Evidence mapPaperPMID 29538635Full record

Trial reportClinical infectious diseases : an official publication of the Infectious Diseases Society of America2018

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

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 and 23 more

2 registry-linked trialsOpen access · hybridAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
6.4field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01641289 nacompletednot on this map

Paracetamol Effect on Oxidative Stress and Renal Function in Severe Falciparum Malaria With Intravascular Haemolysis: A Randomised Controlled Clinical Trial

TypeinterventionalSponsorUniversity of OxfordRan2012 to 2014Enrolled62ConditionsMalariaArmsParacetamol, No Paracetamol
NCT05746819 completednot on this mapstarted 2021, after this paper: background citation

An MRI Ancillary Study of a Malaria Fever Randomized Controlled Trial (RCT)

TypeobservationalSponsorUniversity of RochesterRan2021 to 2024Enrolled181ConditionsBrain Injuries, Malaria, MRI Imaging, Neurocognitive DeficitsArmsAggressive antipyretics therapy of fever vs usual care in the Malaria RCT study
3 · Its place in the literature

Who cites it

42 citing papers in PubMed, 64 citations in OpenAlex.

  1. Trial
  2. Trial
  3. The Effect of Regularly Dosed Acetaminophen vs No Acetaminophen on Renal Function in Plasmodium knowlesi Malaria (PACKNOW): A Randomized, Controlled Trial.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022
    Trial
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Malaria.The New England journal of medicine · 2025
    Review
  10. Article
  11. CD8Frontiers in cellular and infection microbiology · 2025
    Article
  12. ISCCM Position Statement on the Management of Severe Malaria in Intensive Care Unit.Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine · 2024
    Article
  13. Review
  14. Review
  15. Article
  16. Article
  17. Review
  18. Acetaminophen as Renoprotective Treatment in a Patient With Severe Malaria.Federal practitioner : for the health care professionals of the VA, DoD, and PHS · 2023
    Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

33 authors at 8 institutions in 7 countries.

Katherine PlewesMahidol Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand.
Hugh W F KingstonMahidol Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand.
Aniruddha GhoseDepartment of Medicine, Chittagong Medical College Hospital.
Thanaporn WattanakulMahidol Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand.
Md Mahtab Uddin HassanDepartment of Medicine, Chittagong Medical College Hospital.
Md Shafiul HaiderDepartment of Nephrology, Chittagong Medical College Hospital.
Prodip K DuttaDepartment of Nephrology, Chittagong Medical College Hospital.
Md Akhterul IslamRamu Upazilla Health Complex, Cox's Bazaar.
Shamsul AlamDepartment of Anesthesiology, Chittagong Medical College Hospital.
Selim Md JahangirDepartment of Pharmacology, Chittagong Medical College Hospital.
A S M ZahedDepartment of Medicine, Chittagong Medical College Hospital.
Md Abdus SattarDepartment of Medicine, Chittagong Medical College Hospital.
M A Hassan ChowdhuryDepartment of Medicine, Chittagong Medical College Hospital.
M Trent HerdmanMahidol Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand.
Stije J LeopoldMahidol Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand.
Haruhiko IshiokaMahidol Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand.
Kim A PieraMenzies School of Health Research, Charles Darwin University, Northern Territory, Australia.
Prakaykaew CharunwatthanaMahidol Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand.
Kamolrat SilamutMahidol Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand.
Tsin W YeoMenzies School of Health Research, Charles Darwin University, Northern Territory, Australia.
Sue J LeeMahidol Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand.
Mavuto MukakaMahidol Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand.
Richard J MaudeMahidol Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand.
Gareth D H TurnerMahidol Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand.
Md Abul FaizMalaria Research Group, and Dev Care Foundation, Dhaka, Bangladesh.
Joel TarningMahidol Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand.
John A OatesDepartment of Internal Medicine, Vanderbilt University School of Medicine, Nashville,Tennessee.
Nicholas M AnsteyMenzies School of Health Research, Charles Darwin University, Northern Territory, Australia.
Nicholas J WhiteMahidol Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand.
Nicholas P J DayMahidol Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand.
Md Amir HossainDepartment of Medicine, Chittagong Medical College Hospital.
L Jackson Roberts IiDepartment of Internal Medicine, Vanderbilt University School of Medicine, Nashville,Tennessee.
Arjen M DondorpMahidol Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand.
Chittagong Medical College · BDMahidol Oxford Tropical Medicine Research Unit · THMahidol University · THCharles Darwin University · AUUniversity of Oxford · GBVanderbilt University · USChild Health Research Foundation · BDHarvard University · US

Funding

THE PHARMACOLOGY OF INHIBITORS OF HEME PROTEIN-CATALYZED LIPID PEROXIDATIONP50GM015431 · NIGMS · VANDERBILT UNIVERSITY · PI ROBERTS, II, L JACKSON · 1985 to 2010
$15.0M
Therapeutic Modulation of Endothelial Cell TetrahydrobiopterinP01GM015431 · NIGMS · VANDERBILT UNIVERSITY · PI ROBERTS, II, L JACKSON · 2011 to 2015
$9.5M
NIGMS NIH HHS P01 GM015431NIGMS NIH HHS P50 GM015431Wellcome TrustWellcome Trust 089275/Z/09/Z
6 · The paper itself

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. Clinical Trials Registration: NCT01641289.

Indexed as

AcetaminophenAcute Kidney InjuryAdolescentAdultAnalgesics, Non-NarcoticAntimalarialsArea Under CurveArtesunateFemaleHumansMalaria, FalciparumMaleYoung AdultAcetaminophenAnalgesics, Non-NarcoticAntimalarialsArtesunate

Identifiers

PMID29538635
PMCPMC6137116
OpenAlexW2793979519

What Socratic holds

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LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.