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

Malaria Journal

Research

Alphonse Ouédraogo¹  Alfred B Tiono¹  Antoinette K Tshefu²  Jack HT Kokolomami²  Ogobara K Doumbo³  Kassoum Kayentao³  André T Offianan⁴  Louis K Pénali⁴  Pablo Martinez de Salazar⁵  Michael Ramharter⁶  Isabelle Borghini-Fuhrer⁷  Stephan Duparc⁷  Frederick Quicho⁸  Maria Dorina G Bustos⁸  Chang-Sik Shin⁹  Joshua Kimani^1,10  Kirana M Bhatt^1,10  Lawrence Fleckenstein^1,11 

[1] Center National de Recherche et de Formation sur le Paludisme, Ministère de la Santé, Ouagadougou, Burkina Faso;Ecole de Santé Publique, Faculté de Médecine, Université de Kinshasa, Kinshasa, Democratic Republic of Congo;Faculté de Médecine de Pharmacie et d’Odonto-Stomatologie, Malaria Research and Training Center, Bamako, Mali;Malariology Department, Institut Pasteur, Abidjan, Côte d'Ivoire;Medical Research Unit, Albert Schweitzer Hospital, Lambaréné, Gabon;Institute of Tropical Medicine, Tübingen, Germany;Medical Research Unit, Albert Schweitzer Hospital, Lambaréné, Gabon;Institute of Tropical Medicine, Tübingen, Germany;Department of Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Vienna, Austria;Medicines for Malaria Venture, International Center Cointrin, PO Box 1826, Route de Pré-Bois 20, CH-1215, Geneva 15, Switzerland;Research Institute for Tropical Medicine, Department of Health, FICC, Alabang, Muntinlupa City, Metro Manila, Philippines;Shin Poong Pharmaceutical, Seoul, South Korea;UNITID, College of Health Sciences, University of Nairobi, Nairobi, Kenya;University of Iowa, Iowa City, IA, USA;

关键词: Pyronaridine-artesunate;    Artemether-lumefantrine;    Malaria;    Plasmodium falciparum;    Pediatric;   

DOI  :  10.1186/1475-2875-11-364

 received in 2012-08-13, accepted in 2012-10-18,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundChildren are most vulnerable to malaria. A pyronaridine-artesunate pediatric granule formulation is being developed for the treatment of uncomplicated Plasmodium falciparum malaria.MethodsThis 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.ResultsOf 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).ConclusionsThe 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 registrationClinicalTrials.gov: identifier NCT00541385

【 授权许可】

Unknown   
© Kayentao et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. 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.