Publication:
Acetaminophen as a Renoprotective Adjunctive Treatment in Patients with Severe and Moderately Severe Falciparum Malaria: A Randomized, Controlled, Open-Label Trial

Issued Date

2018-09-14

Resource Type

Article

ISSN

15376591
10584838

DOI

10.1093/cid/ciy213

Other identifier(s)

2-s2.0-85045900185

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

Clinical Infectious Diseases. Vol.67, No.7 (2018), 991-999

Suggested Citation

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 Acetaminophen as a Renoprotective Adjunctive Treatment in Patients with Severe and Moderately Severe Falciparum Malaria: A Randomized, Controlled, Open-Label Trial. Clinical Infectious Diseases. Vol.67, No.7 (2018), 991-999. doi:10.1093/cid/ciy213 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/46325

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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

Author(s)

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

Other Contributor(s)

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

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.

Keyword(s)

Medicine

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URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/46325

Collections

Scopus 2018