Purpose

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.

Conditions

Eligibility

Eligible Ages
Under 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. Ages 0 to <18 years at the time of enrollment.
  2. If < 6 months postnatal age, gestational age ≥ 35 weeks.
  3. Admitted to an intensive care unit.
  4. Planned or anticipated mechanically ventilation for ≥2 days.
  5. Require sedation to maintain mechanical ventilation per clinical judgment.
  6. No contraindication to receipt of fentanyl or dexmedetomidine per clinician judgment.
  7. Availability and willingness of the parent/legal guardian to provide written informed consent.

Exclusion Criteria

  1. Previous participation in this study.
  2. Severe traumatic brain injury as the underlying etiology for critical illness requiring mechanical ventilation or baseline pediatric cerebral performance category (PCPC) >3.
  3. Planned receipt of sedatives other than fentanyl or dexmedetomidine.
  4. Anticipated receipt of neuromuscular blockade for >48 consecutive hours during the study period.
  5. Receipt of fentanyl or dexmedetomidine via continuous infusion for >12 hours in the 24 hours prior to enrollment.
  6. Extracorporeal life support (including renal replacement therapy, extracorporeal membrane oxygenation, ventricular assist device, etc.) at the time of enrollment.
  7. Chronic use of or recent overdose of serotonergic agents (selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase (MAO) inhibitors, cyclic antidepressants)
  8. Known pregnancy
  9. Known liver dysfunction, defined as: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2x the upper limit of normal for age
  10. Known or impending renal failure defined as: anuria > or equal to 12 hours prior to enrollment or requiring renal replacement therapy
  11. High risk children, define as: a. known heart block b. known bradyarrythmia including clinically significant bradycardia (defined as requiring chronotropic agents or cardiac pacing to treat)
  12. Receipt of mechanical ventilation during an admission for cardiac surgery

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

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Randomized
Intervention Model
Sequential Assignment
Intervention Model Description
Phase 1b randomized, double-blind, placebo-controlled dose escalation trial. The study will randomize participants to receive placebo (fentanyl standard of care) titrated to sedation+saline placebo (bolus+infusion) or one of the following 3 Dexmedetomidine treatment arms in a sequential cohort fashion: Cohort 1: Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2 mcg/kg/hr infusion); Cohort 2: Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion); Cohort 3: Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion).
Primary Purpose
Treatment
Masking
Triple (Participant, Care Provider, Investigator)

Arm Groups

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

Recruiting Locations

University of Texas - Health Science Center San Antonio
San Antonio, Texas 78229
Contact:
Alvaro Moreira, MD
210-567-7000

More Details

NCT ID
NCT03938857
Status
Recruiting
Sponsor
Duke University

Study Contact

Theresa Jasion
(919)668-8981
theresa.jasion@duke.edu

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.