Journal article
The effect of regularly dosed acetaminophen vs no acetaminophen on renal function in plasmodium knowlesi malaria (PACKNOW): a randomized, controlled trial
- Abstract:
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Background
Acetaminophen inhibits cell-free hemoglobin-induced lipid peroxidation and improves renal function in severe falciparum malaria but has not been evaluated in other infections with prominent hemolysis, including Plasmodium knowlesi malaria.
Methods
PACKNOW was an open-label, randomized, controlled trial of acetaminophen (500 mg or 1000 mg every 6 hours for 72 hours) vs no acetaminophen in Malaysian patients aged ≥5 years with knowlesi malaria of any severity. The primary end point was change in creatinine at 72 hours. Secondary end points included longitudinal changes in creatinine in patients with severe malaria or acute kidney injury (AKI), stratified by hemolysis.
Results
During 2016–2018, 396 patients (aged 12–96 years) were randomized to acetaminophen (n = 199) or no acetaminophen (n = 197). Overall, creatinine fell by a mean (standard deviation) 14.9% (18.1) in the acetaminophen arm vs 14.6% (16.0) in the control arm (P = .81). In severe disease, creatinine fell by 31.0% (26.5) in the acetaminophen arm vs 20.4% (21.5) in the control arm (P = .12), and in those with hemolysis by 35.8% (26.7) and 19% (16.6), respectively (P = .07). No difference was seen overall in patients with AKI; however, in those with AKI and hemolysis, creatinine fell by 34.5% (20.7) in the acetaminophen arm vs 25.9% (15.8) in the control arm (P = .041). Mixed-effects modeling demonstrated a benefit of acetaminophen at 72 hours (P = .041) and 1 week (P = .002) in patients with severe malaria and with AKI and hemolysis (P = .027 and P = .002, respectively).
Conclusions
Acetaminophen did not improve creatinine among the entire cohort but may improve renal function in patients with severe knowlesi malaria and in those with AKI and hemolysis.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 1.4MB, Terms of use)
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- Publisher copy:
- 10.1093/cid/ciac152
Authors
- Publisher:
- Oxford University Press
- Journal:
- Clinical Infectious Diseases More from this journal
- Volume:
- 75
- Issue:
- 8
- Pages:
- 1379-1388
- Publication date:
- 2022-02-18
- Acceptance date:
- 2022-02-13
- DOI:
- EISSN:
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1537-6591
- ISSN:
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1058-4838
- Pmid:
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35180298
- Language:
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English
- Keywords:
- Pubs id:
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1241386
- Local pid:
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pubs:1241386
- Deposit date:
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2023-01-09
Terms of use
- Copyright holder:
- Cooper et al.
- Copyright date:
- 2022
- Rights statement:
- © The Author(s) 2022. 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-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/ by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited.
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