Pyronaridine-artesunate for treating uncomplicated Plasmodium falciparum malaria

Joseph Pryce, Melissa Taylor, Tilly Fox, Paul Hine, Joseph Pryce, Melissa Taylor, Tilly Fox, Paul Hine

Abstract

Background: The World Health Organization (WHO) recommends artemisinin-based combination therapies (ACTs) to treat uncomplicated Plasmodium 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.

Objectives: To 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 methods: We 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, and the ISRCTN registry for ongoing or recently completed trials. The date of the last search was 27 October 2021.

Selection criteria: For the efficacy analysis, we included randomized controlled trials (RCTs) of pyronaridine-artesunate for treating uncomplicated P falciparum malaria. For the safety analysis, we included RCTs that used pyronaridine alone or in combination with any other antimalarials. In addition to these analyses, we conducted a separate systematic review summarizing data on safety from non-randomized studies (NRS) of any patient receiving pyronaridine (NRS safety review). DATA COLLECTION AND ANALYSIS: Two review authors independently extracted all data and assessed the certainty of the evidence. We meta-analysed data to calculate risk ratios (RRs) for treatment failures between comparisons, and for safety outcomes between and across comparisons.

Main results: We included 10 relevant RCTs. Seven RCTs were co-funded by Shin Poong Pharmaceuticals, and three were funded by government agencies. Efficacy analysis (RCTs) For the efficacy analysis, we identified five RCTs comprising 5711 participants. This included 4465 participants from 13 sites in Africa, and 1246 participants from five sites in Asia. The analysis included 541 children aged less than five years. Overall, pyronaridine-artesunate had a polymerase chain reaction (PCR)-adjusted treatment failure rate of less than 5%. We evaluated pyronaridine-artesunate versus the following. • Artemether-lumefantrine. Pyronaridine artesunate may perform better for PCR-adjusted failures at day 28 (RR 0.59, 95% confidence interval (CI) 0.26 to 1.31; 4 RCTs, 3068 participants, low-certainty evidence); for unadjusted failures at day 28 (RR 0.27, 95% CI 0.13 to 0.58; 4 RCTs, 3149 participants, low-certainty evidence); and for unadjusted failures at day 42 (RR 0.61, 95% CI 0.46 to 0.82; 4 RCTs, 3080 participants, low-certainty evidence). For PCR-adjusted failures at day 42, there may be little or no difference between groups (RR 0.86, 95% CI 0.49 to 1.51; 4 RCTs, 2575 participants, low-certainty evidence). • Artesunate-amodiaquine. Pyronaridine artesunate may perform better for PCR-adjusted failures at day 28 (RR 0.55, 95% CI 0.11 to 2.77; 1 RCT, 1245 participants, low-certainty evidence); probably performs better for unadjusted failures at day 28 (RR 0.49, 95% CI 0.30 to 0.81; 1 RCT, 1257 participants, moderate-certainty evidence); may make little or no difference for PCR-adjusted failures at day 42 (RR 0.98, 95% CI 0.20 to 4.83; 1 RCT, 1091 participants, low-certainty evidence); and probably makes little or no difference for unadjusted failures at day 42 (RR 0.98, 95% CI 0.78 to 1.23; 1 RCT, 1235 participants, moderate-certainty evidence). • Mefloquine plus artesunate. Pyronaridine artesunate may perform better for PCR-adjusted failures at day 28 (RR 0.37, 95% CI 0.13 to 1.05; 1 RCT, 1117 participants, low-certainty evidence); probably performs better for unadjusted failures at day 28 (RR 0.36, 95% CI 0.17 to 0.78; 1 RCT, 1120 participants, moderate-certainty evidence); may make little or no difference for unadjusted failures at day 42 (RR 0.84, 95% CI 0.54 to 1.31; 1 RCT, 1059 participants, low-certainty evidence); but may lead to higher PCR-adjusted failures at day 42 (RR 1.80, 95% CI 0.90 to 3.57; 1 RCT, 1037 participants, low-certainty evidence). Safety analysis (RCTs) For the RCT safety analysis, we identified eight RCTs, one of which was delineated by study site, comparing pyronaridine-artesunate to other antimalarials. Pyronaridine-artesunate was associated with raised liver enzymes compared to other antimalarials: alanine aminotransferase (ALT) (RR 3.59, 95% CI 1.76 to 7.33; 8 RCTS, 6669 participants, high-certainty evidence) and aspartate transaminase (AST) (RR 2.22, 95% CI 1.12 to 4.41; 8 RCTs, 6669 participants, moderate-certainty evidence). No such effect was demonstrated with bilirubin (RR 1.03, 95% CI 0.49 to 2.18; 7 RCTs, 6384 participants, moderate-certainty evidence). There was one reported case in which raised ALT occurred with raised bilirubin. No study reported severe drug-induced liver injury. Electrocardiograph (ECG) abnormalities were less common with pyronaridine-artesunate compared to other antimalarials. We identified no other safety concerns. NRS safety review A review on safety in NRS allowed us to increase the population within which safety was assessed. We included seven studies with 9546 participants: five single-arm observational studies, one cohort event monitoring study, and one dose-escalation study. All studies provided data on adverse event frequency, with a small number of participants experiencing serious adverse events and adverse effects related to pyronaridine: serious adverse events average 0.37%; drug-related 9.0%. In two studies reporting elevations in liver enzymes, small percentages of participants (2.4% and 14.1% respectively) experienced increases in either ALT, AST, or bilirubin on day 7; however, these were small increases that returned to normal by day 42. AUTHORS' CONCLUSIONS: Pyronaridine-artesunate was efficacious against uncomplicated P falciparum malaria; achieved a PCR-adjusted treatment failure rate of less than 5% at days 28 and 42; and may be at least as good as, or better than, other marketed ACTs. Pyronaridine-artesunate increases the risk of episodes of abnormally raised ALT. The observational data did not signal an excess of clinically important adverse effects.

Trial registration: ClinicalTrials.gov NCT00422084.

Conflict of interest statement

JP is a CIDG Editor, and was not involved in the editorial process of this review update. He has no known conflicts of interest.

MT has no known conflicts of interest.

TF has no known conflicts of interest.

PH is a CIDG Editor, and was not involved in the editorial process of this review update. He was previously employed full time by Cochrane Infectious Diseases Group (CIDG), and currently works full time within the UK National Health Service (NHS). To the best of his knowledge, no financial or non‐financial conflicts of interests have influenced the current submitted work.

Copyright © 2022 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.

Figures

1
1
Study flow diagram.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Forest plot of comparison 1: Pyronaridine‐artesunate versus artemether‐lumefantrine, outcome 1.8: ALT increase > 5 × ULN, first treatment.
4
4
Forest plot of comparison 1: Pyronaridine‐artesunate versus artemether‐lumefantrine, outcome: 1.9 AST increase > 5 × ULN, first treatment.
5
5
Forest plot of comparison 4: Pyronaridine‐artesunate versus other antimalarials, outcome: 4.3 ALT increase > 5 × ULN, first treatment.
6
6
A comparison of adverse events following treatment with pyronaridine‐artesunate versus other antimalarials, based on the reporting guidelines in PRISMA harms (Zorzela 2016). Adverse events are categorized according to MedDRA system organ class and high level terms (MedDRA 2016). Where specific low level terms were reported, we have used footnotes to indicate the condition described. Where trials reported more than one low level term belonging to the same high level term, we have reported the low level term with the highest frequency.
aIncludes basophilia and monocytosis.
bAsymptomatic unifocal ventricular ectopics.
cIncludes dizziness and palpitations.
dEar pain.
e"Chills".
fInfluenza‐like illness.
gChest pain.
hProlonged QTc, t wave inversion.
iElevated creatine phosphokinase.
jWeight decreased.
kThrombocytopenia.
lHypoalbuminaemia.
mRaised creatinine.
nNeck pain.
oThroat pain, cold, postnasal drip.
pDark urine.
1.1. Analysis
1.1. Analysis
Comparison 1: Pyronaridine‐artesunate versus artemether‐lumefantrine, Outcome 1: Total failure: day 28 (PCR‐adjusted)
1.2. Analysis
1.2. Analysis
Comparison 1: Pyronaridine‐artesunate versus artemether‐lumefantrine, Outcome 2: Total failure: day 42 (PCR‐adjusted)
1.3. Analysis
1.3. Analysis
Comparison 1: Pyronaridine‐artesunate versus artemether‐lumefantrine, Outcome 3: Total failure: day 28 (unadjusted)
1.4. Analysis
1.4. Analysis
Comparison 1: Pyronaridine‐artesunate versus artemether‐lumefantrine, Outcome 4: Total failure: day 42 (unadjusted)
1.5. Analysis
1.5. Analysis
Comparison 1: Pyronaridine‐artesunate versus artemether‐lumefantrine, Outcome 5: Early treatment failure
1.6. Analysis
1.6. Analysis
Comparison 1: Pyronaridine‐artesunate versus artemether‐lumefantrine, Outcome 6: Serious adverse events
1.7. Analysis
1.7. Analysis
Comparison 1: Pyronaridine‐artesunate versus artemether‐lumefantrine, Outcome 7: Adverse events leading to withdrawal
1.8. Analysis
1.8. Analysis
Comparison 1: Pyronaridine‐artesunate versus artemether‐lumefantrine, Outcome 8: First treatment, ALT increase > 5 × ULN
1.9. Analysis
1.9. Analysis
Comparison 1: Pyronaridine‐artesunate versus artemether‐lumefantrine, Outcome 9: First treatment, AST increase > 5 × ULN
1.10. Analysis
1.10. Analysis
Comparison 1: Pyronaridine‐artesunate versus artemether‐lumefantrine, Outcome 10: First treatment, bilirubin increase > 2.5 × ULN
1.11. Analysis
1.11. Analysis
Comparison 1: Pyronaridine‐artesunate versus artemether‐lumefantrine, Outcome 11: Subsequent treatment(s), ALT increase > 5 × ULN
1.12. Analysis
1.12. Analysis
Comparison 1: Pyronaridine‐artesunate versus artemether‐lumefantrine, Outcome 12: Subsequent treatment(s), AST increase > 5 × ULN
1.13. Analysis
1.13. Analysis
Comparison 1: Pyronaridine‐artesunate versus artemether‐lumefantrine, Outcome 13: Subsequent treatment(s), bilirubin increase > 2.5 × ULN
1.14. Analysis
1.14. Analysis
Comparison 1: Pyronaridine‐artesunate versus artemether‐lumefantrine, Outcome 14: Paediatric trials ‐ total failure: day 28 (PCR‐adjusted)
1.15. Analysis
1.15. Analysis
Comparison 1: Pyronaridine‐artesunate versus artemether‐lumefantrine, Outcome 15: Paediatric trials ‐ total failure: day 42 (PCR‐adjusted)
1.16. Analysis
1.16. Analysis
Comparison 1: Pyronaridine‐artesunate versus artemether‐lumefantrine, Outcome 16: Paediatric trials ‐ total failure: day 28 (unadjusted)
1.17. Analysis
1.17. Analysis
Comparison 1: Pyronaridine‐artesunate versus artemether‐lumefantrine, Outcome 17: Paediatric trials ‐ total failure: day 42 (unadjusted)
1.18. Analysis
1.18. Analysis
Comparison 1: Pyronaridine‐artesunate versus artemether‐lumefantrine, Outcome 18: Paediatric trials ‐ first treatment, ALT increase > 5 × ULN
1.19. Analysis
1.19. Analysis
Comparison 1: Pyronaridine‐artesunate versus artemether‐lumefantrine, Outcome 19: Paediatric trials ‐ first treatment, AST increase > 5 × ULN
2.1. Analysis
2.1. Analysis
Comparison 2: Pyronaridine‐artesunate versus artesunate‐amodiaquine, Outcome 1: Total failure: day 28 (PCR‐adjusted)
2.2. Analysis
2.2. Analysis
Comparison 2: Pyronaridine‐artesunate versus artesunate‐amodiaquine, Outcome 2: Total failure: day 42 (PCR‐adjusted)
2.3. Analysis
2.3. Analysis
Comparison 2: Pyronaridine‐artesunate versus artesunate‐amodiaquine, Outcome 3: Total failure: day 28 (unadjusted)
2.4. Analysis
2.4. Analysis
Comparison 2: Pyronaridine‐artesunate versus artesunate‐amodiaquine, Outcome 4: Total failure: day 42 (unadjusted)
2.5. Analysis
2.5. Analysis
Comparison 2: Pyronaridine‐artesunate versus artesunate‐amodiaquine, Outcome 5: First treatment, ALT increase > 5 × ULN
2.6. Analysis
2.6. Analysis
Comparison 2: Pyronaridine‐artesunate versus artesunate‐amodiaquine, Outcome 6: First treatment, AST increase > 5 × ULN
2.7. Analysis
2.7. Analysis
Comparison 2: Pyronaridine‐artesunate versus artesunate‐amodiaquine, Outcome 7: First treatment, bilirubin increase > 2.5 × ULN
2.8. Analysis
2.8. Analysis
Comparison 2: Pyronaridine‐artesunate versus artesunate‐amodiaquine, Outcome 8: Subsequent treatment(s), ALT increase > 5 × ULN
2.9. Analysis
2.9. Analysis
Comparison 2: Pyronaridine‐artesunate versus artesunate‐amodiaquine, Outcome 9: Subsequent treatment(s), AST increase > 5 × ULN
2.10. Analysis
2.10. Analysis
Comparison 2: Pyronaridine‐artesunate versus artesunate‐amodiaquine, Outcome 10: Subsequent treatment(s), bilirubin increase > 2.5 × ULN
3.1. Analysis
3.1. Analysis
Comparison 3: Pyronaridine‐artesunate versus mefloquine plus artesunate, Outcome 1: Total failure: day 28 (PCR‐adjusted)
3.2. Analysis
3.2. Analysis
Comparison 3: Pyronaridine‐artesunate versus mefloquine plus artesunate, Outcome 2: Total failure: day 42 (PCR‐adjusted)
3.3. Analysis
3.3. Analysis
Comparison 3: Pyronaridine‐artesunate versus mefloquine plus artesunate, Outcome 3: Total failure: day 28 (unadjusted)
3.4. Analysis
3.4. Analysis
Comparison 3: Pyronaridine‐artesunate versus mefloquine plus artesunate, Outcome 4: Total failure: day 42 (unadjusted)
3.5. Analysis
3.5. Analysis
Comparison 3: Pyronaridine‐artesunate versus mefloquine plus artesunate, Outcome 5: Serious adverse events
3.6. Analysis
3.6. Analysis
Comparison 3: Pyronaridine‐artesunate versus mefloquine plus artesunate, Outcome 6: Adverse events leading to withdrawal
3.7. Analysis
3.7. Analysis
Comparison 3: Pyronaridine‐artesunate versus mefloquine plus artesunate, Outcome 7: First treatment, ALT increase > 5 × ULN
3.8. Analysis
3.8. Analysis
Comparison 3: Pyronaridine‐artesunate versus mefloquine plus artesunate, Outcome 8: First treatment, AST increase > 5 × ULN
3.9. Analysis
3.9. Analysis
Comparison 3: Pyronaridine‐artesunate versus mefloquine plus artesunate, Outcome 9: First treatment, bilirubin increase > 2.5 × ULN
4.1. Analysis
4.1. Analysis
Comparison 4: Pyronaridine‐artesunate versus other antimalarials for all malaria subtypes (safety outcomes only), Outcome 1: Serious adverse events
4.2. Analysis
4.2. Analysis
Comparison 4: Pyronaridine‐artesunate versus other antimalarials for all malaria subtypes (safety outcomes only), Outcome 2: Adverse events leading to withdrawal
4.3. Analysis
4.3. Analysis
Comparison 4: Pyronaridine‐artesunate versus other antimalarials for all malaria subtypes (safety outcomes only), Outcome 3: First treatment, ALT increase > 5 × ULN
4.4. Analysis
4.4. Analysis
Comparison 4: Pyronaridine‐artesunate versus other antimalarials for all malaria subtypes (safety outcomes only), Outcome 4: First treatment, AST increase > 5 × ULN
4.5. Analysis
4.5. Analysis
Comparison 4: Pyronaridine‐artesunate versus other antimalarials for all malaria subtypes (safety outcomes only), Outcome 5: First treatment, bilirubin increase > 2.5 × ULN
4.6. Analysis
4.6. Analysis
Comparison 4: Pyronaridine‐artesunate versus other antimalarials for all malaria subtypes (safety outcomes only), Outcome 6: Subsequent treatment(s), ALT increase > 5 × ULN
4.7. Analysis
4.7. Analysis
Comparison 4: Pyronaridine‐artesunate versus other antimalarials for all malaria subtypes (safety outcomes only), Outcome 7: Subsequent treatment(s), AST increase > 5 × ULN
4.8. Analysis
4.8. Analysis
Comparison 4: Pyronaridine‐artesunate versus other antimalarials for all malaria subtypes (safety outcomes only), Outcome 8: Subsequent treatment(s), bilirubin increase > 2.5 × ULN
4.9. Analysis
4.9. Analysis
Comparison 4: Pyronaridine‐artesunate versus other antimalarials for all malaria subtypes (safety outcomes only), Outcome 9: Sensitivity analysis: first treatment, ALT increase > 5 × ULN
4.10. Analysis
4.10. Analysis
Comparison 4: Pyronaridine‐artesunate versus other antimalarials for all malaria subtypes (safety outcomes only), Outcome 10: Other adverse events

References

References to studies included in this review Kayentao 2012 {published data only}

    1. Kayentao K, Doumbo OK, Pénali LK, Offianan AT, Bhatt KM, Kimani J, et al. Pyronaridine-artesunate granules versus artemether-lumefantrine crushed tablets in children with Plasmodium falciparum malaria: a randomized controlled trial. Malaria Journal 2012;11:364.
    1. Kayentao K. Pyronaridine-artesunate versus artemether/lumefantrine: efficacy in malaria patients with uncomplicated acute falciparum malaria: results of a pivotal Phase III trial. American Journal of Tropical Medicine and Hygiene 2008;79(Suppl 6):114.
    1. NCT00541385. Pyronaridine artesunate 3:1 granule formulation vs. Coartem© crushed tablets in P. falciparum malaria pediatric patients. (first received 10 October 2007).
Nelwan 2015 {published data only}
    1. Nelwan EJ, Ekawati LL, Tjahjono B, Setiabudy R, Sutanto I, Chand K, et al. Randomized trial of primaquine hypnozoitocidal efficacy when administered with artemisinin-combined blood schizontocides for radical cure of Plasmodium vivax in Indonesia. BMC Medicine 2015;13:294.
Poravuth 2011 {published data only}
    1. Duparc S, Borghini-Fuhrer I, Craft JC, Arbe-Barnes S, Miller RM, Shin CS, et al. Efficacy of pyronaridine/artesunate in clinical trials in patients with uncomplicated acute Plasmodium falciparum or Plasmodium vivax malaria: results of an integrated analysis. American Journal of Tropical Medicine and Hygiene 2009;81 Suppl:51-100.
    1. Duparc S, Borghini-Fuhrer I, Craft JC, Arbe-Barnes S, Miller RM, Shin CS, et al. Safety of pyronaridine/artesunate in clinical trials in patients with uncomplicated acute Plasmodium falciparum or Plasmodium vivax malaria: results of an integrated analysis. American Journal of Tropical Medicine and Hygiene 2009;81 Suppl:101-50.
    1. Poravuth Y, Socheat D, Rueangweerayut R, Uthaisin C, Pyae Phyo A, Valecha N, et al. Pyronaridine-artesunate versus chloroquine in patients with acute Plasmodium vivax malaria: a randomized, double-blind, non-inferiority trial. PLOS ONE 2011;6(1):e14501.
Ringwald 1996 {published data only}
    1. Ringwald P, Bickii J, Basco L. Randomised trial of pyronaridine versus chloroquine for acute uncomplicated falciparum malaria in Africa. Lancet 1996;347(8993):24-8.
    1. Ringwald P, Meche FS, Basco LK. Short report: effects of pyronaridine on gametocytes in patients with acute uncomplicated falciparum malaria. American Journal of Tropical Medicine and Hygiene 1999;61(3):446-8.
Ringwald 1998 {published data only}
    1. Ringwald P, Bickii J, Basco LK. Efficacy of oral pyronaridine for the treatment of acute uncomplicated falciparum malaria in African children. Clinical Infectious Diseases 1998;26(4):946-53.
Roth 2018a {published data only}
    1. Roth JM, Sawa P, Makio N, Omweri G, Osoti V, Okach S, et al. Pyronaridine–artesunate and artemether–lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Kenyan children: a randomized controlled non‑inferiority trial. Malaria Journal 2018;17(1):199.
Rueangweerayut 2012 {published data only}
    1. NCT00403260. Pyronaridine artesunate (3:1) versus mefloquine artesunate in P. falciparum malaria patients. (first received 21 November 2006).
    1. Rueangweerayut R, Phyo AP, Uchaisin C, Poravuth Y, Quang Binh T, Tinto H, et al. A randomized clinical trial comparing the efficacy and safety of fixed-dose pyronaridine-artesunate versus mefloquine plus artesunate in uncomplicated Plasmodium falciparum malaria. Submitted under review; personal communication by email from Isabelle Borghini Fuhrer, Medicines for Malaria Venture.
    1. Rueangweerayut R, Phyo AP, Uchaisin C, Socheat D, Quang Binh T, Tinto H, et al. Efficacy and safety of pyronaridine/artesunate fixed-dose combination compared with mefloquine plus artesunate in patients with acute uncomplicated Plasmodium falciparum malaria: results of a pivotal phase III trial. Tropical Medicine and International Health 2009;14 Suppl 2:30-97.
    1. Rueangweerayut R, Phyo AP, Uthaisin C, Poravuth Y, Binh TQ, Tinto H, et al. Pyronaridine-artesunate versus mefloquine plus artesunate for malaria. New England Journal of Medicine 2012;366(14):1298-309.
    1. Rueangweerayut R, Phyo AP, Uthaisin C, Poravuth Y, Binh TQ, Tinto H, et al. Supplement to: Pyronaridine–artesunate versus mefloquine plus artesunate for malaria. New England Journal of Medicine 2012;366(14):1298-309.
Sagara 2018 {published and unpublished data}
    1. Beshir KB, Diallo N, Fofana B, Traore A, Kodio A, Togo A, et al. Measuring the efficacy of four ACT regimens in Mali using qPCR-based estimates of Plasmodium falciparum clearance time. In: 63rd Annual Meeting of the American Society of Tropical Medicine and Hygiene; 2013 Nov 2-6; New Orleans. Arlington (VA): American Society of Tropical Medicine and Hygiene, 2014.
    1. Kabore TN, Barry N, Compaore YD, Nikiema F, Kabre Z, Fofana A. Randomized trial to assess the effect on qtc interval of repeated treatment of uncomplicated malaria with acts in Bobo-Dioulasso, Burkina Faso: relation between parasitemia and prolonged qtc. American Journal of Tropical Medicine and Hygiene 2017;97(5 Suppl 1):94.
    1. Sagara I, Beavogui AH, Zongo I, Soulama I, Borghini-Fuhrer I, Fofana B, et al. Pyronaridine-artesunate or dihydroartemisinin-piperaquine versus current first-line therapies for repeated treatment of uncomplicated malaria: a randomised, multicentre, open-label, longitudinal, controlled, phase 3b/4 trial. Lancet 2018;391(10128):1378-90. [DOI: 10.1016/S0140-6736(18)30291-5]
    1. Sagara I, Beavogui AH, Zongo I, Soulama I, Borghini-Fuhrer I, Fofana B, et al. Safety and efficacy of re-treatments with pyronaridine-artesunate in African patients with malaria: a substudy of the WANECAM randomised trial. Lancet Infectious Diseases 2016;16(2):189-98. [DOI: 10.1016/S1473-3099(15)00318-7]
    1. Soulama I, Coulibaly AS, Kabore JM, Ouattara MS, Bougouma EC, Sanon S. Assessment of the dynamics of Plasmodium falciparum parasitemia regarding three artemisinin combination regimens for acute uncomplicated malaria treatment, Banfora, Burkina Faso. American Journal of Tropical Medicine and Hygiene 2017;97(5 Suppl 1):317.
    1. Soulama I, Coulibaly AS, Kabore MJ, Ouattara M, Bougouma EC, Sanon S, et al. Safety and efficacy of repeated administration of pyronaridine-artesunate or dihydroartemisinin-piperaquine vs artesunate-amodiaquine in children and adult patients with acute uncomplicated Plasmodium sp malaria over of two years period at Banfora/Niangoloko site in Burkina Faso. American Journal of Tropical Medicine and Hygiene 2017;95(5 Suppl 1):479.
    1. Soulama I, Sirima SB. SBOC 8459 Assessment of parasite clearance after repeated treatment with artesunate amodiaquine, dihydroartemisinin-piperaquine, pyronaridine-artesunate in malaria patients in Burkina Faso. BMJ Global Health 2019;4:A7-8. [DOI: 10.1136/bmjgh-2019-EDC.17]
    1. Tekete M, Djimde A, Borrmann S. A phase IIIb/IV comparative, randomised, multi-centre, open label, parallel 3-arm clinical study to assess the safety and efficacy of repeated administration of four artemisinin-based combination therapy (ACT) over a two-year period in children and adult patients with acute uncomplicated Plasmodium sp. malaria. Jahrestreffen der AG Malaria der Sektion Antiparasitare Chemotherapie der Paul-Ehrlich-Gesellschaft fur Chemotherapie 2012;9.
Sagara 2018 (Bobo‐Doiulasso, Burkina Faso) {published and unpublished data}
    1. Compaoré YD, Zongo I, Somé AF, Barry N, Nikiema F, Kabore TN, et al. Hepatic safety of repeated treatment with pyronaridine‐artesunate versus artemether–lumefantrine in patients with uncomplicated malaria: a secondary analysis of the WANECAM 1 data from Bobo-Dioulasso, Burkina Faso. Malaria Journal 2021;20:64. [DOI: 10.1186/s12936-021-03593-6]
    1. WANECAM trial authors. Site data: Bobo, Burkina Faso (as supplied 6 July 2017). Data on file.
Sagara 2018 (Bougoula, Mali) {published and unpublished data}
    1. WANECAM trial authors. Site data: Bougala, Mali (as supplied 6 July 2017). Data on file.
Sagara 2018 (Djoliba, Mali) {published and unpublished data}
    1. WANECAM trial authors. Site data: Djoliba, Mali (as supplied 6 July 2017). Data on file.
Sagara 2018 (Kolle, Mali) {published and unpublished data}
    1. WANECAM trial authors. Site data: Kolle, Mali (as supplied 6 July 2017). Data on file.
Sagara 2018 (Mafrinyah, Guinea) {published and unpublished data}
    1. WANECAM trial authors. Site data: Mafrinyah, Guinea (as supplied 6 July 2017). Data on file.
Sagara 2018 (Ouagadougou, Burkina Faso) {published and unpublished data}
    1. WANECAM trial authors. Site data: Ouaga, Burkina Faso (as supplied 6 July 2017). Data on file.
Sagara 2018 (Sotuba, Mali) {published and unpublished data}
    1. WANECAM trial authors. Site data: Sotuba, Mali (as supplied 6 July 2017). Data on file.
Shin 2011 {published and unpublished data}
    1. Shin CS, Kwak YG, Lee KD, Borghini Fuhrer I, Miller RM, Duparc S. Treatment of Korean vivax malaria patients with the fixed-dose combination of pyronaridine:artesunate. Tropical Medicine and International Health 2011;16 Suppl 1:97-384. [ABSTRACT NO.: 1.1-169]
Tshefu 2010 {published data only}
    1. Duparc S, Borghini-Fuhrer I, Craft JC, Arbe-Barnes S, Miller RM, Shin CS, et al. Efficacy of pyronaridine/artesunate in clinical trials in patients with uncomplicated acute Plasmodium falciparum or Plasmodium vivax malaria: results of an integrated analysis. American Journal of Tropical Medicine and Hygiene 2009;81 Suppl:51-100.
    1. Duparc S, Borghini-Fuhrer I, Craft JC, Arbe-Barnes S, Miller RM, Shin CS, et al. Safety of pyronaridine/artesunate in clinical trials in patients with uncomplicated acute Plasmodium falciparum or Plasmodium vivax malaria: results of an integrated analysis. American Journal of Tropical Medicine and Hygiene 2009;81 Suppl:101-50.
    1. Tshefu AK, Gaye O, Kayentao K, Thompson R, Bhatt KM, Sesay SS, et al. 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(9724):1457-67.
References to studies excluded from this review Bui 2020 {published data only}
    1. Bui PQ, Huynh QH, Tran DT, Le DT, Nguyen TQ, Truong HV, et al. Pyronaridine-artesunate efficacy and safety in uncomplicated Plasmodium falciparum malaria in areas of Artemisin-resistant falciparum in Viet Nam (2017-2018). Clinical Infectious Diseases 2020;70(10):2187.
Han 2020 {published data only}
    1. Han KT, Lin K, Han ZY, Myint MK, Aye KH, Thi A, et al. Efficacy and safety of Pyronaridine-artesunate for the treatment of uncomplicated Plasmodium falciparum and Plasmodium vivax malaria in Myanmar. American Journal of Tropical Medicine and Hygiene 2020;103(3):1088.
Huang 1988   {published data only}
    1. Huang ZS, Shao BR, Meng F, Zeng LH, Ye XY, Huang J, et al. Effects of combined dose of pyronaridine/sulfadoxine/pyrimethamine on falciparum malaria. Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi [Chinese Journal of Parasitology and Parasitic Diseases] 1988;6(4):285-8.
Huang 1989 {published data only}
    1. Huang ZS, Feng Z, Meng F, Zeng LH, Lin X, Zhen Y, et al. Therapeutic effect of pyronaridine in plain tablets and enteric coated tablets in falciparum malaria patients. Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi [Chinese Journal of Parasitology and Parasitic Diseases] 1989;7(1):19-21.
Huang 1993 {published data only}
    1. Huang Z, Shao B, Meng F, Shi X. Comparison of different regimen of pyronaridine and sulfadoxine combined with pyrimethamine in the treatment of malignant malaria. Chinese Journal of Infectious Diseases 1993;11(Suppl 3):175-7. [ISSN: CN-00256187]
Laman 2014 {published data only}
    1. Laman M, Moore BR, Benjamin JM, Yadi G, Bona C, Warrel J. Artemisinin-naphthoquine versus artemether-lumefantrine for uncomplicated malaria in Papua New Guinean children: an open-label randomized trial. PLOS Medicine 2014;11(12):e1001773.
Leang 2016 {published data only}
    1. Leang R, Canavati SE, Khim N, Vestergaard LS, Borghini Fuhrer I, Kim S, et al. Efficacy and safety of pyronaridine-artesunate for the treatment of uncomplicated Plasmodium falciparum malaria in western Cambodia. Antimicrobial Agents and Chemotherapy 2016;60(7):3884-90.
Leang 2019a {published data only}
    1. Leang R, Khim N, Chea H, Huy R, Mairet-Khedim M, Bouth DM, et al. Efficacy and safety of Pyronaridine-artesunate plus single-dose Primaquine for the treatment of malaria in Western Cambodia. Antimicrobial Agents and Chemotherapy 2019;63:1273.
Leang 2019b {published data only}
    1. Leang R, Mairet-Khedim M, Chea H, Huy R, Khim N, Bouth DM, et al. Efficacy and safety of Pyronaridine-artesunate plus single-dose Primaquine for treatment of uncomplicated Plasmodium falciparum malaria in Eastern Cambodia. Antimicrobial Agents and Chemotherapy 2019;63:2242.
Looareesuwan 1996   {published data only}
    1. Looareesuwan S, Kyle DE, Viravan C, Vanijanonta S, Wilairatana P, Wernsdorfer WH. Clinical study of pyronaridine for the treatment of acute uncomplicated falciparum malaria in Thailand. American Journal of Tropical Medicine and Hygiene 1996;54(2):205-9.
Looareesuwan 2007 {published data only}
    1. Looareesuwan S, Gaye O, Tjitra E, Bojang K, Socheat D, Piola P. Results of a randomized, multicentre, phase II, dose-ranging, clinical study to assess the safety and efficacy of fixed dose, orally administered pyronaridine and artesunate in adult patients with acute uncomplicated Plasmodium falciparum malaria. American Journal of Tropical Medicine and Hygiene 2007;77(5):1004.
Lutete 2021a {published data only}
    1. Lutete GT, Mombo-Ngoma G, Assi SB, Bigoga JD, Koukouikila-Koussounda F, Ntamabyaliro NY, et al. Pyronaridine-artesunate real-world safety, tolerability, and effectiveness in malaria patients in 5 African countries: a single-arm, open-label, cohort event monitoring study. PLOS Medicine 2021;16(6):e1003669.
Piola 2008 {published data only}
    1. Piola P, Fleckenstein L. Pharmacokinetics, clinical and safety outcomes of pyronaridine/artesunate treatment of acute Plasmodium falciparum malaria in Uganda. American Journal of Tropical Medicine and Hygiene 2008;79(6):855.
Ramharter 2008 {published data only}
    1. Ramharter M, Kurth F, Schreier AC, Nemeth J, Glasenapp Iv, Bélard S, et al. Fixed-dose pyronaridine-artesunate combination for treatment of uncomplicated falciparum malaria in pediatric patients in Gabon. Journal of Infectious Diseases 2008;198(6):911-9.
Roth 2018b {published data only}
    1. Roth JA, Sawa P, Omweri J, Makio N, Osoti V, Jong MD, et al. Molecular detection of residual parasitemia after pyronaridine–artesunate or artemether–lumefantrine treatment of uncomplicated Plasmodium falciparum malaria in Kenyan children. American Journal of Tropical Medicine and Hygiene 2018;99(4):970-7.
Sagara 2014 {published data only}
    1. Sagara I, Piarroux R, Djimde A, Giorgi R, Kayentao K, Doumbo OK, et al. Delayed anemia assessment in patients treated with oral artemisinin derivatives for uncomplicated malaria: a pooled analysis of clinical trials data from Mali. Malaria Journal 2014;13(1):358.
References to ongoing studies NCT03726593 {unpublished data only}
    1. NCT03726593. Drug combinations of Atovaquone-Proguanil (AP) with ACT (APACT). (first received 31 October 2018).
NCT03814616 {unpublished data only}
    1. NCT03814616. Pyramax in asymptomatic carriers of P. falciparum monoinfections. (first received 24 January 2019).
Additional references Aithal 2011
    1. Aithal GP, Watkins PB, Andrade RJ, Larrey D, Molokhia M, Takikawa H, et al. Case definition and phenotype standardization in drug-induced liver injury. Clinical Pharmacology & Therapeutics 2011;89(6):806-15.
Basco 1992
    1. Basco LK, Le Bras J. In vitro activity of pyronaridine against African strains of Plasmodium falciparum. Annals of Tropical Medicine and Parasitology 1992;86(5):447-54.
Chang 1992
    1. Chang C, Lin-Hua T, Jantanavivat C. Studies on a new antimalarial compound: pyronaridine. Transactions of the Royal Society of Tropical Medicine and Hygiene 1992;86(1):7-10.
Chavalitshewinkoon‐Petmitr 2000
    1. Chavalitshewinkoon-Petmitr P, Pongvilairat G, Auparakkitanon S, Wilairat P. Gametocytocidal activity of pyronaridine and DNA topoisomerase II inhibitors against multidrug-resistant Plasmodium falciparum in vitro. Parasitology International 2000;48(4):275-80.
Childs 1988
    1. Childs GE, Häusler B, Milhous W, Chen C, Wimonwattrawatee T, Pooyindee N, et al. In vitro activity of pyronaridine against field isolates and reference clones of Plasmodium falciparum. American Journal of Tropical Medicine and Hygiene 1988;38(1):24-9.
Croft 2012
    1. Croft SL, Duparc S, Arbe-Barnes SJ, Craft JC, Shin CS, Fleckenstein L, et al. Review of pyronaridine anti-malarial properties and product characteristics. Malaria Journal 2012;11:270.
Dondorp 2009
    1. Dondorp AM, Nosten F, Yi P, Das D, Phyo AP, Tarning J, et al. Artemisinin resistance in Plasmodium falciparum malaria. New England Journal of Medicine 2009;351(5):455-67.
Duparc 2013
    1. Duparc S, Borghini-Fuhrer I, Craft CJ, Arbe-Barnes S, Miller RM, Shin CS, et al. Safety and efficacy of pyronaridine-artesunate in uncomplicated acute malaria: an integrated analysis of individual patient data from six randomized clinical trials. Malaria Journal 2013;12:70. [DOI: 10.1186/1475-2875-12-70]
Fu 1991
    1. Fu S, Xiao SH. Pyronaridine: a new antimalarial drug. Parasitology Today 1991;7(11):310-3.
GRADEpro GDT [Computer program]
    1. McMaster University (developed by Evidence Prime) GRADEpro GDT. Version accessed 11 November 2021. Hamilton (ON): McMaster University (developed by Evidence Prime). Available at .
Higgins 2011
    1. Higgins JP, Altman DG, Sterne JA, editor(s). Chapter 8: Assessing risk of bias in included studies. In: Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from .
Juni 2001
    1. Jüni P, Altman DG, Egger M. Assessing the quality of controlled clinical trials. BMJ 2001;323:42.
Kurth 2009
    1. Kurth F, Pongratz P, Bélard S, Mordmüller B, Kremsner PG, Ramharter M. In vitro activity of pyronaridine against Plasmodium falciparum and comparative evaluation of anti-malarial drug susceptibility assays. Malaria Journal 2009;8:79.
Lefebvre 2011
    1. Lefebvre C, Manheimer E, Glanville J. Chapter 6: Searching for studies. In: Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from .
Loke 2007
    1. Loke YK, Price D, Herxheimer A, Cochrane Adverse Effects Methods Group. Systematic reviews of adverse effects: framework for a structured approach. BMC Medical Research Methodology 2007;7(32):1-9.
Lubell 2014
    1. Lubell Y, Dondorp A, Guerin PJ, Drake T, Meek S, Ashley E, et al. Artemisinin resistance - modelling the potential human and economic costs. Malaria Journal 2014;13(452):1-9.
Lutete 2021b
    1. Lutete TG, Mombo-Ngoma G, Assi SB, Bigoga JD, Koukouikila-Koussounda F, Ntamabyaliro NY, et al. Pyronaridine–artesunate real-world safety, tolerability, and effectiveness in malaria patients in 5 African countries: a single-arm, open-label, cohort event monitoring study. PLOS Medicine 2021;18(6):e1003669.
MedDRA 2016 [Computer program]
    1. International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Medical Dictionary for Regulatory Activities. Version accessed 19 October 2018. International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, 2016. Available at .
MMV 2002
    1. TDR/Medicines for Malaria Venture/Shin Poong Pharmaceuticals Inc. WHO TDR/Medicines for Malaria Venture/Shin Poong Pharmaceuticals Inc. sign agreement for development of pyronaridine-artesunate for treatment of malaria. (accessed 17 April 2018).
Moher 2009
    1. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLOS Medicine 2009;6(7):e1000097.
Noedl 2008
    1. Noedl H, Se Y, Schaecher K, Smith BL, Socheat D, Fukuda MM. Evidence of artemisinin-resistant malaria in western Cambodia. New England Journal of Medicine 2008;359(24):2619-20.
Peters 1997
    1. Peters W, Robinson BL. The chemotherapy of rodent malaria. LV. Interactions between pyronaridine and artemisinin. Annals of Tropical Medicine and Parasitology 1997;91(2):141-5.
Pradines 1998
    1. Pradines B, Tall A, Parzy D, Spiegel A, Fusai T, Hienne R, et al. In-vitro activity of pyronaridine and amodiaquine against African isolates (Senegal) of Plasmodium falciparum in comparison with standard antimalarial agents. Journal of Antimicrobial Chemotherapy 1998;42(3):333-9.
Price 2010
    1. Price RN, Marfurt J, Chalfein F, Kenangalem E, Piera KA, Tjitra E, et al. In vitro activity of pyronaridine against multidrug-resistant Plasmodium falciparum and Plasmodium vivax. Antimicrobial Agents and Chemotherapy 2010;54(12):5146-50.
Review Manager 2020 [Computer program]
    1. Nordic Cochrane Centre, The Cochrane Collaboration Review Manager 5 (RevMan 5). Version 5.4. Copenhagen: Nordic Cochrane Centre, The Cochrane Collaboration, 2020.
Ringwald 1999
    1. Ringwald P, Eboumbou EC, Bickii J, Basco LK. In vitro activities of pyronaridine, alone and in combination with other antimalarial drugs, against Plasmodium falciparum. Antimicrobial Agents and Chemotherapy 1999;43(6):1525-7.
Schünemann 2013
    1. Schünemann H, Brożek J, Guyatt G, Oxman A, editor(s). Handbook for grading the quality of evidence and the strength of recommendations using the GRADE approach (updated October 2013). GRADE Working Group, 2013. Available from .
Schünemann 2019
    1. Schünemann HJ, Vist GE, Higgins JP, Santesso N, Deeks JJ, Glasziou P, et al. Chapter 15: Interpreting results and drawing conclusions. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editors(s). Cochrane Handbook for Systematic Reviews of Interventions. 2nd edition. Chichester (UK): John Wiley & Sons, 2019 :403-31.
Sinclair 2009
    1. Sinclair D, Zani B, Donegan S, Olliaro P, Garner P. Artemisinin-based combination therapy for treating uncomplicated malaria. Cochrane Database of Systematic Reviews 2009, Issue 3. Art. No: CD007483. [DOI: 10.1002/14651858.CD007483.pub2]
Tickell‐Painter 2017
    1. Tickell‐Painter M, Maayan N, Saunders R, Pace C, Sinclair D. Mefloquine for preventing malaria during travel to endemic areas. Cochrane Database of Systematic Reviews 2017, Issue 10. Art. No: CD006491. [DOI: 10.1002/14651858.CD006491.pub4]
Vivas 2008
    1. Vivas L, Rattray L, Stewart L, Bongard E, Robinson BL, Peters W, et al. Anti-malarial efficacy of pyronaridine and artesunate in combination in vitro and in vivo. Acta Tropica 2008;105(3):222-8.
WHO 2003
    1. World Health Organization. Assessment and monitoring of antimalarial drug efficacy for the treatment of uncomplicated falciparum malaria. December 2003. (accessed 1 September 2017).
WHO 2006
    1. World Health Organization. WHO guidelines for the treatment of malaria. 2006. .
WHO 2009
    1. World Health Organization. Methods for surveillance of antimalarial drug efficacy. November 2009. (accessed 1 September 2017).
WHO 2011
    1. World Health Organization. Global plan for artemisinin resistance containment (GPARC). (accessed 4 February 2011).
WHO 2015
    1. World Health Organization. Guidelines for the treatment of malaria - 3rd edition. April 2015. (accessed 1 September 2017).
WHO 2017
    1. World Health Organization. World Malaria Report 2017. .
WHO 2019
    1. World Health Organization. ACSOMP recommendations 2019. (accessed 4 November 2021).
WHO 2020
    1. World Health Organization. World Malaria Report 2020. (accessed 4 November 2021).
WHO 2022
    1. World Health Organization. WHO guidelines for malaria. Geneva: World Health Organization; 31 March 2022. WHO/UCN/GMP/ 2022.01 Rev.1.
Zorzela 2016
    1. Zorzela L, Loke YK, Ioannidis JP, Golder S, Santaguida P, Altman DG, et al, PRISMA Harms Group. PRISMA harms checklist: improving harms reporting in systematic reviews. BMJ 2016;352(157):1-17.
References to other published versions of this review Bukirwa 2014
    1. Bukirwa H, Unnikrishnan B, Kramer CV, Sinclair D, Nair S, Tharyan P. Artesunate plus pyronaridine for treating uncomplicated Plasmodium falciparum malaria. Cochrane Database of Systematic Reviews 2014, Issue 3. Art. No: CD006404. [DOI: 10.1002/14651858.CD006404.pub2]
Pryce 2019
    1. Pryce J, Hine P. Pyronaridine‐artesunate for treating uncomplicated Plasmodium falciparum malaria. Cochrane Database of Systematic Reviews 2019, Issue 1. Art. No: CD006404. [DOI: 10.1002/14651858.CD006404.pub3]
Unnikrishnan 2007
    1. Unnikrishnan B, Nair S, Aravindakshan R. Pyronaridine for treating uncomplicated malaria. Cochrane Database of Systematic Reviews 2007, Issue 1. Art. No: CD006404. [DOI: 10.1002/14651858.CD006404]

Source: PubMed

Спонсоры и соавторы

Заболевания

Медикаментозные вмешательства

Подписаться