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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/46747
Title: The effect of regularly dosed paracetamol versus no paracetamol on renal function in Plasmodium knowlesi malaria (PACKNOW): Study protocol for a randomised controlled trial
Authors: Daniel J. Cooper
Katherine Plewes
Matthew J. Grigg
Giri S. Rajahram
Kim A. Piera
Timothy William
Mark D. Chatfield
Tsin Wen Yeo
Arjen M. Dondorp
Nicholas M. Anstey
Bridget E. Barber
Menzies School of Health Research
QIMR Berghofer Medical Research Institute
Mahidol University
The University of British Columbia
Nuffield Department of Clinical Medicine
Nanyang Technological University
Queen Elizabeth Hospital
Jesselton Medical Centre
Infectious Diseases Society Sabah-Menzies School of Health Research Clinical Research Unit
Sabah Department of Health
Keywords: Medicine
Issue Date: 24-Apr-2018
Citation: Trials. Vol.19, No.1 (2018)
Abstract: © 2018 The Author(s). Background: 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 Fe 3+ 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 F 2 -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.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85045884944&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/46747
ISSN: 17456215
Appears in Collections:Scopus 2018

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