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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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MRI Sedation

Intervention / Treatment
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* Drug: dexmedetomidine
* Drug: propofol


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Male or female subject ≥1 month and <17 years of age. American Society of Anesthesiologists (ASA) Physical Status I, II or III. 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. Duration of the MRI scan is expected to take at least 20 minutes but no more than 3 hours to complete Key Exclusion Criteria: Pregnant female subjects (including those with an indeterminate or positive pregnancy test); breastfeeding female subjects. 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. Planned medical procedure during the MRI scan or post-MRI recovery period. Requires endotracheal intubation or laryngeal mask airway (LMA). Known allergy to eggs, egg products, soybeans or soybean products. SpO2 <93 % on room air -

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: dexmedetomidine low dose group<br>low dose of dexmedetomidine to be given | Drug: dexmedetomidine<br>* 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<br>Drug: propofol<br>* propofol IV administration will be given if needed to maintain sedation<br>|
| Experimental: dexmedetomidine middle dose group<br>middle dose of dexmedetomidine to be given | Drug: dexmedetomidine<br>* 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<br>Drug: propofol<br>* propofol IV administration will be given if needed to maintain sedation<br>|
| Experimental: dexmedetomidine high dose group<br>high dose of dexmedetomidine to be given | Drug: dexmedetomidine<br>* 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<br>Drug: propofol<br>* propofol IV administration will be given if needed to maintain sedation<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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procedural sedation, dexmedetomidine, propofol, MRI