Safety and Efficacy of Dexmedetomidine (DEX) for Sedation of Subjects ≥1 Month to <17 Years Undergoing MRI Scans

A PHASE 3/4 RANDOMIZED, DOUBLE-BLIND, DOSE-RANGING STUDY OF THE SAFETY AND EFFICACY OF DEXMEDETOMIDINE (DEX) USED WITH PROPOFOL (PRO) AS NEEDED FOR PROCEDURAL SEDATION OF PEDIATRIC SUBJECTS ≥1 MONTH TO <17 YEARS OF AGE UNDERGOING MRI SCANS

This is a randomized, double-blind, dose-ranging study of the efficacy and safety of dexmedetomidine (DEX) when used with propofol as needed, for procedural sedation of pediatric subjects ≥1 month to <17 years of age undergoing MRI scans in the US and Japan.

Study Overview

• Status: Completed
• Conditions: MRI Sedation
• Intervention / Treatment: Drug: dexmedetomidine; Drug: propofol

• Study Type: Interventional
• Enrollment (Actual): 128
• Phase: Phase 4

Contacts and Locations

Study Locations

• Japan
  • Osaka, Japan, 534-0021
    • Osaka City General Hospital
  • Ibaraki
    • Mito, Ibaraki, Japan, 311-4145
      • Ibaraki Children Hospital
  • Kagawa
    • Zentsuji, Kagawa, Japan, 765-8507
      • Shikoku Medical Center for Children and Adults
  • Osaka
    • Izumi-shi, Osaka, Japan, 594-1101
      • Osaka Women's and Children's Hospital
  • Shizuoka
    • Shizuoka-shi, Shizuoka, Japan, 420 8660
      • Shizuoka Children's Hospital
  • Tokyo
    • Fuchu, Tokyo, Japan, 183-8561
      • Tokyo Metropolitan Children's Medical Center
    • Setagaya-ku, Tokyo, Japan, 157-8535
      • National Center for Child Health and Development
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's
  • California
    • Palo Alto, California, United States, 94304
      • Lucile Packard Children's Hospital, Stanford
    • Sacramento, California, United States, 95817
      • University of California Davis Medical Center
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Baptist Health - Wolfson Children's Hospital
    • West Palm Beach, Florida, United States, 33407
      • St. Mary's Medical Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Children's Healthcare of Atlanta-Egleston
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • IU Health Riley Hospital for Children
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-4245
      • University of Michigan, C.S. Mott Children's Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55454
      • M Health Fairview University of Minnesota Medical Center - West Bank
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Greenville, North Carolina, United States, 27834
      • Vidant Medical Center
    • Greenville, North Carolina, United States, 27834
      • Brody School of Medicine at East Carolina University
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Rainbow Babies and Children's Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • The Children's Hospital at OUMC
  • Texas
    • Dallas, Texas, United States, 75235
      • Children's Medical Center
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 16 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

1. Male or female subject ≥1 month and <17 years of age.
2. American Society of Anesthesiologists (ASA) Physical Status I, II or III.
3. Requires non-intubated, spontaneous breathing, moderate to deep sedation (NI MDS) for a magnetic resonance imaging (MRI) study with an intensivist, anesthesiologist or other proceduralist in attendance.
4. Duration of the MRI scan is expected to take at least 20 minutes but no more than 3 hours to complete

Key Exclusion Criteria:

1. Pregnant female subjects (including those with an indeterminate or positive pregnancy test); breastfeeding female subjects.
2. Weight on Day 1 before randomization is less than the 10th percentile of weight for age and sex in the US and Japan or is greater than the 95th percentile of weight for age and sex in the US or greater than the 97th percentile of weight for age and sex in Japan based on sponsor-provided growth charts.
3. Planned medical procedure during the MRI scan or post-MRI recovery period.
4. Requires endotracheal intubation or laryngeal mask airway (LMA).
5. Known allergy to eggs, egg products, soybeans or soybean products.
6. SpO2 <93 % on room air -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: dexmedetomidine low dose group; low dose of dexmedetomidine to be given	Drug: dexmedetomidine; dexmedetomidine low, middle and high doses are provided as an intravenous bolus loading dose followed by an intravenous maintenance dose infusion throughout the MRI scan; Drug: propofol; propofol IV administration will be given if needed to maintain sedation
EXPERIMENTAL: dexmedetomidine middle dose group; middle dose of dexmedetomidine to be given	Drug: dexmedetomidine; dexmedetomidine low, middle and high doses are provided as an intravenous bolus loading dose followed by an intravenous maintenance dose infusion throughout the MRI scan; Drug: propofol; propofol IV administration will be given if needed to maintain sedation
EXPERIMENTAL: dexmedetomidine high dose group; high dose of dexmedetomidine to be given	Drug: dexmedetomidine; dexmedetomidine low, middle and high doses are provided as an intravenous bolus loading dose followed by an intravenous maintenance dose infusion throughout the MRI scan; Drug: propofol; propofol IV administration will be given if needed to maintain sedation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants at the DEX High Dose Versus Low Dose in the Combined Age Cohorts Who Did Not Require Concomitant PRO to Complete MRI	Percentage of participants who did not require PRO to complete MRI scan in the combined age cohorts are reported in this outcome measure.	Up to maximum of 3 hours during MRI scan on Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants at the DEX High Dose Versus Low Dose in Each Age Cohort Who Did Not Require Concomitant PRO to Complete MRI	Percentage of participants who did not require PRO to complete MRI scan in each age cohort are reported in this outcome measure.	Up to maximum of 3 hours during MRI scan on Day 1
Percentage of Participants at the DEX Middle Dose vs Low Dose and High Dose vs Middle Dose in Each Age Cohort and Combined Age Cohorts Who Did Not Require Concomitant PRO to Complete MRI	Percentage of participants who did not require PRO to complete MRI scan in each age cohort and combined age cohorts are reported in this outcome measure.	Up to maximum of 3 hours during MRI scan on Day 1
Percentage of Time at Target Pediatric Sedation State Scale (PSSS) Score of 2 After the Administration of the DEX Loading Dose and During the DEX Maintenance Infusion - By Age Cohort and Combined Age	In this outcome measure percentage of time for which participant had maintained PSSS score of 2 was reported. PSSS score ranges from 0 to 5, where 0= sedation with abnormal physiologic parameters requiring acute intervention, 1= sedation with normal vital signs, but requiring airway intervention, 2= no movement during procedure, no frown, no verbalization of complaint indicating no pain and anxiety, 3= no movement during procedure but expression of pain and anxiety on face, verbalization of complaint, requiring help positioning, 4= movement during procedure requiring gentle immobilization for positioning, verbalization of some discomfort or stress, but no crying or shouting that expresses stress or objection, 5= movement impeding proceduralist and requiring forceful immobilization, crying or shouting during procedure, but vocalization not required. Higher score indicated less sedation.	Up to maximum of 3 hours during MRI scan on Day 1
Time From the Start of DEX Loading Dose Infusion to the Time of First PRO Bolus Infusion - By Age Cohort and Combined Age	Participants who did not have PRO administered were censored.	Up to maximum of 3 hours during MRI scan on Day 1
Emergence Time - By Age Cohort and Combined Age	Emergence time: time from the end of the MRI scan to when the participant met a Modified Aldrete score >=9. Participants who were withdrawn or discharged without reaching a Modified Aldrete score >=9, were censored, time computed from end of MRI scan to time of the last clinical assessment (vital signs). Zero minute was used as the censored time if no vital signs were taken during the post-MRI recovery period. Modified Aldrete score: validated observational medical scoring system that allowed verbal prompts for the measurement of recovery after anesthesia (post anesthesia) which included items: activity, respiration, circulation, consciousness, and oxygenation. Each item was scored from 0 to 2, higher scores signified better recovery. The scores of each item were summed to obtain a total score of 0 to 10, where higher scores indicated well recovered participant post anesthesia.	Post MRI scan on Day 1 up to 24 hours
Number of Participants Who Received PRO - By Age Cohort and Combined Age		Up to maximum of 3 hours during MRI scan on Day 1
Total Amount (mcg Per kg) of Concomitant PRO Required to Successfully Complete MRI - By Age Cohort and Combined Age		Up to maximum of 3 hours during MRI scan on Day 1
Body Weight/Time Adjusted Total Amount (Per kg Per Minute) of Concomitant PRO Required to Successfully Complete MRI - By Age Cohort and Combined Age		Up to maximum of 3 hours during MRI scan on Day 1

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 18, 2020
• Primary Completion (ACTUAL): November 2, 2021
• Study Completion (ACTUAL): November 30, 2021

Study Registration Dates

• First Submitted: January 17, 2020
• First Submitted That Met QC Criteria: January 17, 2020
• First Posted (ACTUAL): January 23, 2020

Study Record Updates

• Last Update Posted (ACTUAL): November 16, 2022
• Last Update Submitted That Met QC Criteria: October 18, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: MRI; dexmedetomidine; propofol; procedural sedation
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Propofol; Dexmedetomidine
• Other Study ID Numbers: C0801039

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

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