-lumefantrine (AL, Coartem®), respectively. Clinical- and laboratory-adverse events (AEs) were recorded until day 28.</p> <p>Results: Study-T: most patients experienced at least one AE. Severe AEs were few, primarily asymptomatic blood system disorders or increased liver enzyme values. No treatment or study discontinuation occurred. Mild or moderate fatigue (39.8% vs 16.3%, p < 0.001), vomiting (7.1% vs 1.6%, p < 0.001), nausea (3.2% vs 1.0%, p = 0.01), and anaemia (14.9% vs 9.8%, p = 0.01) were more frequently recorded in the ASAQ versus AL arm. Study-E: mild or moderate AEs were common, including anaemia, fatigue, vomiting or diarrhoea. The few severe events were asymptomatic blood system disorders and four clinical events (pneumonia, malaria, vomiting and stomatitis).</p> <p>Conclusion: Both ASAQ and AL were well tolerated in patients of all age groups. No unexpected AEs occurred. Certain mild or moderate AEs were more frequent in the ASAQ arm. Standardised safety surveillance should continue for all forms of ACT.</p> <p>Trial registration: The protocols were registered with Current Controlled Trials, under the identifier numbers ISRCTN40020296, ISRCTN51688713, (http://www.controlled-trials.com).</p> |
| spellingShingle | Schramm, B Valeh, P Baudin, E Mazinda, C Smith, R Pinoges, L Sundaygar, T Zolia, Y Jones, J Comte, E Bruneel, A Branger, M Jullien, V Carn, G Kiechel, JR Ashley, E Guérin, P Tolerability and safety of artesunate-amodiaquine and artemether-lumefantrine fixed dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria: two open-label, randomized trials in Nimba County, Liberia. |
| title | Tolerability and safety of artesunate-amodiaquine and artemether-lumefantrine fixed dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria: two open-label, randomized trials in Nimba County, Liberia. |
| title_full | Tolerability and safety of artesunate-amodiaquine and artemether-lumefantrine fixed dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria: two open-label, randomized trials in Nimba County, Liberia. |
| title_fullStr | Tolerability and safety of artesunate-amodiaquine and artemether-lumefantrine fixed dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria: two open-label, randomized trials in Nimba County, Liberia. |
| title_full_unstemmed | Tolerability and safety of artesunate-amodiaquine and artemether-lumefantrine fixed dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria: two open-label, randomized trials in Nimba County, Liberia. |
| title_short | Tolerability and safety of artesunate-amodiaquine and artemether-lumefantrine fixed dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria: two open-label, randomized trials in Nimba County, Liberia. |
| title_sort | tolerability and safety of artesunate amodiaquine and artemether lumefantrine fixed dose combinations for the treatment of uncomplicated plasmodium falciparum malaria two open label randomized trials in nimba county liberia |
| work_keys_str_mv | AT schrammb tolerabilityandsafetyofartesunateamodiaquineandartemetherlumefantrinefixeddosecombinationsforthetreatmentofuncomplicatedplasmodiumfalciparummalariatwoopenlabelrandomizedtrialsinnimbacountyliberia AT valehp tolerabilityandsafetyofartesunateamodiaquineandartemetherlumefantrinefixeddosecombinationsforthetreatmentofuncomplicatedplasmodiumfalciparummalariatwoopenlabelrandomizedtrialsinnimbacountyliberia AT baudine tolerabilityandsafetyofartesunateamodiaquineandartemetherlumefantrinefixeddosecombinationsforthetreatmentofuncomplicatedplasmodiumfalciparummalariatwoopenlabelrandomizedtrialsinnimbacountyliberia AT mazindac tolerabilityandsafetyofartesunateamodiaquineandartemetherlumefantrinefixeddosecombinationsforthetreatmentofuncomplicatedplasmodiumfalciparummalariatwoopenlabelrandomizedtrialsinnimbacountyliberia AT smithr tolerabilityandsafetyofartesunateamodiaquineandartemetherlumefantrinefixeddosecombinationsforthetreatmentofuncomplicatedplasmodiumfalciparummalariatwoopenlabelrandomizedtrialsinnimbacountyliberia AT pinogesl tolerabilityandsafetyofartesunateamodiaquineandartemetherlumefantrinefixeddosecombinationsforthetreatmentofuncomplicatedplasmodiumfalciparummalariatwoopenlabelrandomizedtrialsinnimbacountyliberia AT sundaygart tolerabilityandsafetyofartesunateamodiaquineandartemetherlumefantrinefixeddosecombinationsforthetreatmentofuncomplicatedplasmodiumfalciparummalariatwoopenlabelrandomizedtrialsinnimbacountyliberia AT zoliay tolerabilityandsafetyofartesunateamodiaquineandartemetherlumefantrinefixeddosecombinationsforthetreatmentofuncomplicatedplasmodiumfalciparummalariatwoopenlabelrandomizedtrialsinnimbacountyliberia AT jonesj tolerabilityandsafetyofartesunateamodiaquineandartemetherlumefantrinefixeddosecombinationsforthetreatmentofuncomplicatedplasmodiumfalciparummalariatwoopenlabelrandomizedtrialsinnimbacountyliberia AT comtee tolerabilityandsafetyofartesunateamodiaquineandartemetherlumefantrinefixeddosecombinationsforthetreatmentofuncomplicatedplasmodiumfalciparummalariatwoopenlabelrandomizedtrialsinnimbacountyliberia AT bruneela tolerabilityandsafetyofartesunateamodiaquineandartemetherlumefantrinefixeddosecombinationsforthetreatmentofuncomplicatedplasmodiumfalciparummalariatwoopenlabelrandomizedtrialsinnimbacountyliberia AT brangerm tolerabilityandsafetyofartesunateamodiaquineandartemetherlumefantrinefixeddosecombinationsforthetreatmentofuncomplicatedplasmodiumfalciparummalariatwoopenlabelrandomizedtrialsinnimbacountyliberia AT jullienv tolerabilityandsafetyofartesunateamodiaquineandartemetherlumefantrinefixeddosecombinationsforthetreatmentofuncomplicatedplasmodiumfalciparummalariatwoopenlabelrandomizedtrialsinnimbacountyliberia AT carng tolerabilityandsafetyofartesunateamodiaquineandartemetherlumefantrinefixeddosecombinationsforthetreatmentofuncomplicatedplasmodiumfalciparummalariatwoopenlabelrandomizedtrialsinnimbacountyliberia AT kiecheljr tolerabilityandsafetyofartesunateamodiaquineandartemetherlumefantrinefixeddosecombinationsforthetreatmentofuncomplicatedplasmodiumfalciparummalariatwoopenlabelrandomizedtrialsinnimbacountyliberia AT ashleye tolerabilityandsafetyofartesunateamodiaquineandartemetherlumefantrinefixeddosecombinationsforthetreatmentofuncomplicatedplasmodiumfalciparummalariatwoopenlabelrandomizedtrialsinnimbacountyliberia AT guerinp tolerabilityandsafetyofartesunateamodiaquineandartemetherlumefantrinefixeddosecombinationsforthetreatmentofuncomplicatedplasmodiumfalciparummalariatwoopenlabelrandomizedtrialsinnimbacountyliberia |