Clinical Trial Results:
THE USE OF ADV6209 FOR PREMEDICATION IN PAEDIATRIC ANAESTHESIA: A CONTROLLED, RANDOMIZED, DOUBLE BLINDED STUDY
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Summary
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EudraCT number |
2019-001853-25 |
Trial protocol |
AT |
Global end of trial date |
17 Sep 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
20 Oct 2022
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First version publication date |
20 Oct 2022
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Other versions |
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Summary report(s) |
Publication_ADV6209 |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
1.2-24.05.2019
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03931057 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Medical University Vienna
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Sponsor organisation address |
Spitalgasse 23, Vienna, Austria, 1090
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Public contact |
Dept. of Paediatric Anaesthesia, Medical University of Vienna, 0043 14040019227, peter.marhofer@meduniwien.ac.at
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Scientific contact |
Dept. of Paediatric Anaesthesia, Medical University of Vienna, 0043 14040019227, peter.marhofer@meduniwien.ac.at
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
17 Sep 2021
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
17 Sep 2021
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Global end of trial reached? |
Yes
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Global end of trial date |
17 Sep 2021
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the effect of ADV6209, a new oral Midazolam formulation, on preoperative anxiety and sedation levels in paediatric anaesthesia
Primary Objective: Sedation score (mYPAS) 30 min after administration of the premedication drug
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Protection of trial subjects |
All participants got premedication to minimize stress
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
17 Nov 2020
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Austria: 80
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Worldwide total number of subjects |
80
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EEA total number of subjects |
80
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
80
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The participants were recruited at the department of pediatric anaesthesia / surgery of the Medical University Vienna | |||||||||
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Pre-assignment
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Screening details |
90 participants were screened - 80 were enrolled, 10 were excluded because the parents / legal guardians denied the participation | |||||||||
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Period 1
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Period 1 title |
overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||
Roles blinded |
Subject, Investigator, Data analyst | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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ADV6209 | |||||||||
Arm description |
- | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Ozalin
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Investigational medicinal product code |
ADV6209
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Other name |
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Pharmaceutical forms |
Oral solution
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Routes of administration |
Oral use
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Dosage and administration details |
one single oral dose of 0.25 mg/kg
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Arm title
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Dormicum | |||||||||
Arm description |
- | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Dormicum
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Investigational medicinal product code |
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Other name |
Midazolam
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Oral use
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Dosage and administration details |
one single dose of 0.25 mg/kg
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Baseline characteristics reporting groups
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Reporting group title |
ADV6209
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Dormicum
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
all subjects
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
A Kolmogorov–Smirnov test was used to check for normal distribution, followed
by a non-parametric Mann–Whitney U-test for intergroup comparisons of metric and not normally distributed data, namely mYPAS-SF scores at baseline (i.e., before premedication)
and 30 min later (i.e., immediately before mask induction). Absolute differences between
both of these points in time was further categorized as (1) unchanged scores indicating no
effect, (2) higher scores indicating an unfavorable effect and (3) lower scores indicating
a favorable effect on anxiety. For intergroup comparisons of proportions, we used cross-
tabulation and the Pearson’s chi-square test. The chances of false-positive results (type I
errors) from multiple testing were reduced by Bonferroni correction, results expressed as
medians with interquartile ranges (IQRs) and/or absolute values with percentages and
differences considered significant atp< 0.05. All operations were performed with IBM®
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End points reporting groups
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Reporting group title |
ADV6209
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Reporting group description |
- | ||
Reporting group title |
Dormicum
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Reporting group description |
- | ||
Subject analysis set title |
all subjects
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
A Kolmogorov–Smirnov test was used to check for normal distribution, followed
by a non-parametric Mann–Whitney U-test for intergroup comparisons of metric and not normally distributed data, namely mYPAS-SF scores at baseline (i.e., before premedication)
and 30 min later (i.e., immediately before mask induction). Absolute differences between
both of these points in time was further categorized as (1) unchanged scores indicating no
effect, (2) higher scores indicating an unfavorable effect and (3) lower scores indicating
a favorable effect on anxiety. For intergroup comparisons of proportions, we used cross-
tabulation and the Pearson’s chi-square test. The chances of false-positive results (type I
errors) from multiple testing were reduced by Bonferroni correction, results expressed as
medians with interquartile ranges (IQRs) and/or absolute values with percentages and
differences considered significant atp< 0.05. All operations were performed with IBM®
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End point title |
Patient anxiety 30 min after the premedication | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
The primary endpoint of the study was patient anxiety 30 min after administration
of premedication, immediately before anesthesia induction, which was assessed as laid
out in the modified Yale Preoperative Anxiety Scale-Short Form (mYPAS-SF) [8] based on
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Statistical analysis title |
Mann Whitney U Test | ||||||||||||
Statistical analysis description |
Mann Whitney U Test
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Comparison groups |
ADV6209 v Dormicum
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Number of subjects included in analysis |
80
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Analysis specification |
Post-hoc
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Analysis type |
equivalence [1] | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Parameter type |
Median difference (final values) | ||||||||||||
Confidence interval |
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| Notes [1] - Anxiety scores obtained immediately prior to mask induction. This primary outcome parameter of the study did not reveal any statistical significance between the ADV6209 group and the conventional midazolam group. |
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Adverse events information [1]
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Timeframe for reporting adverse events |
overall trial
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Adverse event reporting additional description |
clinical observation during the study
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Assessment type |
Non-systematic | ||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||
Dictionary version |
19.0
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| Frequency threshold for reporting non-serious adverse events: 0% | |||
| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: No non-serious adverse event related to the study medications were recorded. |
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| We included only children scheduled for anesthesia induction via facemask in this analysis, which could be considered as a limitation of the current study. This decision was based on the fact that anesthesia induction via facemask in children from | |||
