DOSE Trial of Opioid Sparing Effect

NCT ID: NCT03938857

Last Updated: 2021-11-05

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-07-18

Study Completion Date

2020-11-06

Brief Summary

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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

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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.

Conditions

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Dexmedetomidine Mechanical Ventilation Complication Critically Ill

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

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 Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Fen. SOC+saline placebo (bolus+infusion)

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

Group Type PLACEBO_COMPARATOR

Fentanyl

Intervention Type DRUG

Fentanyl standard of care

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

Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion)

Group Type ACTIVE_COMPARATOR

Fentanyl

Intervention Type DRUG

Fentanyl standard of care

Dexmedetomidine

Intervention Type DRUG

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

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

Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion)

Group Type ACTIVE_COMPARATOR

Fentanyl

Intervention Type DRUG

Fentanyl standard of care

Dexmedetomidine

Intervention Type DRUG

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

Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr)

Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion)

Group Type ACTIVE_COMPARATOR

Fentanyl

Intervention Type DRUG

Fentanyl standard of care

Dexmedetomidine

Intervention Type DRUG

Dexmedetomidine (0.5 mcg/kg + 0.7 mcg/kg/hr)

Interventions

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Fentanyl

Fentanyl standard of care

Intervention Type DRUG

Dexmedetomidine

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

Intervention Type DRUG

Dexmedetomidine

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

Intervention Type DRUG

Dexmedetomidine

Dexmedetomidine (0.5 mcg/kg + 0.7 mcg/kg/hr)

Intervention Type DRUG

Eligibility Criteria

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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.
Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institutes of Health (NIH)

NIH

Sponsor Role collaborator

Johns Hopkins University

OTHER

Sponsor Role collaborator

Intermountain Health Care, Inc.

OTHER

Sponsor Role collaborator

Vanderbilt University Medical Center

OTHER

Sponsor Role collaborator

Duke University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Daniel Benjamin, MD

Role: PRINCIPAL_INVESTIGATOR

Duke Clinical Research Institute

Locations

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Arkansas Children's Hospital

Little Rock, Arkansas, United States

Site Status

University of Florida, Shands Children's Hospital

Gainesville, Florida, United States

Site Status

Indiana University Health, Riley Hospital for Children

Indianapolis, Indiana, United States

Site Status

Our Lady of the Lake Children's Hospital

Baton Rouge, Louisiana, United States

Site Status

UMass Memorial Medical Center, Children's Center

Worcester, Massachusetts, United States

Site Status

University of Minnesota Masonic Children's Hospital

Minneapolis, Minnesota, United States

Site Status

Saint Louis University, Cardinal Glennon Children's Hospital

St Louis, Missouri, United States

Site Status

University of New Mexico Children's Hospital

Albuquerque, New Mexico, United States

Site Status

University of Buffalo, Oishei Children's Hospital

Buffalo, New York, United States

Site Status

University of Rochester Medical Center, Golisano Children's Hospital

Rochester, New York, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, United States

Site Status

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

Cleveland, Ohio, United States

Site Status

MetroHealth System, Case CTSA

Cleveland, Ohio, United States

Site Status

Oregon Health and Science University, Doernbecher Children's Hospital

Portland, Oregon, United States

Site Status

Drexel University, St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, United States

Site Status

Medical University of South Carolina Children's Hospital

Charleston, South Carolina, United States

Site Status

University of Texas - Health Science Center San Antonio

San Antonio, Texas, United States

Site Status

Primary Children's Medical Center- University of Utah

Salt Lake City, Utah, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 36577492 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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5U24TR001608

Identifier Type: NIH

Identifier Source: secondary_id

View Link

Pro00102267

Identifier Type: -

Identifier Source: org_study_id