To assess the course of paracetamol and oxidative metabolite formation and their correlation with miR-122 in a therapeutic paracetamol regime of 1000mg every 6 hours for a period of at least 5 consecutive days.
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
bijwerking van medicatie
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
In the patient group treated with paracetamol: Difference in pharmacokinetic
parameters of acetaminophen and six of its metabolites (APAP-Glc, APAP-Sul,
APAP-OMe, APAP-GSH, APAP-Cys, and APAP-Cys-NAC) following the administration of
paracetamol four times daily after 24 hours and 120 hours of treatment.
Secondary outcome
Secondary endpoints include the correlation between pharmacokinetic parameters
of APAP and metabolites and levels of MiR-122. Furthermore, miR-122 levels of
the patients treated with FICB and paracetamol will be compared with patients
who received FICB only.
Background summary
Paracetamol (APAP) is one of the most widely used drugs. Theoretically (frail)
older people are more susceptible for paracetamol hepatotoxicity due to age
related pharmacokinetic changes such as reduced clearance and decreased volume
of distribution, and lower capacity of glucuronidation and sulphation. However
whether these changes are clinically relevant for the present guideline advice
recommending 1,5 - 2,5 grams for chronic use remains unclear. Emerging
techniques measuring oxidative APAP metabolites and microRNA-122 (miR-122)
could make it possible to detect paracetamol induced liver injury earlier and
more precisely than currently used paracetamol plasma concentrations and
clinical chemical parameters such as alanine transaminase levels.
Study objective
To assess the course of paracetamol and oxidative metabolite formation and
their correlation with miR-122 in a therapeutic paracetamol regime of 1000mg
every 6 hours for a period of at least 5 consecutive days.
Study design
Open-label proof of concept pharmacokinetic study
Study burden and risks
Treatment with FICB and paracetamol is conform local peri-operative pain
regimen. The burden of this study solely consists of the additional
venepunctures that will be done. The total number of punctures is variable. For
the paracetamol group, this will be 15 vials (46.5ml) in 8 individual
venepunctures, depending on the route of paracetamol administration (orally of
intravenously). For the control group, this will be 4-8 vials (12-24ml) in 3-6
individual venepunctures, depending on when paracetamol is started (see table
1). It is estimated that patients will have standard of care venepunctures
twice in the 5 five post-operative days, thus the maximum number of additional
single punctures is 6 within one patient. However, the amount of additional
blood drawn is low, with a maximum total volume of 46,5ml. This amount is not
expected to have any negative consequences for the individual.
Heidelberglaan 100
Utrecht 3584 CX
NL
Heidelberglaan 100
Utrecht 3584 CX
NL
Listed location countries
Age
Inclusion criteria
- (Intended) admission to the geriatric trauma unit (OLVG West) (post-operative
acute hip fracture patients)
- Age >=70 years
- Received a Fascia Iliaca Compartiment Block (FICB) on admission on the ER
(hospital standard of care protocol acute hip fracture) or other adequate pain
medication
- Written informed consent by patient or witness when the patient is
analphabetic and oral consent is given or legal representative
Exclusion criteria
- Use of paracetamol in 72 hours prior to admission
- Known allergy or contra indication for use of paracetamol (i.e. severe liver
cirrhosis, G6PD deficiency)
- Abnormalities in AST / ALT / Bilirubin / gGT / ALP (> 2.5 x upper limit of
normal)
- Alcoholism (>= 2 units of alcohol per day)
- Difficulty in donating blood or limited accessibility of a vein
- Use of tobacco products (causing induction CYP1A2) in 7 days prior to
admission [27].
- Use of other CYP inducers/inhibitors which may have impact on acetaminophen
metabolism.
- Inability to understand and give informed consent due to (temporally)
incapacitation
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | Netherlands Trial Register onder nummer: NL9493 |
| CCMO | NL77760.041.21 |