E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Sedation for endotracheal intubation in newborns of different ages at the
neonatal intensive care unit |
Sedatie voor endotracheale intubatie bij pasgeborenen van verschillende leeftijden op de neonatale intensive care |
|
E.1.1.1 | Medical condition in easily understood language |
Critically ill newborn babies that need to artificial ventilation are
evaluated during the procedure where the tube for ventilation is
inserted. |
Ernstig zieke pasgeborenen die een beademingsbuisje nodig hebben op de intensive care |
|
E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10029392 |
E.1.2 | Term | Newborn |
E.1.2 | System Organ Class | 100000004869 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the most adequate age specific propofol doses for
neonates of different ages (both gestational age and postnatal age).
Adequate propofol doses are determined by 3 co-primary outcome
variables:
- Adequate sedation
- Optimal intubation conditions
- No hypotension or other severe side effects |
Het vaststellen van de meest adequate leeftijdspecifiekepropofol doseringen voor pasgeborenen
De adequate dosis zal worden bepaald afhankelijk van:
- goede sedatie
-goede intubatieconditie
- geen hypotensie of andere ernstige bijwerkingen |
|
E.2.2 | Secondary objectives of the trial |
- To develop a validated and useful sedation assessment instrument for
(preterm) newborns during endotracheal intubation. For this aim
validated pain assessment instruments will be compared with an
available sedation score by the use of videotapes. Furthermore we
aim to determine the relationship between these pain and sedation
scores with the patients stress level as measured by cortisol levels.
- To determine a new age specific PK/PD
(pharmacokinetic/pharmacodynamic) model for propofol.
Pharmacodynamic data of propofol are explored (duration of intubation,
duration of sedation, time of side effect, recovery of spontaneous
breathing). We will analyze propofol concentrations in a
|
- een gevalideerde en bruikbare sedatieschaal bepalen
- een leeftijdsafhankeleijk PK/PD model voor propofol
- exploratie van het propofol genotype
- exploratie van de hemodynamische effecten van propofol |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
All neonates admitted to the participating intensive care units:
- Less than 28 days postnatal age
- Who need endotracheal intubation |
Alle pasgeborenen opgenomen op de deelnemende neonatale intensive care afdelingen dei
minder dan 28 dagen oud zijn en
die een endotracheale intubatie moeten ondergaan |
|
E.4 | Principal exclusion criteria |
Patients with:
- Major congenital anomalies or neurological disorders,
- Neonates with an abnormal upper airway,
- Those receiving continuous sedatives or opioids, and
- Those whose mothers received sedatives or opioids before or during
delivery will be excluded during the first 2 days of life
- Those who previously participated in the study |
- Pasgeborenen met afwijkende bovenste luchtwegen,
- die continue sedativa of opiaten krijgen, en
- die wiens moeders sedativa of opiaten kregen voor of tijdens de bevalling zullen de eerste 2 dagen na de partus worden geexcludeerd
- zij die reeds eerder meededen aan de studie |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The main study endpoint in this study is the optimal dose of propofol for
each age group of newborns. The optimal dose of propofol is determined
by 3 outcome variables: level of sedation, quality of intubation and
sideeffects.
The optimal dose as determined in the first phase (phase A) of our study
will be validated in the 2nd part of our study (phase B). |
Leeftijdspecifieke propofol dosis richtlijnen |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
After every 5 patients per age group have been included the 3 primary
outcome measures of those 5 patients are evaluated and analysed. The
result of that analyses will determine the dose of propofol for the next 5
patients of the that specific age category. If the used dose in the 5
patients results in adeqaute sedation, good intubation conditions and no
hypotension or other clinically significant side effect the dose is
evaluated as appropriate. This will be re-evaluated in another 5 patients
of the same age to validate the dose and to determine it as optimal
propofol single dose for that age category. |
Na elke 5 geincludeerde patienten per groep zal een tussen analyse plaatsvinden om te analyseren of de dosis optimaal is |
|
E.5.2 | Secondary end point(s) |
A secondary endpoint of this study is the development of a validated and
useful sedation assessment instrument for (preterm) newborns during
endotracheal intubation. For this endpoint validated pain assessment
instruments (COMFORTneo, nPASS, PIPP and NIPS) will be compared
with an available sedation score[31] by the use of videotapes. The
validity of the sedation scores is determined by comparison with saliva
cortisol levels.
An age specific PK/PD (pharmacokinetic/pharmacodynamic) model for propofol is created by evaluation of propofol blood levels and
incorporation into a non-lineair-mixed effects modeling (NONMEM)
analyses.
Genotypic explanations for inter-individual variability in propofol
concentrations and effects of propofol by determination of variability in
genes encoding propofol metabolizing enzymes (UGT 1A9 and CYP 2B6)
and GABA receptors. |
- Een gevalideerd en bruikbaar instrument om sedatie te meten bij pasgeborenen tijdens intubatie
- Een farmacokinetiek/farmacodynamiek model voor neonatal propofol
- Vaststellen relatie genotype en fenotype voor propofol
- Vaststellen effecten van propofol op cerebrale perfusie |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
End of study |
Einde van de studie |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Dosis optimalisatie middels step-up en step-down design |
Dose optimaizing study with step-up and step-down design |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |