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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/46325
Title: Acetaminophen as a Renoprotective Adjunctive Treatment in Patients with Severe and Moderately Severe Falciparum Malaria: A Randomized, Controlled, Open-Label Trial
Authors: Katherine Plewes
Hugh W.F. Kingston
Aniruddha Ghose
Thanaporn Wattanakul
Md Mahtab Uddin Hassan
Md Shafiul Haider
Prodip K. Dutta
Md Akhterul Islam
Shamsul Alam
Selim Md Jahangir
A. S.M. Zahed
Md Abdus Sattar
M. A.Hassan Chowdhury
M. Trent Herdman
Stije J. Leopold
Haruhiko Ishioka
Kim A. Piera
Prakaykaew Charunwatthana
Kamolrat Silamut
Tsin W. Yeo
Sue J. Lee
Mavuto Mukaka
Richard J. Maude
Gareth D.H. Turner
Md Abul Faiz
Joel Tarning
John A. Oates
Nicholas M. Anstey
Nicholas J. White
Nicholas P.J. Day
Md Amir Hossain
L. Jackson Roberts
Arjen M. Dondorp
Harvard School of Public Health
Menzies School of Health Research
Mahidol University
Chittagong Medical College Hospital
The University of British Columbia
Nuffield Department of Clinical Medicine
Vanderbilt University School of Medicine
Nanyang Technological University
Ramu Upazilla Health Complex
Dev Care Foundation
Keywords: Medicine
Issue Date: 14-Sep-2018
Citation: Clinical Infectious Diseases. Vol.67, No.7 (2018), 991-999
Abstract: © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. Background Acute kidney injury independently predicts mortality in falciparum malaria. It is unknown whether acetaminophen's capacity to inhibit plasma hemoglobin-mediated oxidation is renoprotective in severe malaria. Methods This phase 2, open-label, randomized controlled trial conducted at two hospitals in Bangladesh assessed effects on renal function, safety, pharmacokinetic (PK) properties and pharmacodynamic (PD) effects of acetaminophen. Febrile patients (>12 years) with severe falciparum malaria were randomly assigned to receive acetaminophen (1 g 6-hourly for 72 hours) or no acetaminophen, in addition to intravenous artesunate. Primary outcome was the proportional change in creatinine after 72 hours stratified by median plasma hemoglobin. Results Between 2012 and 2014, 62 patients were randomly assigned to receive acetaminophen (n = 31) or no acetaminophen (n = 31). Median (interquartile range) reduction in creatinine after 72 hours was 23% (37% to 18%) in patients assigned to acetaminophen, versus 14% (29% to 0%) in patients assigned to no acetaminophen (P =.043). This difference in reduction was 37% (48% to 22%) versus 14% (30% to -71%) in patients with hemoglobin ≥45000 ng/mL (P =.010). The proportion with progressing kidney injury was higher among controls (subdistribution hazard ratio, 3.0; 95% confidence interval, 1.1 to 8.5; P =.034). PK-PD analyses showed that higher exposure to acetaminophen increased the probability of creatinine improvement. No patient fulfilled Hy's law for hepatotoxicity. Conclusions In this proof-of-principle study, acetaminophen showed renoprotection without evidence of safety concerns in patients with severe falciparum malaria, particularly in those with prominent intravascular hemolysis. Clinical Trials Registration NCT01641289.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85045900185&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/46325
ISSN: 15376591
10584838
Appears in Collections:Scopus 2018

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