Paediatric accelerator mass spectrometry evaluation research study

ISRCTN ISRCTN24569018
DOI https://doi.org/10.1186/ISRCTN24569018
Secondary identifying numbers 1.0
Submission date
22/10/2012
Registration date
27/11/2012
Last edited
24/01/2017
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Other
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Background and study aims
There is an urgent need to ensure that medicines given to children are assessed sufficiently. A range of methods have been proposed to do this. The aim of the study is to apply and test a method called microtracer dosing with accelerator mass spectrometry (AMS) bioanalysis, using paracetamol as a model drug and find out its effects on newborn, infants and toddlers. The results are compared with the information available in previous research that used standard methods. This study could establish a way for AMS studies to be a part of Paediatric Investigation Plans for development of new drugs. This will mean that new drugs can be given to children earlier than in current practice.

Who can participate?
Male and female hospitalised infants aged between preterm up to 2 years

What does the study involve?
A single microdose of radioactive paracetamol will be given to infants whose age range is preterm up to 2 years of age orally or injected through the vein. A maximum of 20 extra drops of blood is taken from each participant. This is spread over the 12 hours after the isotope dose is received. The total amount of blood taken will be 1ml. The blood is taken via the lines already in place. The maximum length of participation in the study is up to 48 hours after giving the study drug.

What are the possible benefits and risks of participating?
The participants will not gain any direct benefit. The benefits from this study are for other babies in the future as the information gathered in this study becomes available. The risks due to paracetamol will be minimal as this microdose is less than a millionth of the dose normally given to newborn babies and infants. There are no anticipated safety issues relating to exposure to the radioactive drug.

Where is the study run from?
1. Liverpool Women’s NHS Foundation Trust, UK (lead centre)
2. Tartu University Hospital, Children’s Clinic, Estonia
3. Alder Hey Children’s NHS Foundation Trust, UK

When is the study starting and how long is it expected to run for?
The study started in November 2012 and will run for 2 years.

Who is funding the study?
ERA-NET PrioMedChild (Priority Medicines for Children), Netherlands.

Who is the main contact?
Miss Louise Hardman
louise.hardman@lwh.nhs.uk

Contact information

Dr Mark Turner
Scientific

Liverpool Women's NHS Foundation Trust
Crown Street
Liverpool
L8 7SS
United Kingdom

Phone +44 (0)151 795 9558
Email mark.turner@liverpool.ac.uk

Study information

Study designMulticentre observational open-label study
Primary study designObservational
Secondary study designNon randomised controlled trial
Study setting(s)Hospital
Study typeOther
Participant information sheet Not available in web format, please use the contact details to request a patient information sheet
Scientific titleA multi-centre clinical study to evaluate the use of a microtrace dose of 14C-labelled paracetamol and Accelerator Mass Spectrometry (AMS) bioanalysis as new tools in drug development to determine pharmacokinetics in neonates, infants and toddlers
Study acronymPAMS
Study objectives14C-labelled microdose paracetamol has similar PK to standard, therapeutic paracetamol.
Ethics approval(s)NRES Committee North West - Liverpool East, 08/10/2012, ref: 12/NW/0675
Health condition(s) or problem(s) studiedMedicines for Children; Paediatrics
InterventionNo specific study-related assessments will be conducted.

No haematology, biochemistry or blood gas studies samples will be taken for the purposes of this study. The most recent blood samples will be included in the data if they are taken 24 hours before the drug is administered in neonates and up to 3-7 days before for older infants. A maximum of 5 blood samples after drug administration will also be collected. Details of blood results that will be collected for the study data are:

Biochemistry: Plasma creatinine, Na+, K+ Cl, AST, ALT, alkaline phosphatase, total bilirubin, conjugated bilirubin, albumin, total calcium, corrected calcium, magnesium, C-reactive protein.
Full Blood Count: Hgb, total white cell count, differential white cell count, MCV, MCH, MCHC and platelets.
Blood gas: pH, glucose, lactate, ionized calcium

In participants with urinary catheters in place the urine collection bag will be emptied immediately before the microdose is administered. Timed samples of urine will be collected for 48 hours after the microdose is administered.
Intervention typeOther
Primary outcome measureA noncompartmental model of paracetamol disposition
Secondary outcome measuresA population model of the whole dataset taking account of all the variables
Overall study start date12/11/2012
Completion date11/11/2014

Eligibility

Participant type(s)Patient
Age groupMixed
SexBoth
Target number of participants60
Key inclusion criteria1. Infants and toddlers from preterm neonates (32-36 GW at birth) up to 2 years of age
2. Having intravenous or intra-arterial access suitable for blood sampling
3. Written informed consent prior to any study-specific procedures
4. Able to tolerate oral administration for oral administration group
Key exclusion criteria1. History of allergy or hypersensitivity to paracetamol;
2. Serious hepatic and/or renal impairment defined as creatinine > 150 micromol or AST or ALT > 200
3. Be otherwise unsuitable for the study, in the opinion of the investigator
4. Extracorporeal membrane oxygenation (ECMO)
5. Haemofiltration, peritoneal dialysis, haemodialysis
Date of first enrolment12/11/2012
Date of final enrolment11/11/2014

Locations

Countries of recruitment

  • England
  • Estonia
  • United Kingdom

Study participating centre

Liverpool Women's NHS Foundation Trust
Liverpool
L8 7SS
United Kingdom

Sponsor information

Liverpool Women's NHS Foundation Trust (UK)
Hospital/treatment centre

Crown Street
Liverpool
L8 7SS
England
United Kingdom

Phone +44 (0)151 702 4346
Email research@lwh.nhs.uk
Website http://www.liverpoolwomens.nhs.uk/
ROR logo "ROR" https://ror.org/04q5r0746

Funders

Funder type

Research organisation

ERA-NET PrioMedChild (Priority Medicines for Children) (Netherlands)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 01/07/2015 Yes No

Editorial Notes

24/01/2017: Publication reference added.