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APAP Hepatotoxicity After Therapeutic Doses

NCT03602274 · Status: UNKNOWN · Type: OBSERVATIONAL · Enrollment: 96

Last updated 2018-07-26

No results posted yet for this study

Summary

Paracetamol (acetaminophen, APAP) is the most commonly used antipyretic and painkiller worldwide, but also the leading cause of acute liver failure (ALF) in developed countries after supra-therapeutic doses (half overdoses being unintentional). At therapeutic doses (4g/day), up to one third of healthy volunteers develop liver test elevation and cases of ALF have been described in the presence of suggested risk factors such as malnutrition, fasting and low body weight as a result of glutathione depletion. However, no well conducted study has aimed to prospectively assess the impact of malnutrition/fasting on the toxicity to therapeutic doses of APAP. Considering the widespread use of APAP and the prevalence of malnutrition in hospitalized patients (up to 30%), it is of crucial importance to assess whether these patients are at higher risk of hepatotoxicity. It is indeed likely that cases of liver damage secondary to normal recommended dose are under-estimated in these situations as the dose is not perceived as excessive and not described as such in international guidelines for pain management. The primary objective of our project will therefore be to assess if malnutrition and fasting are risk factors for liver toxicity after therapeutic doses (4g/day) of APAP in surgery patients. The second objective will be to evaluate the pharmacokinetics of APAP and metabolites according to nutrition status in order to establish, if necessary, dose reduction guidelines. Developing and validating an early and easily accessible marker of hepatotoxicity would especially be useful in these putative higher risk and fragile populations in order to improve early detection diagnosis and allow earlier management.

Conditions

Interventions

DIAGNOSTIC_TEST

Hepatic function monitoring

AST, ALT, GGT, AP, Bilirubin

DIAGNOSTIC_TEST

Nutritional status assesment

PINI, MNA nutritional assessment, PG-SGA assessment, anthropometric measurements

OTHER

Biomarker research sampling

Blood collection for proteomic, genetic, metabolomic and microRNA transcriptomic profiling

Sponsors & Collaborators

  • University Hospital, Geneva

    lead OTHER

Principal Investigators

  • Jules Desmeules, Prof. · HUG

  • Caroline Samer, MD · HUG

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2015-02-10
Primary Completion
2018-07-31
Completion
2018-12-31

Countries

  • Switzerland

Study Locations

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Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT03602274 on ClinicalTrials.gov