Acceptability of Various Available Midazolam Formulations (Syrup, Rectal Suppository, Oro-dispersible Minitablet) in Clinical Practice

Observational Study to Understand Acceptability of Various Available Midazolam Formulations (Syrup, Rectal Suppository, Oro-dispersible Tablet) in Clinical Practice

This observational study aims to gain knowledge on how the different midazolam formulations (oral syrup, rectal suppository, ODMT) are accepted by 2- to 10-year-old pediatric inpatients and outpatients at the University Children's Hospital Basel (UKBB) in Switzerland. The present study will use non-invasive scoring to assess acceptability of the different midazolam formulations.

Study Overview

• Status: Recruiting
• Conditions: Medication Palatability
• Intervention / Treatment: Other: Data collection on acceptability of midazolam administration by 2- to 10-year-old pediatric patients at UKBB

Detailed Description

At the University Children's Hospital Basel (UKBB) in Switzerland, ~ 2500 children are referred to the Pediatric Anesthesiology Unit per year receiving midazolam sedation before surgery. Further, ~2000 children are admitted to the Pediatric Emergency Unit for procedures requiring midazolam sedation per year. Medication palatability is a key element of treatment adherence and successful therapy outcome. In a previous cross-sectional acceptability study in 2- to 10-year-old pediatric patients at UKBB, it was demonstrated that an inorganic calcium carbonate/calcium phosphate carrier material as the main excipient in an oro- dispersible mini-tablet (ODMT) formulation is safe, palatable, and highly acceptable in children. To date, no data for acceptability in terms of palatability and anxiolysis in daily preoperative practice for midazolam oral syrup, rectal suppository or ODMT formulation is available. As such the goal of this observational study is to better understand acceptability of various midazolam formulations (oral syrup, rectal suppository, ODMT) in clinical practice in 2- to 10-year-old pediatric patients at UKBB. .

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Svetlana Beglinger, Dr. med.; Phone Number: +41 61 7042550; Email: svetlana.beglinger@ukbb.ch

Study Locations

• Switzerland
  • Basel, Switzerland, 4056
    • Recruiting
    • University of Basel Children's Hospital (UKBB)
    • Contact: Svetlana Beglinger, Dr. med.; Phone Number: +41 61 7042550; Email: svetlana.beglinger@ukbb.ch
    • Principal Investigator: Svetlana Beglinger, Dr. med.
    • Principal Investigator: Thomas Erb, Prof. Dr. med.
    • Sub-Investigator: Klervi Golhen, PharmD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

2- to 10-year-old pediatric patients in the Pediatric Anesthesiology Unit and Pediatric Emergency Unit at the UKBB. Pediatric patients undergoing elective surgical or emergency procedures requiring anxiolysis with midazolam during clinical routine will be enrolled in the study.

Description

Inclusion Criteria:

• Children from 2 years (meaning 2 years 0/12 months) to younger than 10 years (meaning 9 years 12/12 months) of age at the time of surgery
• Children scheduled for ambulatory or elective surgery or for procedures requiring anxiolysis at the UKBB
• Children qualifying as American Society of Anesthesiologists (ASA) 1 or ASA 2 patients
• Clinically indicated administration of midazolam oral syrup, rectal suppository or ODMT
• Parent or legal guardian has been informed about the study and has signed the Informed Consent Form

Exclusion Criteria:

• Children qualifying as ASA 3 and above patients
• Children arriving at the emergency ward in a critically ill condition which needs immediate intervention (i.e. American Thoracic Society (ATS) Score 1 and 2) and no tolerance for time delay due to informed consent.
• Difficulty in assessing palatability due to neurological impairments
• Hypersensitivity to midazolam, other benzodiazepines, or any formulation excipients
• Hypersensitivity to cherries (syrup)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group 1 (reference: midazolam oral syrup or rectal suppository formulations); Oral syrup or rectal suppository formulation of midazolam prescribed in the Anesthesiology Unit or Emergency Unit of UKBB as current reference formulations in clinical routine.	Other: Data collection on acceptability of midazolam administration by 2- to 10-year-old pediatric patients at UKBB; On the day of entry to the Anesthesiology Unit for an elective surgery, or before an intervention at the Emergency Unit, all children, irrespective of their participation to the present study, will receive standard midazolam dose of 0.3-0.5 mg/kg as prescribed by the treating clinician at UKBB in line with clinical practice (as oral syrup, rectal suppository or ODMT). The children's spontaneous reactions after intake of midazolam (e.g., positive comments, spitting out of medication, crying) will be observed and recorded by the research staff. Children who are able to understand the Hedonic Scale (FHS) will be questioned on how they liked the medication by pointing to the appropriate face of a Facial Hedonic Scale (FHS) at the time of midazolam intake.
Group 2 (alternative: midazolam oro- dispersible mini-tablet (OMDT) formulation); ODMT formulation of midazolam prescribed in the Anesthesiology or Emergency Unit at UKBB as a recently introduced alternative formulation in clinical routine.	Other: Data collection on acceptability of midazolam administration by 2- to 10-year-old pediatric patients at UKBB; On the day of entry to the Anesthesiology Unit for an elective surgery, or before an intervention at the Emergency Unit, all children, irrespective of their participation to the present study, will receive standard midazolam dose of 0.3-0.5 mg/kg as prescribed by the treating clinician at UKBB in line with clinical practice (as oral syrup, rectal suppository or ODMT). The children's spontaneous reactions after intake of midazolam (e.g., positive comments, spitting out of medication, crying) will be observed and recorded by the research staff. Children who are able to understand the Hedonic Scale (FHS) will be questioned on how they liked the medication by pointing to the appropriate face of a Facial Hedonic Scale (FHS) at the time of midazolam intake.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Children's acceptance after intake of midazolam rated by research staff	4-point acceptability scale (from "child liked the medication" to "child did not like the medication") rated by research staff	one time assessment at baseline
Children's acceptance after intake of midazolam rated by the pediatric patients	Children who are able to understand the Facial Hedonic Scale (FHS) will be questioned on how they liked the medication by pointing to the appropriate face of a Facial Hedonic Scale (FHS) at the time of midazolam intake. Each face will be associated to a number from a scale to 1 (very bad) to 6 (very good). The spontaneous reactions of the patient will be recorded to identify acceptability.	one time assessment at baseline

Collaborators and Investigators

• Sponsor: University Children's Hospital Basel
• Investigators: Principal Investigator: Svetlana Beglinger, Dr. med., University of Basel Children's Hospital (UKBB)

Study record dates

Study Major Dates

• Study Start (Actual): June 6, 2023
• Primary Completion (Estimated): December 1, 2023
• Study Completion (Estimated): December 1, 2023

Study Registration Dates

• First Submitted: May 30, 2023
• First Submitted That Met QC Criteria: May 30, 2023
• First Posted (Actual): June 8, 2023

Study Record Updates

• Last Update Posted (Actual): October 24, 2023
• Last Update Submitted That Met QC Criteria: October 23, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: midazolam; anxiolysis; midazolam oral syrup; midazolam rectal suppository; midazolam oro- dispersible mini-tablet; drug-adherence in pediatrics; pediatric sedation management
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Midazolam
• Other Study ID Numbers: 2023-00302; ks22Pfister2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No