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出境医 / 临床实验 / The Use of ADV6209 for Premedication in Pediatric Anesthesia
The Use of ADV6209 for Premedication in Pediatric Anesthesia
Study Description
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.
Study Design
| 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 |
| Actual Study Start Date : | November 16, 2020 |
| Estimated Primary Completion Date : | October 2021 |
| Estimated Study Completion Date : | October 2021 |
Arms and Interventions
| 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 Name: 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 Name: Dormicum (Tradename)
|
Outcome Measures
Primary Outcome Measures :
- 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 :
- 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.
- 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.
Eligibility Criteria
| 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
Contacts and Locations
Contacts
| Contact: Peter Marhofer, MD | 0043140400 ext 19227 | peter.marhofer@meduniwien.ac.at | |
| Contact: Markus Zadrazil, MD | 0043140400 ext 19227 | markus.zadrazil@gmail.com |
Locations
| 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
| Principal Investigator: | Peter Marhofer, MD | Medical University of Vienna |
| Tracking Information | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| First Submitted Date ICMJE | April 23, 2019 | ||||||||
| First Posted Date ICMJE | April 29, 2019 | ||||||||
| Last Update Posted Date | November 27, 2020 | ||||||||
| Actual Study Start Date ICMJE | November 16, 2020 | ||||||||
| Estimated Primary Completion Date | October 2021 (Final data collection date for primary outcome measure) | ||||||||
| Current Primary Outcome Measures ICMJE |
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
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| Original Primary Outcome Measures ICMJE |
Change from baseline of the sedation score (modified Yale Preoperative Anxiety Scale - mYPAS) 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 consists of five items (activity, vocalizations, emotional expressivity, state of apparent arousal, and use of parent). 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
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| Change History | |||||||||
| Current Secondary Outcome Measures ICMJE |
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| Original Secondary Outcome Measures ICMJE |
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| Current Other Pre-specified Outcome Measures | Not Provided | ||||||||
| Original Other Pre-specified Outcome Measures | Not Provided | ||||||||
| Descriptive Information | |||||||||
| Brief Title ICMJE | The Use of ADV6209 for Premedication in Pediatric Anesthesia | ||||||||
| Official Title ICMJE | The Use of ADV6209 for Premedication in Pediatric Anesthesia: a Controlled, Randomized, Double Blinded Study | ||||||||
| 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 | ||||||||
| 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 ICMJE | Interventional | ||||||||
| Study Phase ICMJE | Phase 4 | ||||||||
| Study Design ICMJE | 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 |
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| Condition ICMJE | Preanesthetic Medication | ||||||||
| Intervention ICMJE |
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| Study Arms ICMJE |
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| Publications * |
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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| Recruitment Information | |||||||||
| Recruitment Status ICMJE | Recruiting | ||||||||
| Estimated Enrollment ICMJE |
80 | ||||||||
| Original Estimated Enrollment ICMJE | Same as current | ||||||||
| Estimated Study Completion Date ICMJE | October 2021 | ||||||||
| Estimated Primary Completion Date | October 2021 (Final data collection date for primary outcome measure) | ||||||||
| Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
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| Sex/Gender ICMJE |
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| Ages ICMJE | 2 Years to 8 Years (Child) | ||||||||
| Accepts Healthy Volunteers ICMJE | No | ||||||||
| Contacts ICMJE |
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| Listed Location Countries ICMJE | Austria | ||||||||
| Removed Location Countries | |||||||||
| Administrative Information | |||||||||
| NCT Number ICMJE | NCT03931057 | ||||||||
| Other Study ID Numbers ICMJE | 1.4-22.07.2019 | ||||||||
| Has Data Monitoring Committee | No | ||||||||
| U.S. FDA-regulated Product |
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| IPD Sharing Statement ICMJE |
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| Responsible Party | Peter Marhofer, Medical University of Vienna | ||||||||
| Study Sponsor ICMJE | Medical University of Vienna | ||||||||
| Collaborators ICMJE | Not Provided | ||||||||
| Investigators ICMJE |
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| PRS Account | Medical University of Vienna | ||||||||
| Verification Date | November 2020 | ||||||||
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ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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