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The Use of ADV6209 for Premedication in Pediatric Anesthesia

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ClinicalTrials.gov Identifier: NCT03931057
Recruitment Status : Recruiting
First Posted : April 29, 2019
Last Update Posted : February 20, 2020
Sponsor:
Information provided by (Responsible Party):
Peter Marhofer, Medical University of Vienna

Brief Summary:
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

Condition or disease Intervention/treatment Phase
Preanesthetic Medication Drug: ADV6209 (=gamma-cyclodextrin-Midazolam) Drug: Midazolam Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: A controlled, randomized, double blinded study Study group 1 (40 children) ADV6209 0.25 mg/kg p.o. Study group 2 (40 children) Midazolam (in orange flavoured syrup) 0.25 mg/kg p.o.
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: The Use of ADV6209 for Premedication in Pediatric Anesthesia: a Controlled, Randomized, Double Blinded Study
Estimated Study Start Date : May 2020
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anxiety

Arm Intervention/treatment
Experimental: ADV6209
ADV6209 (= gamma-cyclodextrin-Midazolam) 0.3 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 Name: Ozalin (registered Tradename)

Active Comparator: Midazolam
Midazolam (in orange flavored syrup) 0.3 mg/kg p.o. once 30 min. before anesthesia
Drug: Midazolam
30 min. before anesthesia children have to swallow the anxiolytic drug Midazolam
Other Name: Dormicum (Tradename)




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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.

  2. 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.



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Ages Eligible for Study:   2 Years to 8 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03931057


Contacts
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Contact: Peter Marhofer, MD 0043140400 ext 19227 peter.marhofer@meduniwien.ac.at
Contact: Markus Zadrazil, MD 0043140400 ext 19227 markus.zadrazil@gmail.com

Locations
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Austria
Medical University of Vienna, Dept. of Anesthesia, Intensive Care Medicine and Pain Medicine Recruiting
Vienna, Austria, 1090
Contact: Peter Marhofer, MD    0043140400 ext 19227    peter.marhofer@meduniwien.ac.at   
Contact: Markus Zadrazil, MD    0043140400 ext 19227    markus.zadrazil@meduniwien.ac.at   
Principal Investigator: Peter Marhofer, MD         
Sponsors and Collaborators
Medical University of Vienna
Investigators
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Principal Investigator: Peter Marhofer, MD Medical University of Vienna
Publications:

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Responsible Party: Peter Marhofer, Clinical Professor, MD, Medical University of Vienna
ClinicalTrials.gov Identifier: NCT03931057    
Other Study ID Numbers: 1.4-22.07.2019
First Posted: April 29, 2019    Key Record Dates
Last Update Posted: February 20, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Midazolam
Adjuvants, Anesthesia
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action