DOSE Trial of Opioid Sparing Effect

NCT03938857 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: Pro001022675U24TR001608
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 19

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.

Conditions

Dexmedetomidine; Mechanical Ventilation Complication; Critically Ill

Outcome Measures

Primary Outcomes (1)

• 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.

  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)

  through day 7 of mechanical ventilation or initial extubation (whichever is first)

• Sedation Based on SBS Scale Relative to Fentanyl Plasma Concentrations (Cmin)

  through day 7 of mechanical ventilation or initial extubation (whichever is first)

• Sedation Based on SBS Scale Relative to Fentanyl Plasma Concentrations (Css)

  through day 7 of mechanical ventilation or initial extubation (whichever is first)

• Sedation Based on SBS Scale Relative to Fentanyl Plasma Concentrations (AUC)

  through day 7 of mechanical ventilation or initial extubation (whichever is first)

• Sedation Based on SBS Scale Relative to Dexmedetomidine Plasma Concentrations (Cmax)

  through day 7 of mechanical ventilation or initial extubation (whichever is first)

Other Outcomes (6)

• Average Daily Cornell Assessment of Pediatrics in Delirium (CAPD) Scores

  through day 7 of mechanical ventilation or initial extubation (whichever is first)

• Maximum Daily CAPD Scores

  through day 7 of mechanical ventilation or initial extubation (whichever is first)

• Minimum Daily CAPD Scores

  through day 7 of mechanical ventilation or initial extubation (whichever is first)

Study Arms (4)

Fen. SOC+saline placebo (bolus+infusion)

PLACEBO COMPARATOR

Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion)

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)

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)

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)

Drug: Fentanyl; Drug: Dexmedetomidine

Interventions

Fentanyl DRUG

Fentanyl standard of care

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)

Dexmedetomidine DRUG

Dexmedetomidine (0.5 mcg/kg + 0.2 mcg/kg/hr)

Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr)

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Duke University: lead
• National Institutes of Health (NIH): collaborator
• Johns Hopkins University: collaborator
• Intermountain Health Care, Inc.: collaborator
• Vanderbilt University Medical Center: collaborator

Study Sites (19)

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

Location

University of Florida, Shands Children's Hospital

Gainesville, Florida, 32608, United States

Location

Indiana University Health, Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

Our Lady of the Lake Children's Hospital

Baton Rouge, Louisiana, 70808, United States

Location

UMass Memorial Medical Center, Children's Center

Worcester, Massachusetts, 01655, United States

Location

University of Minnesota Masonic Children's Hospital

Minneapolis, Minnesota, 55454, United States

Location

Saint Louis University, Cardinal Glennon Children's Hospital

St Louis, Missouri, 63104, United States

Location

University of New Mexico Children's Hospital

Albuquerque, New Mexico, 87131, United States

Location

University of Buffalo, Oishei Children's Hospital

Buffalo, New York, 14203, United States

Location

University of Rochester Medical Center, Golisano Children's Hospital

Rochester, New York, 14642, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

Rainbow Babies and Children's Hospital, University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

MetroHealth System, Case CTSA

Cleveland, Ohio, 44109, United States

Location

Oregon Health and Science University, Doernbecher Children's Hospital

Portland, Oregon, 97239, United States

Location

Drexel University, St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, 19134, United States

Location

Medical University of South Carolina Children's Hospital

Charleston, South Carolina, 29425, United States

Location

University of Texas - Health Science Center San Antonio

San Antonio, Texas, 78229, United States

Location

Primary Children's Medical Center- University of Utah

Salt Lake City, Utah, 84113, United States

Location

Related Publications (1)

• 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.

  PMID: 36577492 DERIVED

MeSH Terms

Conditions

Critical Illness

Interventions

Fentanyl; Dexmedetomidine

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Imidazoles; Azoles

Results Point of Contact

• Title: Mara L. Becker, MD, MSCE
• Organization: Duke University

mara.becker@duke.edu

919-613-1942

Study Officials

• Daniel Benjamin, MD

  Duke Clinical Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: April 25, 2019
• First Posted: May 6, 2019
• Study Start: July 18, 2019
• Primary Completion: October 21, 2020
• Study Completion: November 6, 2020
• Last Updated: November 5, 2021
• Results First Posted: November 5, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (19)