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
Abstract
Abstract
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
Publisher
Springer Science and Business Media LLC
Subject
Infectious Diseases,Parasitology
Reference24 articles.
1. Roll Back Malaria Partnership Secretariat: World malaria Day. 2010, Africa Update. http://www.rollbackmalaria.org/ProgressImpactSeries/docs/wmd2010report-en.pdf.
2. World Health Organization: World malaria report. 2011, http://www.who.int/malaria/world_malaria_report_2011/9789241564403_eng.pdf.
3. World Health Organization: Guidelines for the treatment of malaria. http://whqlibdoc.who.int/publications/2010/9789241547925_eng.pdf., second
4. World Health Organization: WHO list of prequalified medicinal products. http://apps.who.int/prequal/query/ProductRegistry.aspx?list=ma.
5. Tshefu AK, Gaye O, Kayentao K, Thompson R, Bhatt KM, Sesay SS, Bustos DG, Tjitra E, Bedu-Addo G, Borghini-Fuhrer I, Duparc S, Shin CS, Fleckenstein L: Efficacy and safety of a fixed-dose oral combination of pyronaridine-artesunate compared with artemether-lumefantrine in children and adults with uncomplicated Plasmodium falciparum malaria: a randomised non-inferiority trial. Lancet. 2010, 375: 1457-1467. 10.1016/S0140-6736(10)60322-4.
Cited by
41 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献