1. Study identification
EU PAS Register NumberEUPAS3276
Official titleACUTE AND CHRONIC ACETAMINOPHEN OVERDOSE IN PEDIATRIC POPULATION: PROSPECTIVE STUDY OF COHORT TO EVALUATE CLINIC FACTORS AND BIOMARKERS TO PREDICT DEVELOPMENT OF HEPATOTOXICITY/SOBREDOSIS AGUDA Y CRÓNICA DE PARACETAMOL EN POBLACIÓN PEDIÁTRICA: ESTUDIO PROSPECTIVO DE COHORTES PARA EVALUAR LOS FACTORES CLINICOS Y BIOMARCADORES PREDICTORES DE HEPATOTOXICIDAD
Study title acronymGEIPA-2012-01
Study typeObservational study
Brief description of the studyAcetaminophen is the main drug causing acute liver failure in some countries like the United States, UK and other European countries. Acetaminophen hepatotoxicity generally does not appear until several hours and even days after intake, which makes the detection of liver damage often delayed. One reason is that there is not available a biomarker of liver damage efficient to detect liver damage in early stages. The development of acetaminophen toxicity biomarkers could have important clinical implications for groups of patients who can not apply the Rumack-Matthew nomogram; e.g. arrive to the hospital at a late stage (> 24 hours after ingestion), chronic ingestion of acetaminophen, acute ingestion in alcoholic patients, concomitant intake of other drugs which could change the kinetics of acetaminophen and intake of sustained release of acetaminophen. The identification of new biomarkers that are specific to acetaminophen intoxication could be useful in the evaluation of children with acute liver failure of unknown etiology, in addition to predict the occurrence of liver damage in its early stage. Objectives of this study are 1.-To determine the clinical factors and biomarkers (pharmacokinetic, genetic and metabonomics) that predict the development of hepatotoxicity in paediatric population following acute and chronic intake of acetaminophen and 2.- Develop a predictive model to assess the risk of hepatotoxicity in acute and chronic intoxication by acetaminophen suited to paediatric patients for use in clinical practice.
Was this study requested by a regulator?No
Is the study required by a Risk Management Plan (RMP)?
Not applicable
Regulatory procedure number (RMP Category 1 and 2 studies only)
Other study registration identification numbers and URLs as applicable
2. Research centres and Investigator details
Coordinating study entity
Department/Research groupClinical Pharmacology Department
Organisation/affiliationHospital La Paz, School of Medicine, UAM
Details of (Primary) lead investigator
Title Dr
Last name Ramirez
First name Elena
Is this study being carried out with the collaboration of a research network?
No
Other centres where this study is being conducted
Multiple centres
In total how many centres are involved in this Study?4
Hospital Universitario "La Paz", Madrid, Spain
Hospital Universitario "Gregorio Marañón", Madrid, Spain
Hospital Universitario "Niño Jesús", Madrid, Spain
Hospital Universitario "12 de Octubre", Madrid, Spain
Countries in which this study is being conducted
National study
Spain
3. Study timelines: initial administrative steps, progress reports and final report
PlannedActual
Date when funding contract was signed15/01/2013
Start date of data collection30/01/2013
Start date of data analysis01/06/2018
Date of interim report, if expected
Date of final study report30/09/2020
4. Sources of funding
Please provide estimates of the percentage of funding by source for this study
Names(s)Approximate % funding
Pharmaceutical companies
Charities
Government body
Research councils
EU funding scheme
OtherClinical Pharmacology Department, HULP, UAM100
5. Contact details for enquiries
Scientific Enquiries
Title Dr
Last name Ramírez García
First name Elena
Address line 1Paseo de la Castellana Nº 261
Address line 2Clinic Pharmacology Department of La Paz University Hospital.
Address line 3
CityMadrid
Postcode28046
CountrySpain
Phone number (incl. country code)34-917277215
Alternative phone number34-917277559
Fax number (incl. country code)34-917277559
Public Enquiries
Title Dr
Last name Ramírez García
First name Elena
Address line 1Paseo de la Castellana Nº 261
Address line 2Clinic Pharmacology Department of La Paz University Hospital.
Address line 3
CityMadrid
Postcode28046
CountrySpain
Phone number (incl. country code)34-917277215
Alternative phone number34-917277559
Fax number (incl. country code)34-917277559
6. Study drug(s) information
Substance class (ATC Code)N02BE01 (paracetamol)
7. Medical conditions to be studied
Medical condition(s)Yes
Hepatotoxicity
8. Population under study
Age
Infants and toddlers (28 days - 23 months)
Children (2 - 11 years)
Adolescents (12 - 17 years)
Sex
Male
Female
9. Number of subjects
Estimated total number of subjects180
Additional information
36 cases
144 controls:
• Patients who have not taken acetaminophen in the past two weeks
• Patients with acetaminophen intake with no risk factors at dose recommended by the Pediatric Emergency guideline: 10-15 mg / kg / dose or 50-75 mg / kg / day for at least 5 doses of continuous dosing in 3 days (+ / - 1).
10. Source of data
Is this study being carried out with an established data source?No
Sources of data
Prospective patient-based data collection
11. Scope of the study
What is the scope of the study?
Risk assessment
Biomarkers detection, pharmacokinetics
Primary scope : Biomarkers detection, pharmacokinetics
12. Main objective(s)
What is the main objective of the study?
1. To determine the clinical factors and biomarkers (pharmacokinetic, genetic and metabonomics) that predict the development of hepatotoxicity in paediatric population following acute and chronic intake of acetaminophen.
2. Develop a predictive model to assess the risk of hepatotoxicity in acute and chronic intoxication by acetaminophen suited to paediatric patients for use in clinical practice
Are there primary outcomes?No
Are there secondary outcomes?No
13. Study design
What is the design of the study?
Cohort study
Pharmacokinetic study
Pharmacogenetics, metabonomics
14. Follow-up of patients
Will patients be followed up?Not applicable/no follow-up
15. Data analysis plan
Please provide a brief summary of the analysis method
To estimate differences between variables are used chi-square or T student if parametric. And if it does not follow a normal distribution, nonparametric tests will be used. To determine the factors associated with liver damage will design a multivariate logistic regression where the dependent variable is the presence of hepatotoxicity and a multivariate linear regression to determine the relationship between transaminase values and factors (demographic, clinical, kinetic, analytical, genetic and metabonómics).