Ignite Creation Date:
2024-05-06 @ 2:27 AM
Last Modification Date:
2024-10-26 @ 11:18 AM
Study NCT ID:
NCT02040909
Status:
TERMINATED
Last Update Posted:
2018-02-01
First Post:
2013-12-23
Brief Title:
Optimizing Propofol Dosing for Preterm Newborn Infants That Need Endotracheal Intubation
Sponsor:
Erasmus Medical Center
Organization:
Erasmus Medical Center
Study Overview
Official Title:
Optimizing Propofol Dosing for Preterm Newborn Infants That Need Endotracheal Intubation
Status:
TERMINATED
Status Verified Date:
2018-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
interim results concluded no added value of additional inclusion
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
NEOPROP2
Brief Summary:
Newborns admitted to an intensive care unit often require artificial ventilation For that purpose an endotracheal tube needs to be placed into the trachea a procedure named endotracheal intubation The newborns need to be sedated to keep them comfortable to stop moving and to relax in order to enable the success of the procedure For this sedation an anesthetic agent named propofol is often used The used dose of propofol has not been properly studied and as a consequence patients are under- or over -sedated and propofol leads to side effects such as hypotension
The current study aims to find the most appropriate dose of propofol for newborns of different gestational ages and of different post-natal ages We will use propofol in different doses and after each 5 included patients per age group we will analyze whether the dose needs to be increased or decreased The effect of the propofol will be extensively monitored and we will study the level of sedation the quality of intubation the stability of the patient en the occurrence of side effects
At the end we aim to have appropriate guidelines for propofol doses in newborns of all ages
The current study aims to find the most appropriate dose of propofol for newborns of different gestational ages and of different post-natal ages We will use propofol in different doses and after each 5 included patients per age group we will analyze whether the dose needs to be increased or decreased The effect of the propofol will be extensively monitored and we will study the level of sedation the quality of intubation the stability of the patient en the occurrence of side effects
At the end we aim to have appropriate guidelines for propofol doses in newborns of all ages
Detailed Description:
Rationale Propofol a rapidly acting anaesthetic agent is currently used unlicensed in the clinical care of preterm neonates as sedative for endotracheal intubation Neonates receive the same propofol doses per kg bodyweight independent of their developmental stage gestational age postnatal age morbidity co-medication etc This is related to a high failure rate of intubation attempts and leads to hypotension in around 40 percent of patients Propofol research in newborn infants is on the recently published priority drug research list of the European Medicines Agency EMA Propofol metabolism and elimination PK pharmacokinetics as well as propofol effects PD pharmacodynamics highly depend on the stage of development and on the genetic make-up of a patient This study is based on the hypotheses that currently used single doses of propofol for newborn infants can be optimized and that this will improve the quality of sedation and increase the safety of the patients
Objective To determine effective and safe age specific propofol dosing guidelines for neonates of different age groups both gestational age and postnatal age Secondary objective is to determine a new age specific PKPD pharmacokineticpharmacodynamic including a specific propofol genotype pharmacogenetic analyses that enables much better prediction of the effects and side-effects of propofol
Study design Prospective single dose optimizing and dose validation study
Study population Neonates admitted at the Neonatal Intensive Care Unit gestational age 24 - 42 weeks post natal age 28 days divided into 8 different age groups that need semi-elective endotracheal intubation
Intervention if applicable Adapted propofol dose Starting dose is dependent on effects of previously included patients Dose is increased in case of insufficient sedation Intubation is started only after sedation level is adequate titration with additional propofol is possible because propofol is very fast acting
Main study parametersendpoints Primary outcome is the appropriate dose of propofol in 8 different age groups Optimized propofol doses need to be related with adequate sedation good quality of intubation conditions and no short term side effects Secondary endpoints include further evaluation of cerebral perfusion stress levels and short and long term outcome of the included patients The incorporation of PK data and genotype of patients is used to make a prediction model for future patients that includes various important cofactors related to effects and side effects of propofol Physiological and behavioural responses of the newborns are further explored to find the most reliable and validate neonatal sedation score for intubations
Nature and extent of the burden and risks associated with participation benefit and group relatedness
Propofol is used as a standard of care for sedation before intubation in newborn infants Drug metabolism drug transporters and drug receptors are not yet well developed in preterm newborn infants Therefore PKPD is very much dependent on the developmental stage of the newborn infant and though changes with age This study can therefore not be done in another patient group for instance older patients or healthy volunteers
Internationally used propofol starting doses in newborns vary between 10 to 25 mgkg and are repeated if necessary The current study will start with propofol doses of 10 mgkg in every age group If the study starting dose is insufficient the patient will receive additional propofol doses 10 mgkg until adequate sedation is acquired No patient will be intubated before adequate sedation is reached This is possible because propofol is very fast acting 1-2 minutes
If the starting dose turns out to be insufficient in 5 patients per group it will be increased in the following patients of that group The effect of an initial propofol dose is tested to find the optimal propofol doses for neonates in different developmental stages The study will be continued until the appropriate dose for each age group is determined The appropriate doses are re-used in another 5 patients per age group to validate the predetermined doses Safety is monitored very intensively and if hypotension occurs this is immediately treated The patient will benefit from this intensive safety monitoring because side-effects will be detected earlier and can be more effectively treated
Included patients will be monitored with non-invasive techniques videotaping cranial ultrasound aEEG NIRS next to the standard intensive care monitoring of physiological parameters
Blood samples will only be collected from indwelling arterial lines or during routine blood sampling because of normal patients care An amount of 17 ml blood 05 ml for DNA analyses 2 times 06 ml for propofol PK analyses is taken if possible Two saliva samples for cortisol analyses will be collected
Objective To determine effective and safe age specific propofol dosing guidelines for neonates of different age groups both gestational age and postnatal age Secondary objective is to determine a new age specific PKPD pharmacokineticpharmacodynamic including a specific propofol genotype pharmacogenetic analyses that enables much better prediction of the effects and side-effects of propofol
Study design Prospective single dose optimizing and dose validation study
Study population Neonates admitted at the Neonatal Intensive Care Unit gestational age 24 - 42 weeks post natal age 28 days divided into 8 different age groups that need semi-elective endotracheal intubation
Intervention if applicable Adapted propofol dose Starting dose is dependent on effects of previously included patients Dose is increased in case of insufficient sedation Intubation is started only after sedation level is adequate titration with additional propofol is possible because propofol is very fast acting
Main study parametersendpoints Primary outcome is the appropriate dose of propofol in 8 different age groups Optimized propofol doses need to be related with adequate sedation good quality of intubation conditions and no short term side effects Secondary endpoints include further evaluation of cerebral perfusion stress levels and short and long term outcome of the included patients The incorporation of PK data and genotype of patients is used to make a prediction model for future patients that includes various important cofactors related to effects and side effects of propofol Physiological and behavioural responses of the newborns are further explored to find the most reliable and validate neonatal sedation score for intubations
Nature and extent of the burden and risks associated with participation benefit and group relatedness
Propofol is used as a standard of care for sedation before intubation in newborn infants Drug metabolism drug transporters and drug receptors are not yet well developed in preterm newborn infants Therefore PKPD is very much dependent on the developmental stage of the newborn infant and though changes with age This study can therefore not be done in another patient group for instance older patients or healthy volunteers
Internationally used propofol starting doses in newborns vary between 10 to 25 mgkg and are repeated if necessary The current study will start with propofol doses of 10 mgkg in every age group If the study starting dose is insufficient the patient will receive additional propofol doses 10 mgkg until adequate sedation is acquired No patient will be intubated before adequate sedation is reached This is possible because propofol is very fast acting 1-2 minutes
If the starting dose turns out to be insufficient in 5 patients per group it will be increased in the following patients of that group The effect of an initial propofol dose is tested to find the optimal propofol doses for neonates in different developmental stages The study will be continued until the appropriate dose for each age group is determined The appropriate doses are re-used in another 5 patients per age group to validate the predetermined doses Safety is monitored very intensively and if hypotension occurs this is immediately treated The patient will benefit from this intensive safety monitoring because side-effects will be detected earlier and can be more effectively treated
Included patients will be monitored with non-invasive techniques videotaping cranial ultrasound aEEG NIRS next to the standard intensive care monitoring of physiological parameters
Blood samples will only be collected from indwelling arterial lines or during routine blood sampling because of normal patients care An amount of 17 ml blood 05 ml for DNA analyses 2 times 06 ml for propofol PK analyses is taken if possible Two saliva samples for cortisol analyses will be collected
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 1201-020 | OTHER_GRANT | fondsNutsOhra | None |
| 2013-005572-17 | EUDRACT_NUMBER | None | None |
| 90713494 | OTHER_GRANT | None | None |