Clinical Trial Results:
Exploratory Propofol Dose Finding Study In Neonates receiving a single intravenous propofol bolus for endotracheal intubation during (semi-) elective INSURE (intubation-surfactant-extubation) procedure (preterm neonates) and (semi-)elective non-INSURE procedures (term-preterm neonates). NEOPROP.
Summary
|
|
EudraCT number |
2012-002648-26 |
Trial protocol |
BE |
Global end of trial date |
17 Jul 2014
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
19 Dec 2024
|
First version publication date |
19 Dec 2024
|
Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
Trial identification
|
|||
Sponsor protocol code |
S54472
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT01621373 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
|
|||
Sponsor organisation name |
University Hospitals Leuven
|
||
Sponsor organisation address |
Herestraat 49, Leuven, Belgium, 3000
|
||
Public contact |
Liesbeth Thewissen, University Hospitals Leuven, +32 16343211, Liesbeth.thewissen@uzleuven.be
|
||
Scientific contact |
Liesbeth Thewissen, University Hospitals Leuven, +32 16343211, Liesbeth.thewissen@uzleuven.be
|
||
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
01 Aug 2016
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
17 Jul 2014
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
17 Jul 2014
|
||
Was the trial ended prematurely? |
No
|
||
General information about the trial
|
|||
Main objective of the trial |
-What is the most effective intravenously (iv) administered single propofol dose for successful INSURE prodecure in neonates? INSURE-procedure is defined as (semi-)elective intubation, intratracheal administration of surfactant and extubation within 60 minutes after propofol administration.
-What is the most effective intravenously (iv) administered single propofol dose for successful (semi-)elective intubation of neonates during non-INSURE conditions (e.g. surgery)?
|
||
Protection of trial subjects |
Neonates of the University Hospitals Leuven needing
preintubation sedation were included after consent from their
parents was obtained. Patients had to be hemodynamically
stable and not receiving sedatives or analgesics (except acetaminophen)
in the previous 24 hours.
|
||
Background therapy |
It is standard of care to give premedication before (semi-)elective intubation in neonates. Drug selection and dosing for this procedure is highly variable and not yet evidence-based. One of the compounds used is propofol, a short-acting anesthetic. Postmenstrual age (PMA) and postnatal age (PNA) have been shown to affect propofol clearance,4 but pharmacodynamic (PD) data in neonates are limited. Because optimal propofol dosing and its PD effects in newborns are lacking, we combined a prospective dose-finding approach with PD assessment in neonates receiving propofol as intravenous bolus for preintubation sedation (The Exploratory Propofol Dose-Finding Study In Neonates [NEOPROP] study). The primary objective was to define the ED50 (ie, effective dose for 50% of patients) for successful intubation and to determine the rate of successful extubation in those patients with planned intubation, surfactant administration, and immediate extubation12,13 (INSURE procedure). | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Jul 2012
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Belgium: 47
|
||
Worldwide total number of subjects |
47
|
||
EEA total number of subjects |
47
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
47
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
0
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
|
|||||||||||||
Recruitment
|
|||||||||||||
Recruitment details |
Neonates of the University Hospitals Leuven needing preintubation sedation were included after consent from their parents was obtained. | ||||||||||||
Pre-assignment
|
|||||||||||||
Screening details |
Patients had to be hemodynamically stable and not receiving sedatives or analgesics (except acetaminophen) in the previous 24 hours. | ||||||||||||
Period 1
|
|||||||||||||
Period 1 title |
ED 50 calculation propofol (overall period)
|
||||||||||||
Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Not applicable
|
||||||||||||
Blinding used |
Not blinded | ||||||||||||
Arms
|
|||||||||||||
Are arms mutually exclusive |
Yes
|
||||||||||||
Arm title
|
Stratum 1 | ||||||||||||
Arm description |
Postmenstrual age < 28 w Postnatal age < 10 days | ||||||||||||
Arm type |
Stratum 1 | ||||||||||||
Investigational medicinal product name |
Propofol
|
||||||||||||
Investigational medicinal product code |
|||||||||||||
Other name |
|||||||||||||
Pharmaceutical forms |
Concentrate for emulsion for injection
|
||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||
Dosage and administration details |
up and down dose-response design
|
||||||||||||
Arm title
|
Stratum 3 | ||||||||||||
Arm description |
Postmenstrual age 28 to <32 w Postnatal age < 10 days | ||||||||||||
Arm type |
Stratum 3 | ||||||||||||
Investigational medicinal product name |
Propofol
|
||||||||||||
Investigational medicinal product code |
|||||||||||||
Other name |
|||||||||||||
Pharmaceutical forms |
Solution for injection
|
||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||
Dosage and administration details |
Up-)and-down dose-response design
|
||||||||||||
Arm title
|
Stratum 5 | ||||||||||||
Arm description |
Postmenstrual age 32 to <37 w Postnatal age < 10 days | ||||||||||||
Arm type |
Stratum 5 | ||||||||||||
Investigational medicinal product name |
Propofol
|
||||||||||||
Investigational medicinal product code |
|||||||||||||
Other name |
|||||||||||||
Pharmaceutical forms |
Solution for injection
|
||||||||||||
Routes of administration |
Intravenous bolus use
|
||||||||||||
Dosage and administration details |
Up-and-down dose-response design
|
||||||||||||
|
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
ED 50 calculation propofol
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Stratum 1
|
||
Reporting group description |
Postmenstrual age < 28 w Postnatal age < 10 days | ||
Reporting group title |
Stratum 3
|
||
Reporting group description |
Postmenstrual age 28 to <32 w Postnatal age < 10 days | ||
Reporting group title |
Stratum 5
|
||
Reporting group description |
Postmenstrual age 32 to <37 w Postnatal age < 10 days |
|
|||||||||||||||||
End point title |
Effective dose for 50% of patients for Succesful intubation and subsequent extubation in case of planned extubation after INSURE procedure | ||||||||||||||||
End point description |
An up-and-down dose-response design was used to calculate ED50 (mg/kg) in strata with effective sampling size of at least 6, by use of the Dixon-Massey method for small samples.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
1 hour after propofol administration
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Propofol ED50 Calculation | ||||||||||||||||
Statistical analysis description |
An up-and-down dose-response design was used to calculate
ED50 (mg/kg) in strata with an effective sampling size (N) of
at least 6, by use of the Dixon-Massey method14 for small
samples. N is the number of trials reduced by 1 less than the
number of similar responses at the beginning. ED50 = ∑Xi/
N + d(A + C)/N, with Xi: initial dose, d: interval between dose
levels (0.5 mg/kg) and A, C: tabulated values provided by
Dixon.14 SAS 9.2 for Windows (SAS Institute, Inc, Cary, North
Carolina)
|
||||||||||||||||
Comparison groups |
Stratum 1 v Stratum 3 v Stratum 5
|
||||||||||||||||
Number of subjects included in analysis |
47
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other [1] | ||||||||||||||||
P-value |
< 0.05 | ||||||||||||||||
Method |
up-and-down dose response | ||||||||||||||||
Parameter type |
ED50 | ||||||||||||||||
Point estimate |
0.5
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.5 | ||||||||||||||||
upper limit |
4 | ||||||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||||||
Dispersion value |
0.5
|
||||||||||||||||
Notes [1] - An up-and-down dose-response design was used to calculate ED50 (mg/kg) in strata with an effective sampling size (N) of at least 6, by use of the Dixon-Massey method14 for small samples. N is the number of trials reduced by 1 less than the number of similar responses at the beginning. ED50 = ∑Xi/ N + d(A + C)/N, with Xi: initial dose, d: interval between dose levels (0.5 mg/kg) and A, C: tabulated values provided by Dixon.14 SAS 9.2 for Windows (SAS Institute, Inc, Cary, North Carolina) |
|
|||||||||||||||||
Adverse events information
|
|||||||||||||||||
Timeframe for reporting adverse events |
not specified
|
||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||
Dictionary name |
neonatal | ||||||||||||||||
Dictionary version |
1
|
||||||||||||||||
Reporting groups
|
|||||||||||||||||
Reporting group title |
ED50
|
||||||||||||||||
Reporting group description |
- | ||||||||||||||||
|
|||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported | |||
Online references |
|||
http://www.ncbi.nlm.nih.gov/pubmed/27597733 |