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Title: Acetaminophen as a renoprotective adjunctive treatment in patients with severe and moderately severe falciparum malaria : a randomized, controlled, open-label trial
Authors: Charunwatthana, Prakaykaew
Silamut, Kamolrat
Yeo, Tsin Wen
Lee, Sue J.
Mukaka, Mavuto
Maude, Richard J.
Plewes, Katherine
Md. Mahtab Uddin Hassan
Selim Md. Jahangir
Anstey, Nicholas M.
Md. Abul Faiz
Tarning, Joel
Oates, John A.
Kingston, Hugh W. F.
Ghose, Aniruddha
Wattanakul, Thanaporn
Md. Shafiul Haider
Dutta, Prodip K.
Md. Akhterul Islam
Shamsul Alam
Zahed, A. S. M.
Md. Abdus Sattar
Chowdhury, M. A. Hassan
Herdman, M. Trent
Leopold, Haruhiko
Piera, Kim A
White, Nicholas J.
Md. Amir Hossain
Roberts II, L. Jackson
Dondorp, Arjen M.
Turner, Gareth D. H.
Day, Nicholas P. J.
Keywords: Science::Medicine
Falciparum Malaria
Acute Kidney Injury
Issue Date: 2018
Source: Plewes, K., Kingston, H. W. F., Ghose, A., Wattanakul, T., Hassan, M. M. U., Haider, M. S., . . . Dondorp, A. M. (2018). Acetaminophen as a renoprotective adjunctive treatment in patients with severe and moderately severe falciparum malaria : a randomized, controlled, open-label trial. Clinical Infectious Diseases, 67(7), 991-999. doi:10.1093/cid/ciy213
Series/Report no.: Clinical Infectious Diseases
Abstract: 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.
ISSN: 1058-4838
DOI: 10.1093/cid/ciy213
Rights: © 2018 The Author(s). Published by Oxford University Press for the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Fulltext Permission: open
Fulltext Availability: With Fulltext
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