Critically Ill, Dexmedetomidine, Mechanical Ventilation Complication
Conditions
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.
Interventions
DRUGFentanyl
Fentanyl standard of care
DRUGDexmedetomidine
Dexmedetomidine (0.5 mcg/kg + 0.2 mcg/kg/hr)
Sponsors
National Institutes of Health (NIH)
Johns Hopkins University
Intermountain Health Care, Inc.
Vanderbilt University Medical Center
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
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).
Eligibility
Sex/Gender
ALL
Age
No minimum to 18 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| Number of Participants Experiencing SAEs (Serious Adverse Events) | up to 28 days or until discharge from the ICU (whichever is first) | — |
| Mean Number of SAEs (Serious Adverse Events) Experienced by Participants | up to 28 days or until discharge from the ICU (whichever is first) | — |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
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.
Participants by arm
| Arm | Count |
|---|---|
| Fen. SOC+Saline Placebo (Bolus+Infusion) Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion)
Fentanyl: Fentanyl standard of care | 6 |
| Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr) 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) | 12 |
| Fen. SOC+Dex.(.5mcg/kg + .5mcg/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) | 12 |
| Fen. SOC+Dex.(.5mcg/kg + .75mcg/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) | 0 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Physician Decision | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Fen. SOC+Saline Placebo (Bolus+Infusion) | Total | Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr) | Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr) |
|---|---|---|---|---|
| Age, Continuous | 3.8 years STANDARD_DEVIATION 6.8 | 2.8 years STANDARD_DEVIATION 4 | 2.6 years STANDARD_DEVIATION 3.7 | 2.5 years STANDARD_DEVIATION 2.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 26 Participants | 10 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 7 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) White | 3 Participants | 19 Participants | 8 Participants | 8 Participants |
| Region of Enrollment United States | 6 Participants | 30 Participants | 12 Participants | 12 Participants |
| Sex: Female, Male Female | 3 Participants | 12 Participants | 4 Participants | 5 Participants |
| Sex: Female, Male Male | 3 Participants | 18 Participants | 8 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 12 | 0 / 12 | 0 / 0 |
| other Total, other adverse events | 4 / 6 | 9 / 12 | 8 / 12 | 0 / 0 |
| serious Total, serious adverse events | 0 / 6 | 2 / 12 | 1 / 12 | 0 / 0 |
Outcome results
Primary
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.
Time frame: through day 7 of mechanical ventilation or initial extubation (whichever is first)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fen. SOC+Saline Placebo (Bolus+Infusion) | Mean Daily Dose of Fentanyl in mcg/kg/hr (Micrograms Per Kilogram Per Hour) | 2.25 mcg/kg/hr | Standard Deviation 2.15 |
| Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr) | Mean Daily Dose of Fentanyl in mcg/kg/hr (Micrograms Per Kilogram Per Hour) | 2.68 mcg/kg/hr | Standard Deviation 1.53 |
| Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr) | Mean Daily Dose of Fentanyl in mcg/kg/hr (Micrograms Per Kilogram Per Hour) | 3.23 mcg/kg/hr | Standard Deviation 3.3 |
Comparison: Placebo group compared to combined Dexmedetomidine groups.p-value: 0.81495% CI: [-1.035508, 0.8178494]Mixed Models Analysis
Secondary
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)
Population: Participants who experienced at least one SAE. No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr) | Mean Number of SAEs (Serious Adverse Events) Experienced by Participants | 1 serious adverse events | Standard Deviation 0 |
| Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr) | Mean Number of SAEs (Serious Adverse Events) Experienced by Participants | 1 serious adverse events | — |
Secondary
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.
Time frame: up to 28 days or until discharge from the ICU (whichever is first)
Population: Participants with data collected. No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fen. SOC+Saline Placebo (Bolus+Infusion) | Number of Participants Experiencing a Clinically Significant Episode of Bradycardia | 2 Participants |
| Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr) | Number of Participants Experiencing a Clinically Significant Episode of Bradycardia | 3 Participants |
| Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr) | Number of Participants Experiencing a Clinically Significant Episode of Bradycardia | 1 Participants |
Secondary
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.
Time frame: up to 28 days or until discharge from the ICU (whichever is first)
Population: Participants with data collected. No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fen. SOC+Saline Placebo (Bolus+Infusion) | Number of Participants Experiencing a Clinically Significant Episode of Hypotension | 2 Participants |
| Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr) | Number of Participants Experiencing a Clinically Significant Episode of Hypotension | 5 Participants |
| Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr) | Number of Participants Experiencing a Clinically Significant Episode of Hypotension | 3 Participants |
Secondary
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.
Time frame: up to 28 days or until discharge from the ICU (whichever is first)
Population: Participants with data collected. No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fen. SOC+Saline Placebo (Bolus+Infusion) | Number of Participants Experiencing a Clinically Significant Episode of Urinary Retention | 1 Participants |
| Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr) | Number of Participants Experiencing a Clinically Significant Episode of Urinary Retention | 2 Participants |
| Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr) | Number of Participants Experiencing a Clinically Significant Episode of Urinary Retention | 1 Participants |
Secondary
Number of Participants Experiencing SAEs (Serious Adverse Events)
Time frame: up to 28 days or until discharge from the ICU (whichever is first)
Population: No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fen. SOC+Saline Placebo (Bolus+Infusion) | Number of Participants Experiencing SAEs (Serious Adverse Events) | 0 Participants |
| Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr) | Number of Participants Experiencing SAEs (Serious Adverse Events) | 2 Participants |
| Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr) | Number of Participants Experiencing SAEs (Serious Adverse Events) | 1 Participants |
Secondary
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.
Time frame: through day 7 of mechanical ventilation or initial extubation (whichever is first)
Population: Data not collected. The study was terminated early due to enrollment challenges.
Secondary
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.
Time frame: through day 7 of mechanical ventilation or initial extubation (whichever is first)
Population: Data not collected. The study was terminated early due to enrollment challenges.
Secondary
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.
Time frame: through day 7 of mechanical ventilation or initial extubation (whichever is first)
Population: Data not collected. The study was terminated early due to enrollment challenges.
Secondary
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.
Time frame: through day 7 of mechanical ventilation or initial extubation (whichever is first)
Population: Data not collected. The study was terminated early due to enrollment challenges.
Secondary
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.
Time frame: through day 7 of mechanical ventilation or initial extubation (whichever is first)
Population: Data not collected. The study was terminated early due to enrollment challenges.
Secondary
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.
Time frame: through day 7 of mechanical ventilation or initial extubation (whichever is first)
Population: Data not collected. The study was terminated early due to enrollment challenges.
Secondary
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.
Time frame: through day 7 of mechanical ventilation or initial extubation (whichever is first)
Population: Data not collected. The study was terminated early due to enrollment challenges.
Secondary
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.
Time frame: through day 7 of mechanical ventilation or initial extubation (whichever is first)
Population: Data not collected. The study was terminated early due to enrollment challenges.
Secondary
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.
Time frame: through day 7 of mechanical ventilation or initial extubation (whichever is first)
Population: Data not collected. The study was terminated early due to enrollment challenges.
Secondary
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.
Time frame: through day 7 of mechanical ventilation or initial extubation (whichever is first)
Population: Data not collected. The study was terminated early due to enrollment challenges.
Secondary
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.
Time frame: through day 7 of mechanical ventilation or initial extubation (whichever is first)
Population: Data not collected. The study was terminated early due to enrollment challenges.
Secondary
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.
Time frame: through day 7 of mechanical ventilation or initial extubation (whichever is first)
Population: Data not collected. The study was terminated early due to enrollment challenges.
Secondary
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.
Time frame: through day 7 of mechanical ventilation or initial extubation (whichever is first)
Population: Data not collected. The study was terminated early due to enrollment challenges.
Secondary
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.
Time frame: through day 7 of mechanical ventilation or initial extubation (whichever is first)
Population: Data not collected. The study was terminated early due to enrollment challenges.
Secondary
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.
Time frame: through day 7 of mechanical ventilation or initial extubation (whichever is first)
Population: Data not collected. The study was terminated early due to enrollment challenges.
Secondary
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.
Time frame: through day 7 of mechanical ventilation or initial extubation (whichever is first)
Population: Data not collected. The study was terminated early due to enrollment challenges.
Other Pre-specified
Average Daily Cornell Assessment of Pediatrics in Delirium (CAPD) Scores
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)
Other Pre-specified
Average Daily Withdrawal Assessment Tool (WAT-1) Score
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)
Other Pre-specified
Maximum Daily CAPD Scores
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)
Other Pre-specified
Maximum Daily WAT-1 Score
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)
Other Pre-specified
Minimum Daily CAPD Scores
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)
Other Pre-specified
Minimum Daily WAT-1 Score
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)