Back to resultsDOSE Trial of Opioid Sparing Effect (DOSE)
Primary Purpose
Dexmedetomidine, Mechanical Ventilation Complication, Critically Ill
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Fentanyl
Dexmedetomidine
Dexmedetomidine
Dexmedetomidine
Sponsored by
About this trial
This is an interventional treatment trial for Dexmedetomidine
Eligibility Criteria
Inclusion Criteria:
- Ages 0 to <18 years at the time of enrollment.
- If < 6 months postnatal age, gestational age ≥ 35 weeks.
- Admitted to an intensive care unit.
- Planned or anticipated mechanically ventilation for ≥2 days.
- Require sedation to maintain mechanical ventilation per clinical judgment.
- No contraindication to receipt of fentanyl or dexmedetomidine per clinician judgment.
- Availability and willingness of the parent/legal guardian to provide written informed consent.
Exclusion Criteria:
- Previous participation in this study.
- Severe traumatic brain injury as the underlying etiology for critical illness requiring mechanical ventilation or baseline pediatric cerebral performance category (PCPC) >3.
- Planned receipt of sedatives other than fentanyl or dexmedetomidine.
- Anticipated receipt of neuromuscular blockade for >48 consecutive hours during the study period.
- Receipt of fentanyl or dexmedetomidine via continuous infusion for >12 hours in the 24 hours prior to enrollment.
- Extracorporeal life support (including renal replacement therapy, extracorporeal membrane oxygenation, ventricular assist device, etc.) at the time of enrollment.
- 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)
- Known pregnancy
- Known liver dysfunction, defined as: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2x the upper limit of normal for age
- Known or impending renal failure defined as: anuria > or equal to 12 hours prior to enrollment or requiring renal replacement therapy
- 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)
- 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.
Sites / Locations
- Arkansas Children's Hospital
- University of Florida, Shands Children's Hospital
- Indiana University Health, Riley Hospital for Children
- Our Lady of the Lake Children's Hospital
- UMass Memorial Medical Center, Children's Center
- University of Minnesota Masonic Children's Hospital
- Saint Louis University, Cardinal Glennon Children's Hospital
- University of New Mexico Children's Hospital
- University of Buffalo, Oishei Children's Hospital
- University of Rochester Medical Center, Golisano Children's Hospital
- Duke University Medical Center
- Wake Forest Baptist Medical Center
- Rainbow Babies and Children's Hospital, University Hospitals Cleveland Medical Center
- MetroHealth System, Case CTSA
- Oregon Health and Science University, Doernbecher Children's Hospital
- Drexel University, St. Christopher's Hospital for Children
- Medical University of South Carolina Children's Hospital
- University of Texas - Health Science Center San Antonio
- Primary Children's Medical Center- University of Utah
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Placebo Comparator
Active Comparator
Active Comparator
Active Comparator
Arm Label
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 Description
Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion)
Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion)
Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion)
Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion)
Outcomes
Primary Outcome Measures
Mean Daily Dose of Fentanyl in mcg/kg/hr (Micrograms Per Kilogram Per Hour)
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
Sedation Based on the State Behavior Scale (SBS) Relative to Fentanyl Plasma Concentrations (Cmax)
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.
Sedation Based on SBS Scale Relative to Fentanyl Plasma Concentrations (Cmin)
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.
Sedation Based on SBS Scale Relative to Fentanyl Plasma Concentrations (Css)
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.
Sedation Based on SBS Scale Relative to Fentanyl Plasma Concentrations (AUC)
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.
Sedation Based on SBS Scale Relative to Dexmedetomidine Plasma Concentrations (Cmax)
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.
Sedation Based on SBS Scale Relative to Dexmedetomidine Plasma Concentrations (Cmin)
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.
Sedation Based on SBS Scale Relative to Dexmedetomidine Plasma Concentrations (Css)
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.
Sedation Based on SBS Scale Relative to Dexmedetomidine Plasma Concentrations (AUC)
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.
Sedation Based on Richmond Agitation and Sedation Scale (RASS) Scale Relative to Fentanyl Plasma Concentrations (Cmax)
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.
Sedation Based on RASS Scale Relative to Fentanyl Plasma Concentrations (Cmin)
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.
Sedation Based on RASS Scale Relative to Fentanyl Plasma Concentrations (Css)
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.
Sedation Based on RASS Scale Relative to Fentanyl Plasma Concentrations (AUC)
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.
Sedation Based on RASS Scale Relative to Dexmedetomidine Plasma Concentrations (Cmax)
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.
Sedation Based on RASS Scale Relative to Dexmedetomidine Plasma Concentrations (Cmin)
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.
Sedation Based on RASS Scale Relative to Dexmedetomidine Plasma Concentrations (Css)
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.
Sedation Based on RASS Scale Relative to Dexmedetomidine Plasma Concentrations (AUC)
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.
Number of Participants Experiencing a Clinically Significant Episode of Hypotension
Characterize the safety profile of fentanyl and dexmedetomidine when administered alone or in combination to children receiving mechanical ventilation.
Number of Participants Experiencing SAEs (Serious Adverse Events)
Mean Number of SAEs (Serious Adverse Events) Experienced by Participants
Number of Participants Experiencing a Clinically Significant Episode of Bradycardia
Characterize the safety profile of fentanyl and dexmedetomidine when administered alone or in combination to children receiving mechanical ventilation.
Number of Participants Experiencing a Clinically Significant Episode of Urinary Retention
Characterize the safety profile of fentanyl and dexmedetomidine when administered alone or in combination to children receiving mechanical ventilation.
Full Information
NCT ID
NCT03938857
First Posted
April 25, 2019
Last Updated
October 7, 2021
Sponsor
Duke University
Collaborators
National Institutes of Health (NIH), Johns Hopkins University, Intermountain Health Care, Inc., Vanderbilt University Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT03938857
Brief Title
DOSE Trial of Opioid Sparing Effect
Acronym
DOSE
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2021
Overall Recruitment Status
Terminated
Why Stopped
Enrollment challenging during the pandemic COVID 19
Study Start Date
July 18, 2019 (Actual)
Primary Completion Date
October 21, 2020 (Actual)
Study Completion Date
November 6, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Duke University
Collaborators
National Institutes of Health (NIH), Johns Hopkins University, Intermountain Health Care, Inc., Vanderbilt University Medical Center
4. Oversight
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
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dexmedetomidine, Mechanical Ventilation Complication, Critically Ill
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
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).
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Fen. SOC+saline placebo (bolus+infusion)
Arm Type
Placebo Comparator
Arm Description
Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion)
Arm Title
Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr)
Arm Type
Active Comparator
Arm Description
Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion)
Arm Title
Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr)
Arm Type
Active Comparator
Arm Description
Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion)
Arm Title
Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr)
Arm Type
Active Comparator
Arm Description
Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion)
Intervention Type
Drug
Intervention Name(s)
Fentanyl
Intervention Description
Fentanyl standard of care
Intervention Type
Drug
Intervention Name(s)
Dexmedetomidine
Intervention Description
Dexmedetomidine (0.5 mcg/kg + 0.2 mcg/kg/hr)
Intervention Type
Drug
Intervention Name(s)
Dexmedetomidine
Intervention Description
Dexmedetomidine (0.5 mcg/kg + 0.5 mcg/kg/hr)
Intervention Type
Drug
Intervention Name(s)
Dexmedetomidine
Intervention Description
Dexmedetomidine (0.5 mcg/kg + 0.7 mcg/kg/hr)
Primary Outcome Measure Information:
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)
Secondary Outcome Measure Information:
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
Title
Number of Participants Experiencing SAEs (Serious Adverse Events)
Time Frame
up to 28 days or until discharge from the ICU (whichever is first)
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)
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)
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)
Other Pre-specified Outcome Measures:
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)
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)
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)
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)
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)
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)
10. Eligibility
Sex
All
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Ages 0 to <18 years at the time of enrollment.
If < 6 months postnatal age, gestational age ≥ 35 weeks.
Admitted to an intensive care unit.
Planned or anticipated mechanically ventilation for ≥2 days.
Require sedation to maintain mechanical ventilation per clinical judgment.
No contraindication to receipt of fentanyl or dexmedetomidine per clinician judgment.
Availability and willingness of the parent/legal guardian to provide written informed consent.
Exclusion Criteria:
Previous participation in this study.
Severe traumatic brain injury as the underlying etiology for critical illness requiring mechanical ventilation or baseline pediatric cerebral performance category (PCPC) >3.
Planned receipt of sedatives other than fentanyl or dexmedetomidine.
Anticipated receipt of neuromuscular blockade for >48 consecutive hours during the study period.
Receipt of fentanyl or dexmedetomidine via continuous infusion for >12 hours in the 24 hours prior to enrollment.
Extracorporeal life support (including renal replacement therapy, extracorporeal membrane oxygenation, ventricular assist device, etc.) at the time of enrollment.
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)
Known pregnancy
Known liver dysfunction, defined as: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2x the upper limit of normal for age
Known or impending renal failure defined as: anuria > or equal to 12 hours prior to enrollment or requiring renal replacement therapy
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)
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daniel Benjamin, MD
Organizational Affiliation
Duke Clinical Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Arkansas Children's Hospital
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72202
Country
United States
Facility Name
University of Florida, Shands Children's Hospital
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32608
Country
United States
Facility Name
Indiana University Health, Riley Hospital for Children
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Our Lady of the Lake Children's Hospital
City
Baton Rouge
State/Province
Louisiana
ZIP/Postal Code
70808
Country
United States
Facility Name
UMass Memorial Medical Center, Children's Center
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01655
Country
United States
Facility Name
University of Minnesota Masonic Children's Hospital
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55454
Country
United States
Facility Name
Saint Louis University, Cardinal Glennon Children's Hospital
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63104
Country
United States
Facility Name
University of New Mexico Children's Hospital
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87131
Country
United States
Facility Name
University of Buffalo, Oishei Children's Hospital
City
Buffalo
State/Province
New York
ZIP/Postal Code
14203
Country
United States
Facility Name
University of Rochester Medical Center, Golisano Children's Hospital
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Facility Name
Wake Forest Baptist Medical Center
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
Rainbow Babies and Children's Hospital, University Hospitals Cleveland Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
MetroHealth System, Case CTSA
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44109
Country
United States
Facility Name
Oregon Health and Science University, Doernbecher Children's Hospital
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Drexel University, St. Christopher's Hospital for Children
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19134
Country
United States
Facility Name
Medical University of South Carolina Children's Hospital
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
University of Texas - Health Science Center San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Primary Children's Medical Center- University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84113
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
DOSE Trial of Opioid Sparing Effect
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