DexmedetomidinePhase 1DOSENCT03938857
DOSE Trial of Opioid Sparing Effect
A Phase 1 study testing Fentanyl and Dexmedetomidine in people with Dexmedetomidine and Mechanical Ventilation Complication, run by Duke University at 19 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 18 years
- Conditions the study is for
- Dexmedetomidine, Mechanical Ventilation Complication, Critically Ill
- What is being tested?
- Fentanyl and Dexmedetomidine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 19 sitesUnited States
- Study dates
- 18 Jul 2019to 6 Nov 2020
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
19 sites in 1 country.
19 sites in 1 country
United States19 sites
University of New Mexico Children's Hospital
Albuquerque, New Mexico, 87131
Our Lady of the Lake Children's Hospital
Baton Rouge, Louisiana, 70808
University of Buffalo, Oishei Children's Hospital
Buffalo, New York, 14203
Medical University of South Carolina Children's Hospital
Charleston, South Carolina, 29425
Rainbow Babies and Children's Hospital, University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
MetroHealth System, Case CTSA
Cleveland, Ohio, 44109
Duke University Medical Center
Durham, North Carolina, 27705
University of Florida, Shands Children's Hospital
Gainesville, Florida, 32608
Indiana University Health, Riley Hospital for Children
Indianapolis, Indiana, 46202
Arkansas Children's Hospital
Little Rock, Arkansas, 72202
University of Minnesota Masonic Children's Hospital
Minneapolis, Minnesota, 55454
Drexel University, St. Christopher's Hospital for Children
Philadelphia, Pennsylvania, 19134
Oregon Health and Science University, Doernbecher Children's Hospital
Portland, Oregon, 97239
University of Rochester Medical Center, Golisano Children's Hospital
Rochester, New York, 14642
Primary Children's Medical Center- University of Utah
Salt Lake City, Utah, 84113
University of Texas - Health Science Center San Antonio
San Antonio, Texas, 78229
Saint Louis University, Cardinal Glennon Children's Hospital
St Louis, Missouri, 63104
Wake Forest Baptist Medical Center
Winston-Salem, North Carolina, 27157
UMass Memorial Medical Center, Children's Center
Worcester, Massachusetts, 01655
About this study
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
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.
Read the 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.
- Being tested
- Fentanyl, Dexmedetomidine
- Medical subject headings
- Critical Illness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FentanylDrug
Fentanyl standard of care
DexmedetomidineDrug
Dexmedetomidine (0.5 mcg/kg + 0.2 mcg/kg/hr)
DexmedetomidineDrug
Dexmedetomidine (0.5 mcg/kg + 0.5 mcg/kg/hr)
DexmedetomidineDrug
Dexmedetomidine (0.5 mcg/kg + 0.7 mcg/kg/hr)
| Study group | Role | What they receive |
|---|---|---|
| Fen. SOC+saline placebo (bolus+infusion) | Placebo comparator | Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion) Receives: Drug: Fentanyl |
| Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr) | Active comparator | Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion) Receives: Drug: Fentanyl; Drug: Dexmedetomidine |
| Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr) | Active comparator | Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion) Receives: Drug: Fentanyl; Drug: Dexmedetomidine |
| Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) | Active comparator | Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion) Receives: Drug: Fentanyl; Drug: Dexmedetomidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: through day 7 of mechanical ventilation or initial extubation (whichever is first)
Secondary outcomes (21)
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.
Measured: through day 7 of mechanical ventilation or initial extubation (whichever is first)
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.
Measured: through day 7 of mechanical ventilation or initial extubation (whichever is first)
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.
Measured: through day 7 of mechanical ventilation or initial extubation (whichever is first)
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.
Measured: through day 7 of mechanical ventilation or initial extubation (whichever is first)
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.
Measured: through day 7 of mechanical ventilation or initial extubation (whichever is first)
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.
Measured: through day 7 of mechanical ventilation or initial extubation (whichever is first)
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.
Measured: through day 7 of mechanical ventilation or initial extubation (whichever is first)
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.
Measured: through day 7 of mechanical ventilation or initial extubation (whichever is first)
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.
Measured: through day 7 of mechanical ventilation or initial extubation (whichever is first)
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.
Measured: through day 7 of mechanical ventilation or initial extubation (whichever is first)
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.
Measured: through day 7 of mechanical ventilation or initial extubation (whichever is first)
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.
Measured: through day 7 of mechanical ventilation or initial extubation (whichever is first)
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.
Measured: through day 7 of mechanical ventilation or initial extubation (whichever is first)
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.
Measured: through day 7 of mechanical ventilation or initial extubation (whichever is first)
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.
Measured: through day 7 of mechanical ventilation or initial extubation (whichever is first)
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.
Measured: through day 7 of mechanical ventilation or initial extubation (whichever is first)
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.
Measured: up to 28 days or until discharge from the ICU (whichever is first)
Number of Participants Experiencing SAEs (Serious Adverse Events)
Measured: up to 28 days or until discharge from the ICU (whichever is first)
Mean Number of SAEs (Serious Adverse Events) Experienced by Participants
Measured: up to 28 days or until discharge from the ICU (whichever is first)
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.
Measured: up to 28 days or until discharge from the ICU (whichever is first)
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.
Measured: up to 28 days or until discharge from the ICU (whichever is first)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2019
- Study start18 Jul 2019
- Primary completion21 Oct 2020
- Study completion6 Nov 2020
Why it stopped: Enrollment challenging during the pandemic COVID 19
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for DexmedetomidineStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- 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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), Johns Hopkins University, Intermountain Health Care, Inc., Vanderbilt University Medical Center
- Responsible party
- Sponsor
- Investigators
- Daniel Benjamin, MD, Principal investigator, Duke Clinical Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03938857
- Sponsor's protocol ID
- Pro00102267
- Other IDs
- 5U24TR001608
- Acronym
- DOSE
- Status last verified
- Oct 2021
- First submitted
- 25 Apr 2019
- Last updated
- 5 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Boutzoukas AE, Olson R, Sellers MA, Fischer G, Hornik CD, Alibrahim O, Iheagwara K, Abulebda K, Bass AL, Irby K, Subbaswamy A, Zivick EE, Sweney J, Stormorken AG, Barker EE, Lutfi R, McCrory MC, Costello JM, Ackerman KG, Munoz Pareja JC, Dean JM, Abdelsamad N, Hanley DF Jr, Mould WA, Lane K, Stroud M, Feger BJ, Greenberg RG, Smith PB, Benjamin DK Jr, Hornik CP, Zimmerman KO, Becker ML. Mechanisms to expedite pediatric clinical trial site activation: The DOSE trial experience. Contemp Clin Trials. 2023 Feb;125:107067. doi: 10.1016/j.cct.2022.107067. Epub 2022 Dec 25.
PubMed 36577492