Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1782258623552946176 |
---|---|
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 |
format | Online Article Text |
id | pubmed-3566922 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT kayentaokassoum pyronaridineartesunategranulesversusartemetherlumefantrinecrushedtabletsinchildrenwithplasmodiumfalciparummalariaarandomizedcontrolledtrial AT doumboogobarak pyronaridineartesunategranulesversusartemetherlumefantrinecrushedtabletsinchildrenwithplasmodiumfalciparummalariaarandomizedcontrolledtrial AT penalilouisk pyronaridineartesunategranulesversusartemetherlumefantrinecrushedtabletsinchildrenwithplasmodiumfalciparummalariaarandomizedcontrolledtrial AT offiananandret pyronaridineartesunategranulesversusartemetherlumefantrinecrushedtabletsinchildrenwithplasmodiumfalciparummalariaarandomizedcontrolledtrial AT bhattkiranam pyronaridineartesunategranulesversusartemetherlumefantrinecrushedtabletsinchildrenwithplasmodiumfalciparummalariaarandomizedcontrolledtrial AT kimanijoshua pyronaridineartesunategranulesversusartemetherlumefantrinecrushedtabletsinchildrenwithplasmodiumfalciparummalariaarandomizedcontrolledtrial AT tshefuantoinettek pyronaridineartesunategranulesversusartemetherlumefantrinecrushedtabletsinchildrenwithplasmodiumfalciparummalariaarandomizedcontrolledtrial AT kokolomamijackht pyronaridineartesunategranulesversusartemetherlumefantrinecrushedtabletsinchildrenwithplasmodiumfalciparummalariaarandomizedcontrolledtrial AT ramhartermichael pyronaridineartesunategranulesversusartemetherlumefantrinecrushedtabletsinchildrenwithplasmodiumfalciparummalariaarandomizedcontrolledtrial AT desalazarpablomartinez pyronaridineartesunategranulesversusartemetherlumefantrinecrushedtabletsinchildrenwithplasmodiumfalciparummalariaarandomizedcontrolledtrial AT tionoalfredb pyronaridineartesunategranulesversusartemetherlumefantrinecrushedtabletsinchildrenwithplasmodiumfalciparummalariaarandomizedcontrolledtrial AT ouedraogoalphonse pyronaridineartesunategranulesversusartemetherlumefantrinecrushedtabletsinchildrenwithplasmodiumfalciparummalariaarandomizedcontrolledtrial AT bustosmariadorinag pyronaridineartesunategranulesversusartemetherlumefantrinecrushedtabletsinchildrenwithplasmodiumfalciparummalariaarandomizedcontrolledtrial AT quichofrederick pyronaridineartesunategranulesversusartemetherlumefantrinecrushedtabletsinchildrenwithplasmodiumfalciparummalariaarandomizedcontrolledtrial AT borghinifuhrerisabelle pyronaridineartesunategranulesversusartemetherlumefantrinecrushedtabletsinchildrenwithplasmodiumfalciparummalariaarandomizedcontrolledtrial AT duparcstephan pyronaridineartesunategranulesversusartemetherlumefantrinecrushedtabletsinchildrenwithplasmodiumfalciparummalariaarandomizedcontrolledtrial AT shinchangsik pyronaridineartesunategranulesversusartemetherlumefantrinecrushedtabletsinchildrenwithplasmodiumfalciparummalariaarandomizedcontrolledtrial AT fleckensteinlawrence pyronaridineartesunategranulesversusartemetherlumefantrinecrushedtabletsinchildrenwithplasmodiumfalciparummalariaarandomizedcontrolledtrial |