Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/86022
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dc.contributor.authorCooper, Daniel J.en
dc.contributor.authorPlewes, Katherineen
dc.contributor.authorGrigg, Matthew J.en
dc.contributor.authorRajahram, Giri S.en
dc.contributor.authorPiera, Kim A.en
dc.contributor.authorWilliam, Timothyen
dc.contributor.authorChatfield, Mark D.en
dc.contributor.authorYeo, Tsin Wenen
dc.contributor.authorDondorp, Arjen M.en
dc.contributor.authorAnstey, Nicholas M.en
dc.contributor.authorBarber, Bridget E.en
dc.date.accessioned2018-07-26T08:36:43Zen
dc.date.accessioned2019-12-06T16:14:32Z-
dc.date.available2018-07-26T08:36:43Zen
dc.date.available2019-12-06T16:14:32Z-
dc.date.issued2018en
dc.identifier.citationCooper, D. J., Plewes, K., Grigg, M. J., Rajahram, G. S., Piera, K. A., William, T., et al. (2018). The effect of regularly dosed paracetamol versus no paracetamol on renal function in Plasmodium knowlesi malaria (PACKNOW) : study protocol for a randomised controlled trial. Trials, 19, 250-.en
dc.identifier.urihttps://hdl.handle.net/10356/86022-
dc.description.abstractBackground: Plasmodium knowlesi is the most common cause of human malaria in Malaysia. Acute kidney injury (AKI) is a frequent complication. AKI of any cause can have long-term consequences, including increased risk of chronic kidney disease, adverse cardiovascular events and increased mortality. Additional management strategies are therefore needed to reduce the frequency and severity of AKI in malaria. In falciparum malaria, cell-free haemoglobin (CFHb)-mediated oxidative damage contributes to AKI. The inexpensive and widely available drug paracetamol inhibits CFHb-induced lipid peroxidation via reduction of ferryl haem to the less toxic Fe3+ state, and has been shown to reduce oxidative damage and improve renal function in patients with sepsis complicated by haemolysis as well as in falciparum malaria. This study aims to assess the ability of regularly dosed paracetamol to reduce the incidence and severity of AKI in knowlesi malaria by attenuating haemolysis-induced oxidative damage. Methods: PACKNOW is a two-arm, open-label randomised controlled trial of adjunctive paracetamol versus no paracetamol in patients aged ≥ 5 years with knowlesi malaria, conducted over a 2-year period at four hospital sites in Sabah, Malaysia. The primary endpoint of change in creatinine from enrolment to 72 h will be evaluated by analysis of covariance (ANCOVA) using enrolment creatinine as a covariate. Secondary endpoints include longitudinal changes in markers of oxidative stress (plasma F2-isoprostanes and isofurans) and markers of endothelial activation/Weibel–Palade body release (angiopoietin-2, von Willebrand Factor, P-selectin, osteoprotegerin) over 72 h, as well as blood and urine biomarkers of AKI. This study will be powered to detect a difference between the two treatment arms in a clinically relevant population including adults and children with knowlesi malaria of any severity. Discussion: Paracetamol is widely available and has an excellent safety profile; if a renoprotective effect is demonstrated, this trial will support the administration of regularly dosed paracetamol to all patients with knowlesi malaria. The secondary outcomes in this study will provide further insights into the pathophysiology of haemolysis-induced oxidative damage and acute kidney injury in knowlesi malaria and other haemolytic diseases.en
dc.format.extent11 p.en
dc.language.isoenen
dc.relation.ispartofseriesTrialsen
dc.rights© 2018 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.en
dc.subjectMalariaen
dc.subjectPlasmodium Knowlesien
dc.titleThe effect of regularly dosed paracetamol versus no paracetamol on renal function in Plasmodium knowlesi malaria (PACKNOW) : study protocol for a randomised controlled trialen
dc.typeJournal Articleen
dc.contributor.schoolLee Kong Chian School of Medicine (LKCMedicine)en
dc.identifier.doi10.1186/s13063-018-2600-0en
dc.description.versionPublished versionen
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item.grantfulltextopen-
Appears in Collections:LKCMedicine Journal Articles

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