Pyronaridine–Artesunate versus Mefloquine plus Artesunate for Malaria

Rueangweerayut, Ronnatrai; Phyo, Aung Pyae; Uthaisin, Chirapong; Yi, Poravuth; Bình, Trần Quang; Tinto, Halidou; Pénali, Louis K.; Valecha, Neena; Tien, Nong T; Abdulla, Salim; Borghini-Fuhrer, Isabelle; Duparc, Stephan; Shin, Chang-Sik; Fleckenstein, Lawrence

doi:10.1056/nejmoa1007125

Cited by 77 publications

(105 citation statements)

References 19 publications

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“…Most of the patients included in this study were adults with low-level parasitemia (Ͻ100,000 parasites/l); thus, failures were not associated with these known risk factors, i.e., young age and high parasite burden. The high day 42 recrudescence rate reported for Pailin is consistent with that noted in 2007 to 2008 for pyronaridine-artesunate at this site (10.2%) (20). In contrast, across other regions of Asia and Africa, Kaplan-Meier estimates of day 42 PCR-adjusted recrudescence rates in three phase 3 trials of pyronaridine-artesunate for treatment of falciparum malaria were 1.2%, 4.5%, and 5.0% (18,21).…”

Section: Discussionsupporting

confidence: 82%

“…In contrast, across other regions of Asia and Africa, Kaplan-Meier estimates of day 42 PCR-adjusted recrudescence rates in three phase 3 trials of pyronaridine-artesunate for treatment of falciparum malaria were 1.2%, 4.5%, and 5.0% (18,21). Pyronaridine-artesunate was well tolerated, with a safety profile consistent with those reported in previous studies (17,18,20,21,24). Pyronaridine-artesunate efficacy was numerically higher in Pursat than in Pailin, although this difference did not reach statistical significance.…”

Section: Discussionsupporting

confidence: 72%

“…In previous studies of pyronaridine-artesunate treatment of P. falciparum malaria, Ͼ96% of non-Cambodian patients had parasite clearance by day 3, versus 62.9% in Pailin (17,18,20,21). Similarly, the median parasite clearance times were 23.9 h in African countries, 23.8 h in India, 24.0 to 32.0 h in Vietnam, and 31.3 to 31.8 h in Thailand, versus 64.1 h in Pailin (17,18,20,21). In this study, only 86.7% of patients at Pursat and 56.4% at Pailin were aparasitic at 72 h, and the median parasite clearance time was 72 h at both sites, which is suggestive of artemisinin resistance.…”

Section: Discussionmentioning

confidence: 92%

“…Therefore, reduced susceptibility of P. falciparum to the pyronaridine component was present in western Cambodia, although confirmatory studies were necessary. Notably, the parasite clearance rate was significantly increased with both pyronaridine-artesunate and mefloquine-artesunate in Cambodia versus other countries, which is suggestive of artemisinin resistance (20).…”

mentioning

confidence: 92%

“…Across all the Asian and African countries included in phase 2/3 trials, pyronaridine-artesunate had high efficacy against P. falciparum malaria: the day 28 PCR-adjusted adequate clinical and parasitological response (ACPR) was 98.5% (per-protocol population), and the efficacy was similar to that of first-line ACTs (17)(18)(19)(20)(21). However, data from Pailin obtained in a phase 3 study of P. falciparum malaria conducted in 2007 to 2008 reported a day 42 recrudescence rate of 10.2% with pyronaridineartesunate (n ϭ 140), versus 0% for mefloquine-artesunate (n ϭ 71; P ϭ 0.04) (20). Therefore, reduced susceptibility of P. falciparum to the pyronaridine component was present in western Cambodia, although confirmatory studies were necessary.…”

mentioning

confidence: 99%

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Efficacy and Safety of Pyronaridine-Artesunate for Treatment of Uncomplicated Plasmodium falciparum Malaria in Western Cambodia

Leang

Canavati

Khim

et al. 2016

Antimicrob Agents Chemother

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Section: Discussionsupporting

confidence: 82%

Section: Discussionsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 92%

mentioning

confidence: 92%

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confidence: 99%

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Efficacy and Safety of Pyronaridine-Artesunate for Treatment of Uncomplicated Plasmodium falciparum Malaria in Western Cambodia

Leang

Canavati

Khim

et al. 2016

Antimicrob Agents Chemother

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Artesunate plus pyronaridine for treating uncomplicatedPlasmodium falciparummalaria

Bukirwa

Unnikrishnan

Kramer

et al. 2014

Cochrane Database of Systematic Reviews

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BackgroundThe World Health Organization (WHO) recommends that people with uncomplicated Plasmodium falciparum malaria are treated using Artemisinin-based Combination Therapy (ACT). ACT combines three-days of a short-acting artemisinin derivative with a longer-acting antimalarial which has a different mode of action. Pyronaridine has been reported as an effective antimalarial over two decades of use in parts of Asia, and is currently being evaluated as a partner drug for artesunate.ObjectivesTo evaluate the efficacy and safety of artesunate-pyronaridine compared to alternative ACTs for treating people with uncomplicated P. falciparum malaria.Search methodsWe searched the Cochrane Infectious Diseases Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library; MEDLINE; EMBASE; LILACS; ClinicalTrials.gov; the metaRegister of Controlled Trials (mRCT); and the WHO International Clinical Trials Search Portal up to 16 January 2014. We searched reference lists and conference abstracts, and contacted experts for information about ongoing and unpublished trials.Selection criteriaRandomized controlled trials of artesunate-pyronaridine versus other ACTs in adults and children with uncomplicated P. falciparum malaria.For the safety analysis, we also included adverse events data from trials comparing any treatment regimen containing pyronaridine with regimens not containing pyronaridine.Data collection and analysisTwo authors independently assessed trial eligibility and risk of bias, and extracted data. We combined dichotomous data using risk ratios (RR) and continuous data using mean differences (MD), and presented all results with a 95% confidence interval (CI). We used the GRADE approach to assess the quality of evidence.Main resultsWe included six randomized controlled trials enrolling 3718 children and adults.Artesunate-pyronaridine versus artemether-lumefantrineIn two multicentre trials, enrolling mainly older children and adults from west and south-central Africa, both artesunate-pyronaridine and artemether-lumefantrine had fewer than 5% PCR adjusted treatment failures during 42 days of follow-up, with no differences between groups (two trials, 1472 participants, low quality evidence). There were fewer new infections during the first 28 days in those given artesunate-pyronaridine (PCR-unadjusted treatment failure: RR 0.60, 95% CI 0.40 to 0.90, two trials, 1720 participants, moderate quality evidence), but no difference was detected over the whole 42 day follow-up (two trials, 1691 participants, moderate quality evidence).Artesunate-pyronaridine versus artesunate plus mefloquineIn one multicentre trial, enrolling mainly older children and adults from South East Asia, both artesunate-pyronaridine and artesunate plus mefloquine had fewer than 5% PCR adjusted treatment failures during 28 days follow-up (one trial, 1187 participants, moderate quality evidence). PCR-adjusted treatment failures were 6% by day 42 for these treated with artesunate-pyronaridine, and 4% f...

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Pyronaridine-artesunate for treating uncomplicated Plasmodium falciparum malaria

Pryce

Hine

2019

Cochrane Database of Systematic Reviews

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BackgroundThe World Health Organization (WHO) recommends artemisinin‐based combination therapies (ACTs) to treat uncomplicated Plasmodium falciparum (P falciparum) malaria. Concerns about artemisinin resistance have led to global initiatives to develop new partner drugs to protect artemisinin derivatives in ACT. Pyronaridine‐artesunate is a novel ACT.ObjectivesTo evaluate the efficacy of pyronaridine‐artesunate compared to alternative ACTs for treating people with uncomplicated P falciparum malaria, and to evaluate the safety of pyronaridine‐artesunate and other pyronaridine treatments compared to alternative treatments.Search methodsWe searched the Cochrane Infectious Diseases Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE; Embase; and LILACS. We also searched ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform Search Portal, and the International Standard Randomized Controlled Trial Number (ISRCTN) registry for ongoing or recently completed trials. The date of the last search was 8 May 2018.Selection criteriaEfficacy analysis: randomized controlled trials (RCTs) of pyronaridine‐artesunate for treating uncomplicated P falciparum malaria.Safety analysis: RCTs of pyronaridine‐artesunate or pyronaridine for treating P falciparum or P vivax malaria.Data collection and analysisFor this update, two review authors independently re‐extracted all data and assessed certainty of evidence. We meta‐analysed data to calculate risk ratios (RRs) for treatment failures between comparisons, and for safety outcomes between and across comparisons.Main resultsWe included 10 relevant studies. Seven studies were co‐funded by Shin Poong Pharmaceuticals which manufactures the drug. Three studies were funded by government agencies.For efficacy analysis we identified five RCTs with 5711 participants. This included 4465 participants from 13 sites in Africa, and 1246 participants from five sites in Asia. It included 541 children aged less than five years.For polymerase chain reaction (PCR)‐adjusted failures at day 28, pyronaridine‐artesunate may have fewer failures compared to artemether‐lumefantrine (RR 0.59, 95% confidence interval (CI) 0.26 to 1.31; 4 RCTs, 3068 participants, low‐certainty evidence), artesunate‐amodiaquine (RR 0.55, 95% CI 0.11 to 2.77; 1 RCT, 1245 participants, low‐certainty evidence), and mefloquine plus artesunate (RR 0.37, 95% CI 0.13 to 1.05; 1 RCT, 1117 participants, low‐certainty evidence).For unadjusted failures at day 28, pyronaridine‐artesunate may have fewer failures compared to artemether‐lumefantrine (RR 0.27, 95% CI 0.13 to 0.58; 4 RCTs, 3149 participants, low‐certainty evidence), and probably has fewer failures compared to artesunate‐amodiaquine (RR 0.49, 95% CI 0.30 to 0.81; 1 RCT, 1257 participants, moderate‐certainty evidence) and mefloquine plus artesunate (RR 0.36, 95% CI 0.17 to 0.78; 1 RCT, 1120 participants, moderate‐certainty evidence).For PCR‐adjusted failures at day 42, pyronaridine‐artesunat...

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Pyronaridine–Artesunate versus Mefloquine plus Artesunate for Malaria

Cited by 77 publications

References 19 publications

Efficacy and Safety of Pyronaridine-Artesunate for Treatment of Uncomplicated Plasmodium falciparum Malaria in Western Cambodia

Efficacy and Safety of Pyronaridine-Artesunate for Treatment of Uncomplicated Plasmodium falciparum Malaria in Western Cambodia

Artesunate plus pyronaridine for treating uncomplicatedPlasmodium falciparummalaria

Pyronaridine-artesunate for treating uncomplicated Plasmodium falciparum malaria

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