The primary objective of this study will be to determine the pharmacokinetic profile of lorazepam oral liquid 1 mg/ml in the paediatric ICU population, with specific attention for the population aged up to 12 years of age.The secondary objectives…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
lichamelijke afhankelijkheid van een sedativum
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary aim of this study is to characterize the pharmacokinetic parameters
CL, Vd, Cmax, tmax, F and ka of lorazepam using the newly developed lorazepam
oral solution 1 mg/ml in infants and children
Secondary outcome
The secondary study parameters are:
- to explore the impact of clinical and genetic co-variates on pharmacokinetic
parameters,
- to evaluate the withdrawal protocol by monitoring occurrence of symptoms of
withdrawal with use of the Sophia Observation withdrawal Symptoms (SOS) scale,
- to assess acceptability and safety of the lorazepam liquid formulation.
Background summary
After prolonged use of sedative drugs at the paediatric intensive care unit,
children are switched to oral lorazepam in clinical practice, to prevent
withdrawal symptoms and facilitate tapering of the sedatives. The current
weaning guideline, including the conversion to equipotent lorazepam dosages,
has been derived from PK/PD data from adult patients and the impact of ontogeny
on the conversion has not yet been assessed. No standardised oral liquid
formulation of lorazepam has been available for use during weaning.
In this study we aim to generate pharmacokinetic data of lorazepam in children
to optimise the dose-conversion in the weaning guideline in different
age-groups, using a newly-developed standardised oral liquid formulation of
lorazepam.
Study objective
The primary objective of this study will be to determine the pharmacokinetic
profile of lorazepam oral liquid 1 mg/ml in the paediatric ICU population, with
specific attention for the population aged up to 12 years of age.
The secondary objectives are:
* to explore the impact of clinical co-variates on pharmacokinetic
parameters,
* to assess the occurrence of symptoms of withdrawal with use of SOS scale,
* to assess the occurrence of over- and undersedation with use of the
COMFORT-B scale and Nurses* Interpretation of Sedation Score.
* to use the observed pharmacokinetic data to optimize the current withdrawal
protocol,
* to assess the acceptability and safety of the lorazepam liquid formulation,
* to explore the impact of UGT2B15*2 SNP on pharmacokinetic variability.
Study design
Single center, cross-over, non-randomised, pharmacokinetic study
Intervention
All patients are switched to lorazepam according to current clinical practice.
The first dosage of lorazepam is administered intravenously, and the following
dosages are administered orally using the standardized lorazepam oral liquid.
Children currently treated with oral lorazepam are switch to study medication.
Study burden and risks
Lorazepam is given with therapeutic intent and all patient will be treated with
lorazepam in regular dosages, irrespectively of their participation in the
study. However, only in the study they will receive lorazepam as an oral liquid.
This new lorazepam oral solution is well validated and tailored to the specific
needs of the paediatric population including acceptable palatability, dose
flexibility, ease of administration and use of appropriate pharmaceutical
excipients.
The first dosage of lorazepam is administered intravenously in the study, in
order to obtain a full pharmacokinetic profile. The burden of this
administration will be minimal as an intravenous access will still be in place
and the lorazepam is administered with therapeutic intent. The subsequent oral
dosages will be administered as a standardised oral liquid, which replaces
individual extemporaneously prepared capsules or orally administered iv fluid,
both of which are not validated for this use. During both iv and oral use, 3
blood samples are drawn to determine blood levels of lorazepam. Blood sampling
will be combined with blood sampling for clinical care as much as possible. The
occurrence of withdrawal symptoms is monitored and treated as routine clinical
care.
All procedures are outweighed against the benefits of the study and the
availability of oral lorazepam liquid for the paediatric population.
Wytemaweg 80
Rotterdam 3015 CN
NL
Wytemaweg 80
Rotterdam 3015 CN
NL
Listed location countries
Age
Inclusion criteria
* aged below 12 years old,
* signed consent from the parent or legal assent,
* admitted to the Sophia Children's Hospital,
* scheduled to start the weaning protocol with oral lorazepam, or
* currently treated with lorazepam.
Exclusion criteria
* concomitant treatment with another investigational drug,
* contraindications for lorazepam use;
-Severe liver insufficiency, defined as 5 times upper level of ALAT and ASAT
-Hypersensitivity to lorazepam,
-Myasthenia gravis
Design
Recruitment
Medical products/devices used
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 |
|---|---|
| EudraCT | EUCTR2015-001043-37-NL |
| CCMO | NL53014.078.15 |