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Pyronaridine-artesunate granules versus artemether-lumefantrine crushed tablets in children with Plasmodium falciparum malaria: a randomized controlled trial

BACKGROUND: Children are most vulnerable to malaria. A pyronaridine-artesunate pediatric granule formulation is being developed for the treatment of uncomplicated Plasmodium falciparum malaria. METHODS: This phase III, multi-center, comparative, open-label, parallel-group, controlled clinical trial...

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Autores principales: Kayentao, Kassoum, Doumbo, Ogobara K, Pénali, Louis K, Offianan, André T, Bhatt, Kirana M, Kimani, Joshua, Tshefu, Antoinette K, Kokolomami, Jack HT, Ramharter, Michael, de Salazar, Pablo Martinez, Tiono, Alfred B, Ouédraogo, Alphonse, Bustos, Maria Dorina G, Quicho, Frederick, Borghini-Fuhrer, Isabelle, Duparc, Stephan, Shin, Chang-Sik, Fleckenstein, Lawrence
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3566922/
https://www.ncbi.nlm.nih.gov/pubmed/23113947
http://dx.doi.org/10.1186/1475-2875-11-364
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author Kayentao, Kassoum
Doumbo, Ogobara K
Pénali, Louis K
Offianan, André T
Bhatt, Kirana M
Kimani, Joshua
Tshefu, Antoinette K
Kokolomami, Jack HT
Ramharter, Michael
de Salazar, Pablo Martinez
Tiono, Alfred B
Ouédraogo, Alphonse
Bustos, Maria Dorina G
Quicho, Frederick
Borghini-Fuhrer, Isabelle
Duparc, Stephan
Shin, Chang-Sik
Fleckenstein, Lawrence
author_facet Kayentao, Kassoum
Doumbo, Ogobara K
Pénali, Louis K
Offianan, André T
Bhatt, Kirana M
Kimani, Joshua
Tshefu, Antoinette K
Kokolomami, Jack HT
Ramharter, Michael
de Salazar, Pablo Martinez
Tiono, Alfred B
Ouédraogo, Alphonse
Bustos, Maria Dorina G
Quicho, Frederick
Borghini-Fuhrer, Isabelle
Duparc, Stephan
Shin, Chang-Sik
Fleckenstein, Lawrence
author_sort Kayentao, Kassoum
collection PubMed
description BACKGROUND: Children are most vulnerable to malaria. A pyronaridine-artesunate pediatric granule formulation is being developed for the treatment of uncomplicated Plasmodium falciparum malaria. METHODS: This phase III, multi-center, comparative, open-label, parallel-group, controlled clinical trial included patients aged ≤12 years, bodyweight ≥5 to <25 kg, with a reported history of fever at inclusion or in the previous 24 h and microscopically-confirmed uncomplicated P. falciparum malaria. Patients were randomized (2:1) to pyronaridine-artesunate granules (60/20 mg) once daily or artemether-lumefantrine crushed tablets (20/120 mg) twice daily, both dosed by bodyweight, orally (liquid suspension) for three days. RESULTS: Of 535 patients randomized, 355 received pyronaridine-artesunate and 180 received artemether-lumefantrine. Day-28 adequate clinical and parasitological response (ACPR), corrected for re-infection using polymerase chain reaction (PCR) genotyping (per-protocol population) was 97.1% (329/339; 95% CI 94.6, 98.6) for pyronaridine-artesunate; 98.8% (165/167; 95% CI 95.7, 99.9) for artemether-lumefantrine. The primary endpoint was achieved: pyronaridine-artesunate PCR-corrected day-28 ACPR was statistically significantly >90% (P < .0001). Pyronaridine-artesunate was non-inferior to artemether-lumefantrine: treatment difference -1.8% (95% CI -4.3 to 1.6). The incidence of drug-related adverse events was 37.2% (132/355) with pyronaridine-artesunate, 44.4% (80/180) with artemether-lumefantrine. Clinical biochemistry results showed similar mean changes versus baseline in the two treatment groups. From day 3 until study completion, one patient in each treatment group had peak alanine aminotransferase (ALT) >3 times the upper limit of normal (ULN) and peak total bilirubin >2xULN (i.e. within the Hy’s law definition). CONCLUSIONS: The pyronaridine-artesunate pediatric granule formulation was efficacious and was non-inferior to artemether-lumefantrine. The adverse event profile was similar for the two comparators. Pyronaridine-artesunate should be considered for inclusion in paediatric malaria treatment programmes. TRIAL REGISTRATION: ClinicalTrials.gov: identifier NCT00541385
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spelling pubmed-35669222013-02-11 Pyronaridine-artesunate granules versus artemether-lumefantrine crushed tablets in children with Plasmodium falciparum malaria: a randomized controlled trial Kayentao, Kassoum Doumbo, Ogobara K Pénali, Louis K Offianan, André T Bhatt, Kirana M Kimani, Joshua Tshefu, Antoinette K Kokolomami, Jack HT Ramharter, Michael de Salazar, Pablo Martinez Tiono, Alfred B Ouédraogo, Alphonse Bustos, Maria Dorina G Quicho, Frederick Borghini-Fuhrer, Isabelle Duparc, Stephan Shin, Chang-Sik Fleckenstein, Lawrence Malar J Research BACKGROUND: Children are most vulnerable to malaria. A pyronaridine-artesunate pediatric granule formulation is being developed for the treatment of uncomplicated Plasmodium falciparum malaria. METHODS: This phase III, multi-center, comparative, open-label, parallel-group, controlled clinical trial included patients aged ≤12 years, bodyweight ≥5 to <25 kg, with a reported history of fever at inclusion or in the previous 24 h and microscopically-confirmed uncomplicated P. falciparum malaria. Patients were randomized (2:1) to pyronaridine-artesunate granules (60/20 mg) once daily or artemether-lumefantrine crushed tablets (20/120 mg) twice daily, both dosed by bodyweight, orally (liquid suspension) for three days. RESULTS: Of 535 patients randomized, 355 received pyronaridine-artesunate and 180 received artemether-lumefantrine. Day-28 adequate clinical and parasitological response (ACPR), corrected for re-infection using polymerase chain reaction (PCR) genotyping (per-protocol population) was 97.1% (329/339; 95% CI 94.6, 98.6) for pyronaridine-artesunate; 98.8% (165/167; 95% CI 95.7, 99.9) for artemether-lumefantrine. The primary endpoint was achieved: pyronaridine-artesunate PCR-corrected day-28 ACPR was statistically significantly >90% (P < .0001). Pyronaridine-artesunate was non-inferior to artemether-lumefantrine: treatment difference -1.8% (95% CI -4.3 to 1.6). The incidence of drug-related adverse events was 37.2% (132/355) with pyronaridine-artesunate, 44.4% (80/180) with artemether-lumefantrine. Clinical biochemistry results showed similar mean changes versus baseline in the two treatment groups. From day 3 until study completion, one patient in each treatment group had peak alanine aminotransferase (ALT) >3 times the upper limit of normal (ULN) and peak total bilirubin >2xULN (i.e. within the Hy’s law definition). CONCLUSIONS: The pyronaridine-artesunate pediatric granule formulation was efficacious and was non-inferior to artemether-lumefantrine. The adverse event profile was similar for the two comparators. Pyronaridine-artesunate should be considered for inclusion in paediatric malaria treatment programmes. TRIAL REGISTRATION: ClinicalTrials.gov: identifier NCT00541385 BioMed Central 2012-10-31 /pmc/articles/PMC3566922/ /pubmed/23113947 http://dx.doi.org/10.1186/1475-2875-11-364 Text en Copyright ©2012 Kayentao et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Kayentao, Kassoum
Doumbo, Ogobara K
Pénali, Louis K
Offianan, André T
Bhatt, Kirana M
Kimani, Joshua
Tshefu, Antoinette K
Kokolomami, Jack HT
Ramharter, Michael
de Salazar, Pablo Martinez
Tiono, Alfred B
Ouédraogo, Alphonse
Bustos, Maria Dorina G
Quicho, Frederick
Borghini-Fuhrer, Isabelle
Duparc, Stephan
Shin, Chang-Sik
Fleckenstein, Lawrence
Pyronaridine-artesunate granules versus artemether-lumefantrine crushed tablets in children with Plasmodium falciparum malaria: a randomized controlled trial
title Pyronaridine-artesunate granules versus artemether-lumefantrine crushed tablets in children with Plasmodium falciparum malaria: a randomized controlled trial
title_full Pyronaridine-artesunate granules versus artemether-lumefantrine crushed tablets in children with Plasmodium falciparum malaria: a randomized controlled trial
title_fullStr Pyronaridine-artesunate granules versus artemether-lumefantrine crushed tablets in children with Plasmodium falciparum malaria: a randomized controlled trial
title_full_unstemmed Pyronaridine-artesunate granules versus artemether-lumefantrine crushed tablets in children with Plasmodium falciparum malaria: a randomized controlled trial
title_short Pyronaridine-artesunate granules versus artemether-lumefantrine crushed tablets in children with Plasmodium falciparum malaria: a randomized controlled trial
title_sort pyronaridine-artesunate granules versus artemether-lumefantrine crushed tablets in children with plasmodium falciparum malaria: a randomized controlled trial
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3566922/
https://www.ncbi.nlm.nih.gov/pubmed/23113947
http://dx.doi.org/10.1186/1475-2875-11-364
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