The Use of ADV6209 for Premedication in Pediatric Anesthesia

February 15, 2022 updated by: Peter Marhofer, Medical University of Vienna

The Use of ADV6209 for Premedication in Pediatric Anesthesia: a Controlled, Randomized, Double Blinded Study

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 Secondary Objective: Acceptance of anaesthesia mask induction Acceptance of oral administration of the premedication drug

Study Overview

Status

Completed

Conditions

Preanesthetic Medication

Intervention / Treatment

Detailed Description

Premedication represents an important part in the perioperative management of children and is used to reduce pre-operative stress as well as to facilitate induction of inhaled anaesthesia. Midazolam is the drug most often used for premedication in infants and children because it provides good sedation, anxiolytic and amnestic effects and few side effects. Oral intake of the drug is the most preferred route of administration by paediatric patients, whereas the majority of existing oral Midazolam solutions involve the use of i.v. Midazolam formulation given orally, unregistered or off-label. Moreover i.v. Midazolam solutions are often not well accepted by children because of their bitter taste. Considering the lack of available oral medications for moderate sedation in children in most European countries, ADV6209, an innovative 0.2% (w/v) oral solution of Midazolam for children from six months of age, was developed. The formation of a γ-Cyclodextrin -Midazolam complex, representing a new chemical formula, was used to improve the solubility and the palatability of the Midazolam formulation. A pharmacokinetic (PK) study has been executed in adults, children and adolescents, whereas ADV6209 showed improvements to current extemporaneous oral solutions of midazolam (EOM) preparations in terms of taste and easiness of use while presenting a similar PK profile. Satisfying sedation, measured with the Observer Assessment of Alertness/Sedation Scale (OAA score / S≤17) was observed in 78.4% of paediatric patients 30 minutes after ADV6209 administration. Anxiety score (modified Yale Preoperative Anxiety Scale - mYPAS) was decreased by 18.3% on average over baseline, 30 minutes after ADV6209 with a more pronounced effect in the youngest children who were also the most anxious prior to administration of the drug. In general the treatment was well accepted by all children and did not induce more crying and nausea / vomiting than before Midazolam. ADV6209 seems a very promising premedication drug. It has been licensed by the EU regulatory authorities to become the first licensed paediatric sedative in the EU (September 2018). It may help to avoid unregistered and off label use of EOM. Consequently, we want to evaluate the efficacy and safety of ADV6209 on preoperative anxiety and sedation levels in paediatric anaesthesia in daily clinical routine in this randomized, controlled, double blinded study.

Study Type

Interventional

Enrollment (Actual)

Phase

Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Austria
- - Vienna, Austria, 1090
    - Medical University of Vienna, Dept. of Anesthesia, Intensive Care Medicine and Pain Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years to 8 years (Child)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Description

Inclusion Criteria:

ASA 1 and 2 children from 2-8 years scheduled for elective surgical or diagnostic procedures, where premedication would be used in clinical routine
Signed written parental informed consent prior to inclusion in the study

Exclusion Criteria:

ASA 3-5
Allergy against the study drug
Participation in another clinical study investigating another IMP within one month prior to screening
Other objections to study participation in the opinion of the investigator
Parent's or legal guardian's refusal of participation of the child

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Interventional Model: Parallel Assignment
Masking: Triple

Number of Arms

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ADV6209 ADV6209 (= gamma-cyclodextrin-Midazolam) 0.25 mg/kg p.o. once 30 min. before anesthesia	Drug: ADV6209 (=gamma-cyclodextrin-Midazolam) 30 min. before anesthesia children have to swallow the anxiolytic drug (ADV6209) Other Names: Ozalin (registered Tradename)
Active Comparator: Midazolam Midazolam (in orange flavored syrup) 0.25 mg/kg p.o. once 30 min. before anesthesia	Drug: Midazolam 30 min. before anesthesia children have to swallow the anxiolytic drug Midazolam Other Names: Dormicum (Tradename)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline of the sedation score (modified Yale Preoperative Anxiety Scale - mYPAS-short form) at 30 minutes after administration of the premedication drug Time Frame: The level of sedation 1 minute before the premedication will be graded and compared to the level of sedation 30 minutes after the oral administration of the drug	The mYPAS-SF consists of four items (activity, vocalizations, emotional expressivity and state of apparent arousal). Each domain consists of Likert-type response options reflecting behaviours. Children's behaviour is rated from 1 to 4 or 1 to 6 (depending on the domain), with higher numbers indicating the highest severity within that domain	The level of sedation 1 minute before the premedication will be graded and compared to the level of sedation 30 minutes after the oral administration of the drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acceptance of oral administration of the premedication drugs Time Frame: Will be evaluated, when the children swallow the premedication drug - 30 minutes before the induction of anaesthesia	Observers record the child's acceptance of the orange-flavoured γ-Cyclodextrin -Midazolam (Ozalin®) (intervention group) or the Midazolam in orange - flavoured syrup (control group) according to the following graduation immediately after administration of the study drug: (1) The child accepts readily, (2) the child accepts with facial grimace, (3) the child accepts with verbal complaint or (4) the child rejects entirely or spits out almost/or all of the dose.	Will be evaluated, when the children swallow the premedication drug - 30 minutes before the induction of anaesthesia
Acceptance of anaesthesia mask induction Time Frame: Will be evaluated, when anaesthesia is induced with the anesthesia mask - 30 minutes after the premedication	Mask Acceptance Score: A four-point mask-induction score will be used to determine the quality of induction of narcosis via face mask as follows: (1) Very good, immediate acceptance of the face mask, (2) good, slight resistance, (3) moderate, struggle against face mask and (4) difficult, moderate force necessary.	Will be evaluated, when anaesthesia is induced with the anesthesia mask - 30 minutes after the premedication

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Medical University of Vienna

Investigators

Principal Investigator: Peter Marhofer, MD, Medical University of Vienna

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 16, 2020

Primary Completion (Actual)

September 17, 2021

Study Completion (Actual)

September 17, 2021

Study Registration Dates

First Submitted

April 23, 2019

First Submitted That Met QC Criteria

April 25, 2019

First Posted (Actual)

April 29, 2019

Study Record Updates

Last Update Posted (Actual)

February 16, 2022

Last Update Submitted That Met QC Criteria

February 15, 2022

Last Verified

February 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

1.4-22.07.2019

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Studies a U.S. FDA-regulated device product

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The Use of ADV6209 for Premedication in Pediatric Anesthesia