A multi-center, open-label trial to compare the efficacy and pharmacokinetics of Artemether-Lumefantrine in children with severe acute malnutrition versus children without severe acute malnutrition: study protocol for the MAL-NUT study

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dc.contributor.authorDenoeud-Ndam, Liseen_ZA
dc.contributor.authorDicko, Alassaneen_ZA
dc.contributor.authorBaudin, Elisabethen_ZA
dc.contributor.authorGuindo, Ousmaneen_ZA
dc.contributor.authorGrandesso, Francescoen_ZA
dc.contributor.authorSagara, Issakaen_ZA
dc.contributor.authorLasry, Estrellaen_ZA
dc.contributor.authorPalma, Pedroen_ZA
dc.contributor.authorParra, Angelesen_ZA
dc.contributor.authorStepniewska, Kasiaen_ZA
dc.contributor.authorDjimde, Abdoulayeen_ZA
dc.contributor.authorBarnes, Karenen_ZA
dc.contributor.authorDoumbo, Ogobaraen_ZA
dc.contributor.authorEtard, Jean-Francoisen_ZA
dc.date.accessioned2015-12-07T08:51:43Z
dc.date.available2015-12-07T08:51:43Z
dc.date.issued2015en_ZA
dc.description.abstractBACKGROUND:Malnutrition and malaria frequently coexist in sub-Saharan African countries. Studies on efficacy of antimalarial treatments usually follow the WHO standardized protocol in which severely malnourished children are systematically excluded.Few studies have assessed the efficacy of chloroquine, sulfadoxine-pyrimethamine and quinine in severe acute malnourished children. Overall, efficacy of these treatments appeared to be reduced, attributed to lower immunity and for some antimalarials altered pharmacokinetic profiles and lower drug concentrations. However, similar research on the efficacy and pharmacokinetic profiles of artemisinin-combination therapies (ACTs) and especially artemether-lumefantrine in malnourished children is currently lacking.The main objective of this study is to assess whether artemether-lumefantrine is less efficacious in children suffering from severe acute malnutrition (SAM) compared to non-SAM children, and if so, to what extent this can be attributed to a sub-optimal pharmacokinetic profile.METHODS/DESIGN:In two sites, Ouelessebougou, Mali and Maradi, Niger, children with uncomplicated microscopically-confirmed P. falciparum malaria aged between 6 and 59 months will be enrolled. Two non-SAM children will be enrolled after the enrolment of each SAM case. Children with severe manifestations of malaria or complications of acute malnutrition needing intensive treatment will be excluded.Treatment intakes will be supervised and children will be followed-up for 42 days, according to WHO guidance for surveillance of antimalarial drug efficacy. Polymerase Chain Reaction genotyping will be used to distinguish recrudescence from re-infection. SAM children will also benefit from the national nutritional rehabilitation program.Outcomes will be compared between the SAM and non-SAM populations. The primary outcome will be adequate clinical and parasitological response at day 28 after PCR correction, estimated by Kaplan-Meier analysis. To assess the pharmacokinetic profile of lumefantrine, a sparse sampling approach will be used with randomized allocation of sampling times (5 per child). A total of 180 SAM children and 360 non-SAM children will be recruited during the 2013 and 2014 malaria seasons.DISCUSSION:This study will provide important information that is currently lacking on the effect of SAM on therapeutic efficacy and pharmacokinetic profile of artemether-lumefantrine. If it shows lower therapeutic efficacy and decreased lumefantrine concentrations, it would inform dose optimization studies in SAM children.TRIAL REGISTRATION:ClinicalTrials.gov: NCT01958905en_ZA
dc.identifier.apacitationDenoeud-Ndam, L., Dicko, A., Baudin, E., Guindo, O., Grandesso, F., Sagara, I., ... Etard, J. (2015). A multi-center, open-label trial to compare the efficacy and pharmacokinetics of Artemether-Lumefantrine in children with severe acute malnutrition versus children without severe acute malnutrition: study protocol for the MAL-NUT study. <i>BMC Infectious Diseases</i>, http://hdl.handle.net/11427/15645en_ZA
dc.identifier.chicagocitationDenoeud-Ndam, Lise, Alassane Dicko, Elisabeth Baudin, Ousmane Guindo, Francesco Grandesso, Issaka Sagara, Estrella Lasry, et al "A multi-center, open-label trial to compare the efficacy and pharmacokinetics of Artemether-Lumefantrine in children with severe acute malnutrition versus children without severe acute malnutrition: study protocol for the MAL-NUT study." <i>BMC Infectious Diseases</i> (2015) http://hdl.handle.net/11427/15645en_ZA
dc.identifier.citationDenoeud-Ndam, L., Dicko, A., Baudin, E., Guindo, O., Grandesso, F., Sagara, I., ... & Etard, J. F. (2015). A multi-center, open-label trial to compare the efficacy and pharmacokinetics of Artemether-Lumefantrine in children with severe acute malnutrition versus children without severe acute malnutrition: study protocol for the MAL-NUT study. BMC infectious diseases, 15(1), 228.en_ZA
dc.identifier.ris TY - Journal Article AU - Denoeud-Ndam, Lise AU - Dicko, Alassane AU - Baudin, Elisabeth AU - Guindo, Ousmane AU - Grandesso, Francesco AU - Sagara, Issaka AU - Lasry, Estrella AU - Palma, Pedro AU - Parra, Angeles AU - Stepniewska, Kasia AU - Djimde, Abdoulaye AU - Barnes, Karen AU - Doumbo, Ogobara AU - Etard, Jean-Francois AB - BACKGROUND:Malnutrition and malaria frequently coexist in sub-Saharan African countries. Studies on efficacy of antimalarial treatments usually follow the WHO standardized protocol in which severely malnourished children are systematically excluded.Few studies have assessed the efficacy of chloroquine, sulfadoxine-pyrimethamine and quinine in severe acute malnourished children. Overall, efficacy of these treatments appeared to be reduced, attributed to lower immunity and for some antimalarials altered pharmacokinetic profiles and lower drug concentrations. However, similar research on the efficacy and pharmacokinetic profiles of artemisinin-combination therapies (ACTs) and especially artemether-lumefantrine in malnourished children is currently lacking.The main objective of this study is to assess whether artemether-lumefantrine is less efficacious in children suffering from severe acute malnutrition (SAM) compared to non-SAM children, and if so, to what extent this can be attributed to a sub-optimal pharmacokinetic profile.METHODS/DESIGN:In two sites, Ouelessebougou, Mali and Maradi, Niger, children with uncomplicated microscopically-confirmed P. falciparum malaria aged between 6 and 59 months will be enrolled. Two non-SAM children will be enrolled after the enrolment of each SAM case. Children with severe manifestations of malaria or complications of acute malnutrition needing intensive treatment will be excluded.Treatment intakes will be supervised and children will be followed-up for 42 days, according to WHO guidance for surveillance of antimalarial drug efficacy. Polymerase Chain Reaction genotyping will be used to distinguish recrudescence from re-infection. SAM children will also benefit from the national nutritional rehabilitation program.Outcomes will be compared between the SAM and non-SAM populations. The primary outcome will be adequate clinical and parasitological response at day 28 after PCR correction, estimated by Kaplan-Meier analysis. To assess the pharmacokinetic profile of lumefantrine, a sparse sampling approach will be used with randomized allocation of sampling times (5 per child). A total of 180 SAM children and 360 non-SAM children will be recruited during the 2013 and 2014 malaria seasons.DISCUSSION:This study will provide important information that is currently lacking on the effect of SAM on therapeutic efficacy and pharmacokinetic profile of artemether-lumefantrine. If it shows lower therapeutic efficacy and decreased lumefantrine concentrations, it would inform dose optimization studies in SAM children.TRIAL REGISTRATION:ClinicalTrials.gov: NCT01958905 DA - 2015 DB - OpenUCT DO - 10.1186/s12879-015-0963-3 DP - University of Cape Town J1 - BMC Infectious Diseases LK - https://open.uct.ac.za PB - University of Cape Town PY - 2015 T1 - A multi-center, open-label trial to compare the efficacy and pharmacokinetics of Artemether-Lumefantrine in children with severe acute malnutrition versus children without severe acute malnutrition: study protocol for the MAL-NUT study TI - A multi-center, open-label trial to compare the efficacy and pharmacokinetics of Artemether-Lumefantrine in children with severe acute malnutrition versus children without severe acute malnutrition: study protocol for the MAL-NUT study UR - http://hdl.handle.net/11427/15645 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/15645
dc.identifier.urihttp://dx.doi.org/10.1186/s12879-015-0963-3
dc.identifier.vancouvercitationDenoeud-Ndam L, Dicko A, Baudin E, Guindo O, Grandesso F, Sagara I, et al. A multi-center, open-label trial to compare the efficacy and pharmacokinetics of Artemether-Lumefantrine in children with severe acute malnutrition versus children without severe acute malnutrition: study protocol for the MAL-NUT study. BMC Infectious Diseases. 2015; http://hdl.handle.net/11427/15645.en_ZA
dc.language.isoengen_ZA
dc.publisherBioMed Central Ltden_ZA
dc.publisher.departmentDivision of Clinical Pharmacologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution Licenseen_ZA
dc.rights.holder2015 Denoeud-Ndam et al.en_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourceBMC Infectious Diseasesen_ZA
dc.source.urihttp://www.biomedcentral.com/bmcinfectdis/en_ZA
dc.subject.otherMalariaen_ZA
dc.subject.otherSevere acute malnutritionen_ZA
dc.subject.otherArtemether-lumefantrine fixed combinationen_ZA
dc.subject.otherPharmacokineticsen_ZA
dc.subject.otherEfficacyen_ZA
dc.subject.otherNigeren_ZA
dc.subject.otherMalien_ZA
dc.titleA multi-center, open-label trial to compare the efficacy and pharmacokinetics of Artemether-Lumefantrine in children with severe acute malnutrition versus children without severe acute malnutrition: study protocol for the MAL-NUT studyen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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