Document Detail


Pyronaridine-artesunate versus mefloquine plus artesunate for malaria.
MedLine Citation:
PMID:  22475593     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Pyronaridine-artesunate is an artemisinin-based combination therapy under evaluation for the treatment of Plasmodium falciparum and P. vivax malaria.
METHODS: We conducted a phase 3, open-label, multicenter, noninferiority trial that included 1271 patients between 3 and 60 years of age from Asia (81.3%) or Africa (18.7%) with microscopically confirmed, uncomplicated P. falciparum malaria. Patients underwent randomization for treatment with a fixed-dose combination of 180 mg of pyronaridine and 60 mg of artesunate or with 250 mg of mefloquine plus 100 mg of artesunate. Doses were calculated according to body weight and administered once daily for 3 days.
RESULTS: Pyronaridine-artesunate was noninferior to mefloquine plus artesunate for the primary outcome: adequate clinical and parasitologic response in the per-protocol population on day 28, corrected for reinfection with the use of polymerase-chain-reaction (PCR) genotyping. For this outcome, efficacy in the group receiving pyronaridine-artesunate was 99.2% (743 of 749 patients; 95% confidence interval [CI], 98.3 to 99.7) and that in the group receiving mefloquine plus artesunate was 97.8% (360 of 368 patients; 95% CI, 95.8 to 99.1), with a treatment difference of 1.4 percentage points (95% CI, 0.0 to 3.5; P=0.05). In the intention-to-treat population, efficacy on day 42 in the group receiving pyronaridine-artesunate was 83.1% (705 of 848 patients; 95% CI, 80.4 to 85.6) and that in the group receiving mefloquine plus artesunate was 83.9% (355 of 423 patients; 95% CI, 80.1 to 87.3). In Cambodia, where there were 211 study patients, the median parasite clearance time was prolonged for both treatments: 64 hours versus 16.0 to 38.9 hours in other countries (P<0.001, on the basis of Kaplan-Meier estimates). Kaplan-Meier estimates of the recrudescence rate in the intention-to-treat population in Cambodia until day 42 were higher with pyronaridine-artesunate than with mefloquine plus artesunate (10.2% [95% CI, 5.4 to 18.6] vs. 0%; P=0.04 as calculated with the log-rank test), but similar for the other countries combined (4.7% [95% CI, 3.3 to 6.7] and 2.8% [95% CI, 1.5 to 5.3], respectively; P=0.24). Elevated levels of aminotransferases were observed in those receiving pyronaridine-artesunate. Two patients receiving mefloquine plus artesunate had seizures.
CONCLUSIONS: Fixed-dose pyronaridine-artesunate was efficacious in the treatment of uncomplicated P. falciparum malaria. In Cambodia, extended parasite clearance times were suggestive of in vivo resistance to artemisinin. (Funded by Shin Poong Pharmaceutical Company and the Medicines for Malaria Venture; ClinicalTrials.gov number, NCT00403260.).
Authors:
Ronnatrai Rueangweerayut; Aung Pyae Phyo; Chirapong Uthaisin; Yi Poravuth; Tran Quang Binh; Halidou Tinto; Louis K Pénali; Neena Valecha; Nong Thi Tien; Salim Abdulla; Isabelle Borghini-Fuhrer; Stephan Duparc; Chang-Sik Shin; Lawrence Fleckenstein;
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Publication Detail:
Type:  Clinical Trial, Phase III; Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The New England journal of medicine     Volume:  366     ISSN:  1533-4406     ISO Abbreviation:  N. Engl. J. Med.     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-04-05     Completed Date:  2012-04-12     Revised Date:  2014-02-24    
Medline Journal Info:
Nlm Unique ID:  0255562     Medline TA:  N Engl J Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1298-309     Citation Subset:  AIM; IM    
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00403260
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Africa
Antimalarials / administration & dosage,  adverse effects,  therapeutic use*
Artemisinins / administration & dosage,  adverse effects,  therapeutic use*
Asia
Child
Child, Preschool
Drug Combinations
Drug Resistance
Female
Humans
Intention to Treat Analysis
Kaplan-Meier Estimate
Malaria, Falciparum / drug therapy*
Male
Mefloquine / administration & dosage,  adverse effects,  therapeutic use*
Middle Aged
Naphthyridines / administration & dosage,  adverse effects,  therapeutic use*
Proportional Hazards Models
Young Adult
Grant Support
ID/Acronym/Agency:
089275//Wellcome Trust
Chemical
Reg. No./Substance:
0/Antimalarials; 0/Artemisinins; 0/Drug Combinations; 0/Naphthyridines; 74847-35-1/pyronaridine; 83507-69-1/artesunate; TML814419R/Mefloquine
Investigator
Investigator/Affiliation:
Kulya Rueangweerayut / ; Patima Sila / ; Duong Socheat / ; Meng Huot / ; Le Quoc Hung / ; Robert T Guiguemdé / ; Augustin Zeba / ; Touré A Offianan / ; B H Krishnamoorthy Rao / ; Susanta K Ghosh / ; Ngo Viet Thanh / ; Vera Juma /

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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