DOSE Trial of Opioid Sparing Effect

• Sponsor: Duke University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03938857
• Collaborator: National Institutes of Health (NIH) (NIH), Johns Hopkins University (Other), Intermountain Health Care, Inc. (Other), Vanderbilt University Medical Center (Other)
• Enrollment: 30
• Locations: 19
• Arms: 4
• Actual Duration (Months): 15.7
• Patients Per Site: 1.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Multicenter, double blind randomized controlled trial of fentanyl vs. fentanyl + dexmedetomidine as the initial regimen for maintenance of sedation in mechanically-ventilated, critically ill children.

This trial will evaluate the opioid-sparing effect of dexmedetomidine when administered with fentanyl to mechanically ventilated, critically ill children. Study drug or placebo will be administered with fentanyl, which will be titrated to achieve sedation scores consistent with response to light touch. Plasma samples and bedside assessments for pain, sedation, and delirium will be collected.

Condition or Disease	Intervention/Treatment	Phase
Dexmedetomidine; Mechanical Ventilation Complication; Critically Ill	Drug: Fentanyl; Drug: Dexmedetomidine; Drug: Dexmedetomidine; Drug: Dexmedetomidine	Phase 1

Detailed Description

Phase 1b randomized, double-blind, placebo-controlled dose escalation trial of sedation regimens in critically ill children. Testing the hypothesis of mean daily fentanyl dose through day 7 of mechanical ventilation will be reduced by ≥25% by the addition of dexmedetomidine to fentanyl therapy. This trial will involve multiple clinical sites. Randomization will occur by individual and investigators will be blinded to study/treatment arm. The statistical analysis will account for center effects, participant characteristics (including post-surgical state), and changes over time to minimize bias. In addition, PIs and study coordinators will undergo training to standardize assessment procedures. The study will randomize participants to receive placebo (fentanyl standard of care) titrated to sedation+saline placebo (bolus+infusion) or one of the following 3 Dexmedetomidine treatment arms in a sequential cohort fashion: Cohort 1: Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2 mcg/kg/hr infusion); Cohort 2: Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion); and, Cohort 3: Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion).

An interim analysis is planned for this trial.

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: Phase 1b randomized, double-blind, placebo-controlled dose escalation trial. The study will randomize participants to receive placebo (fentanyl standard of care) titrated to sedation+saline placebo (bolus+infusion) or one of the following 3 Dexmedetomidine treatment arms in a sequential cohort fashion: Cohort 1: Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2 mcg/kg/hr infusion); Cohort 2: Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion); Cohort 3: Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion).Phase 1b randomized, double-blind, placebo-controlled dose escalation trial. The study will randomize participants to receive placebo (fentanyl standard of care) titrated to sedation+saline placebo (bolus+infusion) or one of the following 3 Dexmedetomidine treatment arms in a sequential cohort fashion: Cohort 1: Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2 mcg/kg/hr infusion); Cohort 2: Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion); Cohort 3: Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion).
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: DEXMEDETOMIDINE OPIOID SPARING EFFECT IN MECHANICALLY VENTILATED CHILDREN: Phase 1b, Multicenter, Double Blind Randomized Controlled Dose Escalating Trial of Fentanyl vs. Fentanyl + Dexmedetomidine as the Initial Regimen for Maintenance of Sedation in Mechanically-ventilated, Critically Ill Children
• Actual Study Start Date: Jul 18, 2019
• Actual Primary Completion Date: Oct 21, 2020
• Actual Study Completion Date: Nov 6, 2020

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Fen. SOC+saline placebo (bolus+infusion) Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion)	Drug: Fentanyl; Fentanyl standard of care
Active Comparator: Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr) Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion)	Drug: Fentanyl; Fentanyl standard of care; Drug: Dexmedetomidine; Dexmedetomidine (0.5 mcg/kg + 0.2 mcg/kg/hr)
Active Comparator: Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr) Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion)	Drug: Fentanyl; Fentanyl standard of care; Drug: Dexmedetomidine; Dexmedetomidine (0.5 mcg/kg + 0.5 mcg/kg/hr)
Active Comparator: Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion)	Drug: Fentanyl; Fentanyl standard of care; Drug: Dexmedetomidine; Dexmedetomidine (0.5 mcg/kg + 0.7 mcg/kg/hr)

Outcome Measures

Primary Outcome Measures

1. Mean Daily Dose of Fentanyl in mcg/kg/hr (Micrograms Per Kilogram Per Hour) [through day 7 of mechanical ventilation or initial extubation (whichever is first)]

   Characterize the opioid-sparing effect of dexmedetomidine when co-administered with fentanyl in children receiving mechanical ventilation. Characterization of differences between dosing exposures for the four groups will allow estimation of the opioid-sparing effect of dexmedetomidine.

Secondary Outcome Measures

1. Sedation Based on the State Behavior Scale (SBS) Relative to Fentanyl Plasma Concentrations (Cmax) [through day 7 of mechanical ventilation or initial extubation (whichever is first)]

   Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The SBS is a 6-point scale that ranges from +2 to -3 with -3. Scores that are more negative reflect a more sedated state (-3). Scores that are more positive reflect a more agitated state (+2). Zero is awake and easily calmed.

2. Sedation Based on SBS Scale Relative to Fentanyl Plasma Concentrations (Cmin) [through day 7 of mechanical ventilation or initial extubation (whichever is first)]

   Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The SBS is a 6-point scale that ranges from +2 to -3 with -3. Scores that are more negative reflect a more sedated state (-3). Scores that are more positive reflect a more agitated state (+2). Zero is awake and easily calmed.

3. Sedation Based on SBS Scale Relative to Fentanyl Plasma Concentrations (Css) [through day 7 of mechanical ventilation or initial extubation (whichever is first)]

   Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The SBS is a 6-point scale that ranges from +2 to -3 with -3. Scores that are more negative reflect a more sedated state (-3). Scores that are more positive reflect a more agitated state (+2). Zero is awake and easily calmed.

4. Sedation Based on SBS Scale Relative to Fentanyl Plasma Concentrations (AUC) [through day 7 of mechanical ventilation or initial extubation (whichever is first)]

   Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The SBS is a 6-point scale that ranges from +2 to -3 with -3. Scores that are more negative reflect a more sedated state (-3). Scores that are more positive reflect a more agitated state (+2). Zero is awake and easily calmed.

5. Sedation Based on SBS Scale Relative to Dexmedetomidine Plasma Concentrations (Cmax) [through day 7 of mechanical ventilation or initial extubation (whichever is first)]

   Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The SBS is a 6-point scale that ranges from +2 to -3 with -3. Scores that are more negative reflect a more sedated state (-3). Scores that are more positive reflect a more agitated state (+2). Zero is awake and easily calmed.

6. Sedation Based on SBS Scale Relative to Dexmedetomidine Plasma Concentrations (Cmin) [through day 7 of mechanical ventilation or initial extubation (whichever is first)]

   Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The SBS is a 6-point scale that ranges from +2 to -3 with -3. Scores that are more negative reflect a more sedated state (-3). Scores that are more positive reflect a more agitated state (+2). Zero is awake and easily calmed.

7. Sedation Based on SBS Scale Relative to Dexmedetomidine Plasma Concentrations (Css) [through day 7 of mechanical ventilation or initial extubation (whichever is first)]

   Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The SBS is a 6-point scale that ranges from +2 to -3 with -3. Scores that are more negative reflect a more sedated state (-3). Scores that are more positive reflect a more agitated state (+2). Zero is awake and easily calmed.

8. Sedation Based on SBS Scale Relative to Dexmedetomidine Plasma Concentrations (AUC) [through day 7 of mechanical ventilation or initial extubation (whichever is first)]

   Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The SBS is a 6-point scale that ranges from +2 to -3 with -3. Scores that are more negative reflect a more sedated state (-3). Scores that are more positive reflect a more agitated state (+2). Zero is awake and easily calmed.

9. Sedation Based on Richmond Agitation and Sedation Scale (RASS) Scale Relative to Fentanyl Plasma Concentrations (Cmax) [through day 7 of mechanical ventilation or initial extubation (whichever is first)]

   Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The RASS is a 10-point scale that ranges from -5 to +4 with -5=unarousable and +4=combative. Zero means the patient is alert and calm.

10. Sedation Based on RASS Scale Relative to Fentanyl Plasma Concentrations (Cmin) [through day 7 of mechanical ventilation or initial extubation (whichever is first)]

    Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The RASS scale is a 10-pint scale that ranges from -5 to +4 with -5=unarousable and +4=combative. Zero means the patient is alert and calm.

11. Sedation Based on RASS Scale Relative to Fentanyl Plasma Concentrations (Css) [through day 7 of mechanical ventilation or initial extubation (whichever is first)]

    Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The RASS scale is a 10-point scale that ranges from -5 to +4 with -5=unarousable and +4=combative. Zero means the patient is alert and calm.

12. Sedation Based on RASS Scale Relative to Fentanyl Plasma Concentrations (AUC) [through day 7 of mechanical ventilation or initial extubation (whichever is first)]

    Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The RASS scale is a 10-point scale that ranges from -5 to +4 with -5=unarousable and +4=combative. Zero means the patient is alert and calm.

13. Sedation Based on RASS Scale Relative to Dexmedetomidine Plasma Concentrations (Cmax) [through day 7 of mechanical ventilation or initial extubation (whichever is first)]

    Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The RASS scale is a 10-point scale that ranges from -5 to +4 with -5=unarousable and +4=combative. Zero means the patient is alert and calm.

14. Sedation Based on RASS Scale Relative to Dexmedetomidine Plasma Concentrations (Cmin) [through day 7 of mechanical ventilation or initial extubation (whichever is first)]

    Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The RASS scale is a 10-point scale that ranges from -5 to +4 with -5=unarousable and +4=combative. Zero means the patient is alert and calm.

15. Sedation Based on RASS Scale Relative to Dexmedetomidine Plasma Concentrations (Css) [through day 7 of mechanical ventilation or initial extubation (whichever is first)]

    Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The RASS scale is a 10-point scale that ranges from -5 to +4 with -5=unarousable and +4=combative. Zero means the patient is alert and calm.

16. Sedation Based on RASS Scale Relative to Dexmedetomidine Plasma Concentrations (AUC) [through day 7 of mechanical ventilation or initial extubation (whichever is first)]

    Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The RASS scale is a 10-point scale that ranges from -5 to +4 with -5=unarousable and +4=combative. Zero means the patient is alert and calm.

17. Number of Participants Experiencing a Clinically Significant Episode of Hypotension [up to 28 days or until discharge from the ICU (whichever is first)]

    Characterize the safety profile of fentanyl and dexmedetomidine when administered alone or in combination to children receiving mechanical ventilation.

18. Number of Participants Experiencing SAEs (Serious Adverse Events) [up to 28 days or until discharge from the ICU (whichever is first)]

19. Mean Number of SAEs (Serious Adverse Events) Experienced by Participants [up to 28 days or until discharge from the ICU (whichever is first)]

20. Number of Participants Experiencing a Clinically Significant Episode of Bradycardia [up to 28 days or until discharge from the ICU (whichever is first)]

    Characterize the safety profile of fentanyl and dexmedetomidine when administered alone or in combination to children receiving mechanical ventilation.

21. Number of Participants Experiencing a Clinically Significant Episode of Urinary Retention [up to 28 days or until discharge from the ICU (whichever is first)]

    Characterize the safety profile of fentanyl and dexmedetomidine when administered alone or in combination to children receiving mechanical ventilation.

Other Outcome Measures

1. Average Daily Cornell Assessment of Pediatrics in Delirium (CAPD) Scores [through day 7 of mechanical ventilation or initial extubation (whichever is first)]

   Estimate the incidence of intensive care unit delirium in children exposed to fentanyl and dexmedetomidine alone or in combination when receiving mechanical ventilation. (Measures of delirium). The CAPD scale goes from 0-4 and has 8 questions. All items scored as occurring never, rarely, sometimes, often, or always. Individual item scores are added for a sum total score.

2. Maximum Daily CAPD Scores [through day 7 of mechanical ventilation or initial extubation (whichever is first)]

   Estimate the incidence of intensive care unit delirium in children exposed to fentanyl and dexmedetomidine alone or in combination when receiving mechanical ventilation. (Measures of delirium). The CAPD scale goes from 0-4 and has 8 questions. All items scored as occurring never, rarely, sometimes, often, or always. Individual item scores are added for a sum total score.

3. Minimum Daily CAPD Scores [through day 7 of mechanical ventilation or initial extubation (whichever is first)]

   Estimate the incidence of intensive care unit delirium in children exposed to fentanyl and dexmedetomidine alone or in combination when receiving mechanical ventilation. (Measures of delirium). The CAPD scale goes from 0-4 and has 8 questions. All items scored as occurring never, rarely, sometimes, often, or always. Individual item scores are added for a sum total score.

4. Average Daily Withdrawal Assessment Tool (WAT-1) Score [through day 7 of mechanical ventilation or initial extubation (whichever is first)]

   Estimate the incidence of opioid withdrawal syndrome in children exposed to fentanyl and dexmedetomidine when administered alone or in combination when receiving mechanical ventilation. (Measures of withdrawal). WAT-1 scale is 0=no/none and 1=yes/moderate/severe. Total score is on a 0-12 scale where lower is better.

5. Minimum Daily WAT-1 Score [through day 7 of mechanical ventilation or initial extubation (whichever is first)]

   Estimate the incidence of opioid withdrawal syndrome in children exposed to fentanyl and dexmedetomidine when administered alone or in combination when receiving mechanical ventilation. (Measures of withdrawal). WAT-1 scale is 0=no/none and 1=yes/moderate/severe. Total score is on a 0-12 scale where lower is better.

6. Maximum Daily WAT-1 Score [through day 7 of mechanical ventilation or initial extubation (whichever is first)]

   Estimate the incidence of opioid withdrawal syndrome in children exposed to fentanyl and dexmedetomidine when administered alone or in combination when receiving mechanical ventilation. (Measures of withdrawal). WAT-1 scale is 0=no/none and 1=yes/moderate/severe. Total score is on a 0-12 scale where lower is better.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 18 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Ages 0 to <18 years at the time of enrollment.

2. If < 6 months postnatal age, gestational age ≥ 35 weeks.

3. Admitted to an intensive care unit.

4. Planned or anticipated mechanically ventilation for ≥2 days.

5. Require sedation to maintain mechanical ventilation per clinical judgment.

6. No contraindication to receipt of fentanyl or dexmedetomidine per clinician judgment.

7. Availability and willingness of the parent/legal guardian to provide written informed consent.

Exclusion Criteria:

1. Previous participation in this study.

2. Severe traumatic brain injury as the underlying etiology for critical illness requiring mechanical ventilation or baseline pediatric cerebral performance category (PCPC) >3.

3. Planned receipt of sedatives other than fentanyl or dexmedetomidine.

4. Anticipated receipt of neuromuscular blockade for >48 consecutive hours during the study period.

5. Receipt of fentanyl or dexmedetomidine via continuous infusion for >12 hours in the 24 hours prior to enrollment.

6. Extracorporeal life support (including renal replacement therapy, extracorporeal membrane oxygenation, ventricular assist device, etc.) at the time of enrollment.

7. Chronic use of or recent overdose of serotonergic agents (selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase (MAO) inhibitors, cyclic antidepressants)

8. Known pregnancy

9. Known liver dysfunction, defined as: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2x the upper limit of normal for age

10. Known or impending renal failure defined as: anuria > or equal to 12 hours prior to enrollment or requiring renal replacement therapy

11. High risk children, define as: a. known heart block b. known bradyarrythmia including clinically significant bradycardia (defined as requiring chronotropic agents or cardiac pacing to treat)

12. Receipt of mechanical ventilation during an admission for cardiac surgery

Note: receipt of drugs other than fentanyl or dexmedetomidine for intubation, and receipt of neuromuscular blockage for intubation, will not be considered exclusionary criteria.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arkansas Children's Hospital	Little Rock	Arkansas	United States	72202
2	University of Florida, Shands Children's Hospital	Gainesville	Florida	United States	32608
3	Indiana University Health, Riley Hospital for Children	Indianapolis	Indiana	United States	46202
4	Our Lady of the Lake Children's Hospital	Baton Rouge	Louisiana	United States	70808
5	UMass Memorial Medical Center, Children's Center	Worcester	Massachusetts	United States	01655
6	University of Minnesota Masonic Children's Hospital	Minneapolis	Minnesota	United States	55454
7	Saint Louis University, Cardinal Glennon Children's Hospital	Saint Louis	Missouri	United States	63104
8	University of New Mexico Children's Hospital	Albuquerque	New Mexico	United States	87131
9	University of Buffalo, Oishei Children's Hospital	Buffalo	New York	United States	14203
10	University of Rochester Medical Center, Golisano Children's Hospital	Rochester	New York	United States	14642
11	Duke University Medical Center	Durham	North Carolina	United States	27705
12	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina	United States	27157
13	Rainbow Babies and Children's Hospital, University Hospitals Cleveland Medical Center	Cleveland	Ohio	United States	44106
14	MetroHealth System, Case CTSA	Cleveland	Ohio	United States	44109
15	Oregon Health and Science University, Doernbecher Children's Hospital	Portland	Oregon	United States	97239
16	Drexel University, St. Christopher's Hospital for Children	Philadelphia	Pennsylvania	United States	19134
17	Medical University of South Carolina Children's Hospital	Charleston	South Carolina	United States	29425
18	University of Texas - Health Science Center San Antonio	San Antonio	Texas	United States	78229
19	Primary Children's Medical Center- University of Utah	Salt Lake City	Utah	United States	84113

Sponsors and Collaborators

• Duke University
• National Institutes of Health (NIH)
• Johns Hopkins University
• Intermountain Health Care, Inc.
• Vanderbilt University Medical Center

Investigators

• Principal Investigator: Daniel Benjamin, MD, Duke Clinical Research Institute

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 10, 2020
• Informed Consent Form - Apr 16, 2020

More Information

Publications

None provided.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT03938857
• Other Study ID Numbers: Pro00102267; 5U24TR001608
• First Posted: May 6, 2019
• Last Update Posted: Nov 5, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Critical Illness; Fentanyl; Dexmedetomidine

Study Results

Participant Flow

Recruitment Details	Subjects enrolled were in a pediatric intensive care setting, critically ill and requiring ventilatory support and pain management associated with such.

Arm/Group Title	Fen. SOC+Saline Placebo (Bolus+Infusion)	Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr)
Arm/Group Description	Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion) Fentanyl: Fentanyl standard of care	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.2 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.5 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.7 mcg/kg/hr)
Period Title: Overall Study
STARTED	6	12	12	0
COMPLETED	5	12	12	0
NOT COMPLETED	1	0	0	0

Baseline Characteristics

Arm/Group Title	Fen. SOC+Saline Placebo (Bolus+Infusion)	Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr)	Total
Arm/Group Description	Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion) Fentanyl: Fentanyl standard of care	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.2 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.5 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.7 mcg/kg/hr)	Total of all reporting groups
Overall Participants	6	12	12	0	30
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	3.8 (6.8)	2.5 (2.8)	2.6 (3.7)	2.8 (4.0)
Sex: Female, Male (Count of Participants)
Female	3 50%	5 41.7%	4 33.3%	12 Infinity
Male	3 50%	7 58.3%	8 66.7%	18 Infinity
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 8.3%	1 8.3%	2 Infinity
Not Hispanic or Latino	5 83.3%	11 91.7%	10 83.3%	26 Infinity
Unknown or Not Reported	1 16.7%	0 0%	1 8.3%	2 Infinity
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 NaN
Asian	0 0%	0 0%	0 0%	0 NaN
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 NaN
Black or African American	3 50%	3 25%	1 8.3%	7 Infinity
White	3 50%	8 66.7%	8 66.7%	19 Infinity
More than one race	0 0%	0 0%	1 8.3%	1 Infinity
Unknown or Not Reported	0 0%	1 8.3%	2 16.7%	3 Infinity
Region of Enrollment (Count of Participants)
United States	6 100%	12 100%	12 100%	30 Infinity

Outcome Measures

1. Primary Outcome

Title	Mean Daily Dose of Fentanyl in mcg/kg/hr (Micrograms Per Kilogram Per Hour)
Description	Characterize the opioid-sparing effect of dexmedetomidine when co-administered with fentanyl in children receiving mechanical ventilation. Characterization of differences between dosing exposures for the four groups will allow estimation of the opioid-sparing effect of dexmedetomidine.
Time Frame	through day 7 of mechanical ventilation or initial extubation (whichever is first)

Outcome Measure Data

Analysis Population Description

Patients who did not have fentanyl reported were excluded. No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.

Arm/Group Title	Fen. SOC+Saline Placebo (Bolus+Infusion)	Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr)
Arm/Group Description	Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion) Fentanyl: Fentanyl standard of care	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.2 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.5 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.7 mcg/kg/hr)
Measure Participants	6	12	12	0
Mean (Standard Deviation) [mcg/kg/hr]	2.25 (2.15)	2.68 (1.53)	3.23 (3.30)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fen. SOC+Saline Placebo (Bolus+Infusion), Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr), Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr)
	Comments	Placebo group compared to combined Dexmedetomidine groups.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.814
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	-0.1088295
	Confidence Interval	(2-Sided) 95%; -1.035508 to 0.8178494
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.4728041
	Estimation Comments	Estimated value represents interaction between treatment and days.

2. Secondary Outcome

Title	Sedation Based on the State Behavior Scale (SBS) Relative to Fentanyl Plasma Concentrations (Cmax)
Description	Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The SBS is a 6-point scale that ranges from +2 to -3 with -3. Scores that are more negative reflect a more sedated state (-3). Scores that are more positive reflect a more agitated state (+2). Zero is awake and easily calmed.
Time Frame	through day 7 of mechanical ventilation or initial extubation (whichever is first)

Outcome Measure Data

Analysis Population Description

Data not collected. The study was terminated early due to enrollment challenges.

Arm/Group Title	Fen. SOC+Saline Placebo (Bolus+Infusion)	Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr)
Arm/Group Description	Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion) Fentanyl: Fentanyl standard of care	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.2 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.5 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.7 mcg/kg/hr)
Measure Participants	0	0	0	0

3. Secondary Outcome

Title	Sedation Based on SBS Scale Relative to Fentanyl Plasma Concentrations (Cmin)
Description	Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The SBS is a 6-point scale that ranges from +2 to -3 with -3. Scores that are more negative reflect a more sedated state (-3). Scores that are more positive reflect a more agitated state (+2). Zero is awake and easily calmed.
Time Frame	through day 7 of mechanical ventilation or initial extubation (whichever is first)

Outcome Measure Data

Analysis Population Description

Data not collected. The study was terminated early due to enrollment challenges.

Arm/Group Title	Fen. SOC+Saline Placebo (Bolus+Infusion)	Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr)
Arm/Group Description	Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion) Fentanyl: Fentanyl standard of care	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.2 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.5 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.7 mcg/kg/hr)
Measure Participants	0	0	0	0

4. Secondary Outcome

Title	Sedation Based on SBS Scale Relative to Fentanyl Plasma Concentrations (Css)
Description	Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The SBS is a 6-point scale that ranges from +2 to -3 with -3. Scores that are more negative reflect a more sedated state (-3). Scores that are more positive reflect a more agitated state (+2). Zero is awake and easily calmed.
Time Frame	through day 7 of mechanical ventilation or initial extubation (whichever is first)

Outcome Measure Data

Analysis Population Description

Data not collected. The study was terminated early due to enrollment challenges.

Arm/Group Title	Fen. SOC+Saline Placebo (Bolus+Infusion)	Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr)
Arm/Group Description	Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion) Fentanyl: Fentanyl standard of care	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.2 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.5 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.7 mcg/kg/hr)
Measure Participants	0	0	0	0

5. Secondary Outcome

Title	Sedation Based on SBS Scale Relative to Fentanyl Plasma Concentrations (AUC)
Description	Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The SBS is a 6-point scale that ranges from +2 to -3 with -3. Scores that are more negative reflect a more sedated state (-3). Scores that are more positive reflect a more agitated state (+2). Zero is awake and easily calmed.
Time Frame	through day 7 of mechanical ventilation or initial extubation (whichever is first)

Outcome Measure Data

Analysis Population Description

Data not collected. The study was terminated early due to enrollment challenges.

Arm/Group Title	Fen. SOC+Saline Placebo (Bolus+Infusion)	Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr)
Arm/Group Description	Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion) Fentanyl: Fentanyl standard of care	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.2 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.5 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.7 mcg/kg/hr)
Measure Participants	0	0	0	0

6. Secondary Outcome

Title	Sedation Based on SBS Scale Relative to Dexmedetomidine Plasma Concentrations (Cmax)
Description	Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The SBS is a 6-point scale that ranges from +2 to -3 with -3. Scores that are more negative reflect a more sedated state (-3). Scores that are more positive reflect a more agitated state (+2). Zero is awake and easily calmed.
Time Frame	through day 7 of mechanical ventilation or initial extubation (whichever is first)

Outcome Measure Data

Analysis Population Description

Data not collected. The study was terminated early due to enrollment challenges.

Arm/Group Title	Fen. SOC+Saline Placebo (Bolus+Infusion)	Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr)
Arm/Group Description	Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion) Fentanyl: Fentanyl standard of care	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.2 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.5 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.7 mcg/kg/hr)
Measure Participants	0	0	0	0

7. Secondary Outcome

Title	Sedation Based on SBS Scale Relative to Dexmedetomidine Plasma Concentrations (Cmin)
Description	Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The SBS is a 6-point scale that ranges from +2 to -3 with -3. Scores that are more negative reflect a more sedated state (-3). Scores that are more positive reflect a more agitated state (+2). Zero is awake and easily calmed.
Time Frame	through day 7 of mechanical ventilation or initial extubation (whichever is first)

Outcome Measure Data

Analysis Population Description

Data not collected. The study was terminated early due to enrollment challenges.

Arm/Group Title	Fen. SOC+Saline Placebo (Bolus+Infusion)	Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr)
Arm/Group Description	Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion) Fentanyl: Fentanyl standard of care	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.2 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.5 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.7 mcg/kg/hr)
Measure Participants	0	0	0	0

8. Secondary Outcome

Title	Sedation Based on SBS Scale Relative to Dexmedetomidine Plasma Concentrations (Css)
Description	Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The SBS is a 6-point scale that ranges from +2 to -3 with -3. Scores that are more negative reflect a more sedated state (-3). Scores that are more positive reflect a more agitated state (+2). Zero is awake and easily calmed.
Time Frame	through day 7 of mechanical ventilation or initial extubation (whichever is first)

Outcome Measure Data

Analysis Population Description

Data not collected. The study was terminated early due to enrollment challenges.

Arm/Group Title	Fen. SOC+Saline Placebo (Bolus+Infusion)	Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr)
Arm/Group Description	Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion) Fentanyl: Fentanyl standard of care	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.2 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.5 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.7 mcg/kg/hr)
Measure Participants	0	0	0	0

9. Secondary Outcome

Title	Sedation Based on SBS Scale Relative to Dexmedetomidine Plasma Concentrations (AUC)
Description	Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The SBS is a 6-point scale that ranges from +2 to -3 with -3. Scores that are more negative reflect a more sedated state (-3). Scores that are more positive reflect a more agitated state (+2). Zero is awake and easily calmed.
Time Frame	through day 7 of mechanical ventilation or initial extubation (whichever is first)

Outcome Measure Data

Analysis Population Description

Data not collected. The study was terminated early due to enrollment challenges.

Arm/Group Title	Fen. SOC+Saline Placebo (Bolus+Infusion)	Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr)
Arm/Group Description	Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion) Fentanyl: Fentanyl standard of care	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.2 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.5 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.7 mcg/kg/hr)
Measure Participants	0	0	0	0

10. Secondary Outcome

Title	Sedation Based on Richmond Agitation and Sedation Scale (RASS) Scale Relative to Fentanyl Plasma Concentrations (Cmax)
Description	Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The RASS is a 10-point scale that ranges from -5 to +4 with -5=unarousable and +4=combative. Zero means the patient is alert and calm.
Time Frame	through day 7 of mechanical ventilation or initial extubation (whichever is first)

Outcome Measure Data

Analysis Population Description

Data not collected. The study was terminated early due to enrollment challenges.

Arm/Group Title	Fen. SOC+Saline Placebo (Bolus+Infusion)	Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr)
Arm/Group Description	Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion) Fentanyl: Fentanyl standard of care	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.2 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.5 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.7 mcg/kg/hr)
Measure Participants	0	0	0	0

11. Secondary Outcome

Title	Sedation Based on RASS Scale Relative to Fentanyl Plasma Concentrations (Cmin)
Description	Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The RASS scale is a 10-pint scale that ranges from -5 to +4 with -5=unarousable and +4=combative. Zero means the patient is alert and calm.
Time Frame	through day 7 of mechanical ventilation or initial extubation (whichever is first)

Outcome Measure Data

Analysis Population Description

Data not collected. The study was terminated early due to enrollment challenges.

Arm/Group Title	Fen. SOC+Saline Placebo (Bolus+Infusion)	Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr)
Arm/Group Description	Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion) Fentanyl: Fentanyl standard of care	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.2 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.5 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.7 mcg/kg/hr)
Measure Participants	0	0	0	0

12. Secondary Outcome

Title	Sedation Based on RASS Scale Relative to Fentanyl Plasma Concentrations (Css)
Description	Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The RASS scale is a 10-point scale that ranges from -5 to +4 with -5=unarousable and +4=combative. Zero means the patient is alert and calm.
Time Frame	through day 7 of mechanical ventilation or initial extubation (whichever is first)

Outcome Measure Data

Analysis Population Description

Data not collected. The study was terminated early due to enrollment challenges.

Arm/Group Title	Fen. SOC+Saline Placebo (Bolus+Infusion)	Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr)
Arm/Group Description	Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion) Fentanyl: Fentanyl standard of care	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.2 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.5 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.7 mcg/kg/hr)
Measure Participants	0	0	0	0

13. Secondary Outcome

Title	Sedation Based on RASS Scale Relative to Fentanyl Plasma Concentrations (AUC)
Description	Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The RASS scale is a 10-point scale that ranges from -5 to +4 with -5=unarousable and +4=combative. Zero means the patient is alert and calm.
Time Frame	through day 7 of mechanical ventilation or initial extubation (whichever is first)

Outcome Measure Data

Analysis Population Description

Data not collected. The study was terminated early due to enrollment challenges.

Arm/Group Title	Fen. SOC+Saline Placebo (Bolus+Infusion)	Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr)
Arm/Group Description	Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion) Fentanyl: Fentanyl standard of care	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.2 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.5 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.7 mcg/kg/hr)
Measure Participants	0	0	0	0

14. Secondary Outcome

Title	Sedation Based on RASS Scale Relative to Dexmedetomidine Plasma Concentrations (Cmax)
Description	Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The RASS scale is a 10-point scale that ranges from -5 to +4 with -5=unarousable and +4=combative. Zero means the patient is alert and calm.
Time Frame	through day 7 of mechanical ventilation or initial extubation (whichever is first)

Outcome Measure Data

Analysis Population Description

Data not collected. The study was terminated early due to enrollment challenges.

Arm/Group Title	Fen. SOC+Saline Placebo (Bolus+Infusion)	Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr)
Arm/Group Description	Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion) Fentanyl: Fentanyl standard of care	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.2 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.5 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.7 mcg/kg/hr)
Measure Participants	0	0	0	0

15. Secondary Outcome

Title	Sedation Based on RASS Scale Relative to Dexmedetomidine Plasma Concentrations (Cmin)
Description	Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The RASS scale is a 10-point scale that ranges from -5 to +4 with -5=unarousable and +4=combative. Zero means the patient is alert and calm.
Time Frame	through day 7 of mechanical ventilation or initial extubation (whichever is first)

Outcome Measure Data

Analysis Population Description

Data not collected. The study was terminated early due to enrollment challenges.

Arm/Group Title	Fen. SOC+Saline Placebo (Bolus+Infusion)	Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr)
Arm/Group Description	Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion) Fentanyl: Fentanyl standard of care	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.2 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.5 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.7 mcg/kg/hr)
Measure Participants	0	0	0	0

16. Secondary Outcome

Title	Sedation Based on RASS Scale Relative to Dexmedetomidine Plasma Concentrations (Css)
Description	Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The RASS scale is a 10-point scale that ranges from -5 to +4 with -5=unarousable and +4=combative. Zero means the patient is alert and calm.
Time Frame	through day 7 of mechanical ventilation or initial extubation (whichever is first)

Outcome Measure Data

Analysis Population Description

Data not collected. The study was terminated early due to enrollment challenges.

Arm/Group Title	Fen. SOC+Saline Placebo (Bolus+Infusion)	Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr)
Arm/Group Description	Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion) Fentanyl: Fentanyl standard of care	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.2 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.5 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.7 mcg/kg/hr)
Measure Participants	0	0	0	0

17. Secondary Outcome

Title	Sedation Based on RASS Scale Relative to Dexmedetomidine Plasma Concentrations (AUC)
Description	Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The RASS scale is a 10-point scale that ranges from -5 to +4 with -5=unarousable and +4=combative. Zero means the patient is alert and calm.
Time Frame	through day 7 of mechanical ventilation or initial extubation (whichever is first)

Outcome Measure Data

Analysis Population Description

Data not collected. The study was terminated early due to enrollment challenges.

Arm/Group Title	Fen. SOC+Saline Placebo (Bolus+Infusion)	Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr)
Arm/Group Description	Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion) Fentanyl: Fentanyl standard of care	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.2 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.5 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.7 mcg/kg/hr)
Measure Participants	0	0	0	0

18. Secondary Outcome

Title	Number of Participants Experiencing a Clinically Significant Episode of Hypotension
Description	Characterize the safety profile of fentanyl and dexmedetomidine when administered alone or in combination to children receiving mechanical ventilation.
Time Frame	up to 28 days or until discharge from the ICU (whichever is first)

Outcome Measure Data

Analysis Population Description

Participants with data collected. No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.

Arm/Group Title	Fen. SOC+Saline Placebo (Bolus+Infusion)	Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr)
Arm/Group Description	Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion) Fentanyl: Fentanyl standard of care	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.2 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.5 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.7 mcg/kg/hr)
Measure Participants	5	12	12	0
Count of Participants [Participants]	2 33.3%	5 41.7%	3 25%

19. Secondary Outcome

Title	Number of Participants Experiencing SAEs (Serious Adverse Events)
Time Frame	up to 28 days or until discharge from the ICU (whichever is first)

Outcome Measure Data

Analysis Population Description

No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.

Arm/Group Title	Fen. SOC+Saline Placebo (Bolus+Infusion)	Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr)
Arm/Group Description	Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion) Fentanyl: Fentanyl standard of care	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.2 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.5 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.7 mcg/kg/hr)
Measure Participants	6	12	12	0
Count of Participants [Participants]	0 0%	2 16.7%	1 8.3%

20. Secondary Outcome

Title	Mean Number of SAEs (Serious Adverse Events) Experienced by Participants
Time Frame	up to 28 days or until discharge from the ICU (whichever is first)

Outcome Measure Data

Analysis Population Description

Participants who experienced at least one SAE. No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.

Arm/Group Title	Fen. SOC+Saline Placebo (Bolus+Infusion)	Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr)
Arm/Group Description	Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion) Fentanyl: Fentanyl standard of care	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.2 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.5 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.7 mcg/kg/hr)
Measure Participants	0	2	1	0
Mean (Standard Deviation) [serious adverse events]	1 (0)	1 (NA)

21. Secondary Outcome

Title	Number of Participants Experiencing a Clinically Significant Episode of Bradycardia
Description	Characterize the safety profile of fentanyl and dexmedetomidine when administered alone or in combination to children receiving mechanical ventilation.
Time Frame	up to 28 days or until discharge from the ICU (whichever is first)

Outcome Measure Data

Analysis Population Description

Participants with data collected. No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.

Arm/Group Title	Fen. SOC+Saline Placebo (Bolus+Infusion)	Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr)
Arm/Group Description	Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion) Fentanyl: Fentanyl standard of care	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.2 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.5 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.7 mcg/kg/hr)
Measure Participants	5	12	12	0
Count of Participants [Participants]	2 33.3%	3 25%	1 8.3%

22. Secondary Outcome

Title	Number of Participants Experiencing a Clinically Significant Episode of Urinary Retention
Description	Characterize the safety profile of fentanyl and dexmedetomidine when administered alone or in combination to children receiving mechanical ventilation.
Time Frame	up to 28 days or until discharge from the ICU (whichever is first)

Outcome Measure Data

Analysis Population Description

Participants with data collected. No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.

Arm/Group Title	Fen. SOC+Saline Placebo (Bolus+Infusion)	Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr)
Arm/Group Description	Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion) Fentanyl: Fentanyl standard of care	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.2 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.5 mcg/kg/hr)	Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.7 mcg/kg/hr)
Measure Participants	5	11	11	0
Count of Participants [Participants]	1 16.7%	2 16.7%	1 8.3%

23. Other Pre-specified Outcome

Title	Average Daily Cornell Assessment of Pediatrics in Delirium (CAPD) Scores
Description	Estimate the incidence of intensive care unit delirium in children exposed to fentanyl and dexmedetomidine alone or in combination when receiving mechanical ventilation. (Measures of delirium). The CAPD scale goes from 0-4 and has 8 questions. All items scored as occurring never, rarely, sometimes, often, or always. Individual item scores are added for a sum total score.
Time Frame	through day 7 of mechanical ventilation or initial extubation (whichever is first)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

24. Other Pre-specified Outcome

Title	Maximum Daily CAPD Scores
Description	Estimate the incidence of intensive care unit delirium in children exposed to fentanyl and dexmedetomidine alone or in combination when receiving mechanical ventilation. (Measures of delirium). The CAPD scale goes from 0-4 and has 8 questions. All items scored as occurring never, rarely, sometimes, often, or always. Individual item scores are added for a sum total score.
Time Frame	through day 7 of mechanical ventilation or initial extubation (whichever is first)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

25. Other Pre-specified Outcome

Title	Minimum Daily CAPD Scores
Description	Estimate the incidence of intensive care unit delirium in children exposed to fentanyl and dexmedetomidine alone or in combination when receiving mechanical ventilation. (Measures of delirium). The CAPD scale goes from 0-4 and has 8 questions. All items scored as occurring never, rarely, sometimes, often, or always. Individual item scores are added for a sum total score.
Time Frame	through day 7 of mechanical ventilation or initial extubation (whichever is first)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

26. Other Pre-specified Outcome

Title	Average Daily Withdrawal Assessment Tool (WAT-1) Score
Description	Estimate the incidence of opioid withdrawal syndrome in children exposed to fentanyl and dexmedetomidine when administered alone or in combination when receiving mechanical ventilation. (Measures of withdrawal). WAT-1 scale is 0=no/none and 1=yes/moderate/severe. Total score is on a 0-12 scale where lower is better.
Time Frame	through day 7 of mechanical ventilation or initial extubation (whichever is first)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

27. Other Pre-specified Outcome

Title	Minimum Daily WAT-1 Score
Description	Estimate the incidence of opioid withdrawal syndrome in children exposed to fentanyl and dexmedetomidine when administered alone or in combination when receiving mechanical ventilation. (Measures of withdrawal). WAT-1 scale is 0=no/none and 1=yes/moderate/severe. Total score is on a 0-12 scale where lower is better.
Time Frame	through day 7 of mechanical ventilation or initial extubation (whichever is first)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

28. Other Pre-specified Outcome

Title	Maximum Daily WAT-1 Score
Description	Estimate the incidence of opioid withdrawal syndrome in children exposed to fentanyl and dexmedetomidine when administered alone or in combination when receiving mechanical ventilation. (Measures of withdrawal). WAT-1 scale is 0=no/none and 1=yes/moderate/severe. Total score is on a 0-12 scale where lower is better.
Time Frame	through day 7 of mechanical ventilation or initial extubation (whichever is first)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Up to 28 days or until discharge from the ICU (whichever is first)
Adverse Event Reporting Description	No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.
Arm/Group Title	Fen. SOC+Saline Placebo (Bolus+Infusion)		Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr)		Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr)		Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr)
Arm/Group Description	Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion) Fentanyl: Fentanyl standard of care		Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.2 mcg/kg/hr)		Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.5 mcg/kg/hr)		Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.7 mcg/kg/hr)
All Cause Mortality
	Fen. SOC+Saline Placebo (Bolus+Infusion)		Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr)		Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr)		Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/12 (0%)		0/12 (0%)		0/0 (NaN)
Serious Adverse Events
	Fen. SOC+Saline Placebo (Bolus+Infusion)		Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr)		Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr)		Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		2/12 (16.7%)		1/12 (8.3%)		0/0 (NaN)
Gastrointestinal disorders
Colitis (excl infective)	0/6 (0%)		1/12 (8.3%)	1	0/12 (0%)	1	0/0 (NaN)	1
General disorders
General signs and symptoms NEC	0/6 (0%)		1/12 (8.3%)	1	0/12 (0%)	1	0/0 (NaN)	1
Nervous system disorders
Seizures and seizure disorder NEC	0/6 (0%)		0/12 (0%)		1/12 (8.3%)	1	1/0 (Infinity)	1
Other (Not Including Serious) Adverse Events
	Fen. SOC+Saline Placebo (Bolus+Infusion)		Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr)		Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr)		Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/6 (66.7%)		9/12 (75%)		8/12 (66.7%)		0/0 (NaN)
Cardiac disorders
Rate and rhythm disorders NEC	2/6 (33.3%)		5/12 (41.7%)		5/12 (41.7%)		5/0 (Infinity)
Gastrointestinal disorders
Colitis (excl infective)	0/6 (0%)		1/12 (8.3%)		0/12 (0%)		0/0 (NaN)
Nausea and vomiting symptoms	0/6 (0%)		0/12 (0%)		1/12 (8.3%)		1/0 (Infinity)
General disorders
Febrile disorders	2/6 (33.3%)		0/12 (0%)		1/12 (8.3%)		1/0 (Infinity)
General signs and symptoms NEC	0/6 (0%)		1/12 (8.3%)		0/12 (0%)		0/0 (NaN)
Hepatobiliary disorders
Hepatic failure and associated disorders	0/6 (0%)		1/12 (8.3%)		0/12 (0%)		0/0 (NaN)
Infections and infestations
Parainfluenzae viral infections	1/6 (16.7%)		0/12 (0%)		0/12 (0%)		0/0 (NaN)
Injury, poisoning and procedural complications
Anaesthetic and allied procedural complications	0/6 (0%)		1/12 (8.3%)		0/12 (0%)		0/0 (NaN)
Respiratory tract and thoracic cavity procedural complications	0/6 (0%)		2/12 (16.7%)		0/12 (0%)		0/0 (NaN)
Investigations
Heart rate and pulse investigations	1/6 (16.7%)		0/12 (0%)		0/12 (0%)		0/0 (NaN)
Metabolism and nutrition disorders
Magnesium metabolism disorders	0/6 (0%)		1/12 (8.3%)		0/12 (0%)		0/0 (NaN)
Protein metabolism disorders NEC	0/6 (0%)		1/12 (8.3%)		0/12 (0%)		0/0 (NaN)
Nervous system disorders
Encephalopathies NEC	0/6 (0%)		1/12 (8.3%)		0/12 (0%)		0/0 (NaN)
Seizures and seizure disorders NEC	0/6 (0%)		0/12 (0%)		1/12 (8.3%)		1/0 (Infinity)
Tremor (excl congenital)	0/6 (0%)		0/12 (0%)		1/12 (8.3%)		1/0 (Infinity)
Psychiatric disorders
Anxiety symptoms	0/6 (0%)		1/12 (8.3%)		0/12 (0%)		0/0 (NaN)
Stereotypies and automatisms	0/6 (0%)		0/12 (0%)		1/12 (8.3%)		1/0 (Infinity)
Renal and urinary disorders
Bladder and urethral symptoms	1/6 (16.7%)		2/12 (16.7%)		1/12 (8.3%)		1/0 (Infinity)
Renal failure and impairment	0/6 (0%)		2/12 (16.7%)		0/12 (0%)		0/0 (NaN)
Respiratory, thoracic and mediastinal disorders
Conditions associated with abnormal gas exchange	0/6 (0%)		1/12 (8.3%)		0/12 (0%)		0/0 (NaN)
Laryngeal spasm, oedema and obstruction	1/6 (16.7%)		0/12 (0%)		0/12 (0%)		0/0 (NaN)
Pneumothorax and pleural effusions NEC	0/6 (0%)		1/12 (8.3%)		1/12 (8.3%)		1/0 (Infinity)
Vascular disorders
Vascular hypotensive disorders	3/6 (50%)		6/12 (50%)		5/12 (41.7%)		5/0 (Infinity)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.