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
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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.
Show all 13Show fewer
- 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
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03938857
- Acronym / sponsor ID
- DOSE / Pro00102267
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Enrollment challenging during the pandemic COVID 19
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), Johns Hopkins University, Intermountain Health Care, Inc., Vanderbilt University Medical Center
- Study start
- 18 Jul 2019 (actual)
- Primary completion
- 21 Oct 2020 (actual)
- Study completion
- 6 Nov 2020 (actual)
- First posted
- 6 May 2019 (actual)
- Results
- Posted 5 Nov 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
- 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).
| Arm | Type | Receives |
|---|---|---|
| Fen. SOC+saline placebo (bolus+infusion) | Placebo comparator | Drug: FentanylFentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion) |
| Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr) | Active comparator | Drug: Fentanyl, Drug: DexmedetomidineFentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion) |
| Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr) | Active comparator | Drug: Fentanyl, Drug: DexmedetomidineFentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion) |
| Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) | Active comparator | Drug: Fentanyl, Drug: DexmedetomidineFentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion) |
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FentanylFentanyl standard of care | Drug | Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr), Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr), Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr), Fen. SOC+saline placebo (bolus+infusion) |
| DexmedetomidineDexmedetomidine (0.5 mcg/kg + 0.2 mcg/kg/hr) | Drug | Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr) |
| DexmedetomidineDexmedetomidine (0.5 mcg/kg + 0.5 mcg/kg/hr) | Drug | Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr) |
| DexmedetomidineDexmedetomidine (0.5 mcg/kg + 0.7 mcg/kg/hr) | Drug | Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) |
Primary outcome
Mean Daily Dose of Fentanyl in mcg/kg/hr (Micrograms Per Kilogram Per Hour)
Time frame: 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.
21 secondary outcomes
Sedation Based on the State Behavior Scale (SBS) Relative to Fentanyl Plasma Concentrations (Cmax)
Time frame: through day 7 of mechanical ventilation or initial extubation (whichever is first)
Sedation Based on SBS Scale Relative to Fentanyl Plasma Concentrations (Cmin)
Time frame: through day 7 of mechanical ventilation or initial extubation (whichever is first)
Sedation Based on SBS Scale Relative to Fentanyl Plasma Concentrations (Css)
Time frame: through day 7 of mechanical ventilation or initial extubation (whichever is first)
Sedation Based on SBS Scale Relative to Fentanyl Plasma Concentrations (AUC)
Time frame: through day 7 of mechanical ventilation or initial extubation (whichever is first)
Sedation Based on SBS Scale Relative to Dexmedetomidine Plasma Concentrations (Cmax)
Time frame: through day 7 of mechanical ventilation or initial extubation (whichever is first)
Sedation Based on SBS Scale Relative to Dexmedetomidine Plasma Concentrations (Cmin)
Time frame: through day 7 of mechanical ventilation or initial extubation (whichever is first)
Sedation Based on SBS Scale Relative to Dexmedetomidine Plasma Concentrations (Css)
Time frame: through day 7 of mechanical ventilation or initial extubation (whichever is first)
Sedation Based on SBS Scale Relative to Dexmedetomidine Plasma Concentrations (AUC)
Time frame: 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)
Time frame: through day 7 of mechanical ventilation or initial extubation (whichever is first)
Sedation Based on RASS Scale Relative to Fentanyl Plasma Concentrations (Cmin)
Time frame: through day 7 of mechanical ventilation or initial extubation (whichever is first)
Sedation Based on RASS Scale Relative to Fentanyl Plasma Concentrations (Css)
Time frame: through day 7 of mechanical ventilation or initial extubation (whichever is first)
Sedation Based on RASS Scale Relative to Fentanyl Plasma Concentrations (AUC)
Time frame: through day 7 of mechanical ventilation or initial extubation (whichever is first)
Sedation Based on RASS Scale Relative to Dexmedetomidine Plasma Concentrations (Cmax)
Time frame: through day 7 of mechanical ventilation or initial extubation (whichever is first)
Sedation Based on RASS Scale Relative to Dexmedetomidine Plasma Concentrations (Cmin)
Time frame: through day 7 of mechanical ventilation or initial extubation (whichever is first)
Sedation Based on RASS Scale Relative to Dexmedetomidine Plasma Concentrations (Css)
Time frame: through day 7 of mechanical ventilation or initial extubation (whichever is first)
Sedation Based on RASS Scale Relative to Dexmedetomidine Plasma Concentrations (AUC)
Time frame: through day 7 of mechanical ventilation or initial extubation (whichever is first)
Number of Participants Experiencing a Clinically Significant Episode of Hypotension
Time frame: up to 28 days or until discharge from the ICU (whichever is first)
Number of Participants Experiencing SAEs (Serious Adverse Events)
Time frame: up to 28 days or until discharge from the ICU (whichever is first)
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)
Number of Participants Experiencing a Clinically Significant Episode of Bradycardia
Time frame: up to 28 days or until discharge from the ICU (whichever is first)
Number of Participants Experiencing a Clinically Significant Episode of Urinary Retention
Time frame: up to 28 days or until discharge from the ICU (whichever is first)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36577492Boutzoukas 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.
- Individual participant dataSharing planned: No
Related trials for Dexmedetomidine
Recruiting
Perioperative Dexmedetomidine and Long-term Survival After Cancer Surgery
Elderly, Cancer Surgery
RecruitingPhase 4
Adding Dexmedetomidine or Clonidine to Spinal Anesthesia for Cesarean Delivery
Cesarean Delivery, Cesarean Delivery; Neuraxial Opioids
Active, not recruitingPhase 1/2
Sublingual Dexmedetomidine for Treating Opioid Withdrawal
Opioid Use Disorder, Opioid Withdrawal
Recruiting
The Effects of Midazolam, Dexmedetomidine, and Esketamine on Bispectral Index and Raw Electroencephalogram in Patients Under Propofol-Remifentanil Baseline Anesthesia
Depth of Anesthesia Monitoring, BIS-EEG
Recruiting
Exploration of Appropriate BIS Range and Propofol Effect-site Concentration During Total Intravenous Anesthesia With Concomitant Adjuvants.
Knee Osteoarthritis, Replacement, Knee
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniel Benjamin, MD principal investigator
Duke Clinical Research Institute
19 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
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.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Daily Dose of Fentanyl in mcg/kg/hr (Micrograms Per Kilogram Per Hour) (time frame: through day 7 of mechanical ventilation or initial extubation (whichever is first)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03938857, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2021.