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.author Denoeud-Ndam, Lise en_ZA
dc.contributor.author Dicko, Alassane en_ZA
dc.contributor.author Baudin, Elisabeth en_ZA
dc.contributor.author Guindo, Ousmane en_ZA
dc.contributor.author Grandesso, Francesco en_ZA
dc.contributor.author Sagara, Issaka en_ZA
dc.contributor.author Lasry, Estrella en_ZA
dc.contributor.author Palma, Pedro en_ZA
dc.contributor.author Parra, Angeles en_ZA
dc.contributor.author Stepniewska, Kasia en_ZA
dc.contributor.author Djimde, Abdoulaye en_ZA
dc.contributor.author Barnes, Karen en_ZA
dc.contributor.author Doumbo, Ogobara en_ZA
dc.contributor.author Etard, Jean-Francois en_ZA
dc.date.accessioned 2015-12-07T08:51:43Z
dc.date.available 2015-12-07T08:51:43Z
dc.date.issued 2015 en_ZA
dc.identifier.citation Denoeud-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.uri http://hdl.handle.net/11427/15645
dc.identifier.uri http://dx.doi.org/10.1186/s12879-015-0963-3
dc.description.abstract 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 en_ZA
dc.language.iso eng en_ZA
dc.publisher BioMed Central Ltd en_ZA
dc.rights This is an Open Access article distributed under the terms of the Creative Commons Attribution License en_ZA
dc.rights.uri http://creativecommons.org/licenses/by/4.0 en_ZA
dc.source BMC Infectious Diseases en_ZA
dc.source.uri http://www.biomedcentral.com/bmcinfectdis/ en_ZA
dc.subject.other Malaria en_ZA
dc.subject.other Severe acute malnutrition en_ZA
dc.subject.other Artemether-lumefantrine fixed combination en_ZA
dc.subject.other Pharmacokinetics en_ZA
dc.subject.other Efficacy en_ZA
dc.subject.other Niger en_ZA
dc.subject.other Mali en_ZA
dc.title 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 en_ZA
dc.type Journal Article en_ZA
dc.rights.holder 2015 Denoeud-Ndam et al. en_ZA
uct.type.publication Research en_ZA
uct.type.resource Article en_ZA
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Health Sciences en_ZA
dc.publisher.department Division of Clinical Pharmacology en_ZA
uct.type.filetype Text
uct.type.filetype Image
dc.identifier.apacitation Denoeud-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/11427/15645 en_ZA
dc.identifier.chicagocitation Denoeud-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/11427/15645 en_ZA
dc.identifier.vancouvercitation Denoeud-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.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


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