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
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 30
- 试验地点
- 19
- 主要终点
- Mean Daily Dose of Fentanyl in mcg/kg/hr (Micrograms Per Kilogram Per Hour)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- — 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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) >
- •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
- •Note: receipt of drugs other than fentanyl or dexmedetomidine for intubation, and receipt of neuromuscular blockage for intubation, will not be considered exclusionary criteria.
研究组 & 干预措施
Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr)
Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion)
干预措施: Dexmedetomidine (Drug)
Fen. SOC+saline placebo (bolus+infusion)
Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion)
干预措施: Fentanyl (Drug)
Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr)
Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion)
干预措施: Fentanyl (Drug)
Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr)
Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion)
干预措施: Dexmedetomidine (Drug)
Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr)
Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion)
干预措施: Fentanyl (Drug)
Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr)
Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion)
干预措施: Dexmedetomidine (Drug)
Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr)
Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion)
干预措施: Fentanyl (Drug)
结局指标
主要结局
Mean Daily Dose of Fentanyl in mcg/kg/hr (Micrograms Per Kilogram Per Hour)
时间窗: 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.
次要结局
- Sedation Based on SBS Scale Relative to Dexmedetomidine Plasma Concentrations (Cmin)(through day 7 of mechanical ventilation or initial extubation (whichever is first))
- Sedation Based on RASS Scale Relative to Fentanyl Plasma Concentrations (Css)(through day 7 of mechanical ventilation or initial extubation (whichever is first))
- Sedation Based on RASS Scale Relative to Fentanyl Plasma Concentrations (Cmin)(through day 7 of mechanical ventilation or initial extubation (whichever is first))
- 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 (Css)(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)(through day 7 of mechanical ventilation or initial extubation (whichever is first))
- Sedation Based on RASS Scale Relative to Dexmedetomidine Plasma Concentrations (Cmax)(through day 7 of mechanical ventilation or initial extubation (whichever is first))
- Number of Participants Experiencing a Clinically Significant Episode of Bradycardia(up to 28 days or until discharge from the ICU (whichever is first))
- Number of Participants Experiencing a Clinically Significant Episode of Urinary Retention(up to 28 days or until discharge from the ICU (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))
- Sedation Based on RASS Scale Relative to Fentanyl Plasma Concentrations (AUC)(through day 7 of mechanical ventilation or initial extubation (whichever is first))
- Sedation Based on RASS Scale Relative to Dexmedetomidine Plasma Concentrations (Cmin)(through day 7 of mechanical ventilation or initial extubation (whichever is first))
- Sedation Based on RASS Scale Relative to Dexmedetomidine Plasma Concentrations (AUC)(through day 7 of mechanical ventilation or initial extubation (whichever is first))
- Mean Number of SAEs (Serious Adverse Events) Experienced by Participants(up to 28 days or until discharge from the ICU (whichever is first))
- Sedation Based on SBS Scale Relative to Dexmedetomidine Plasma Concentrations (AUC)(through day 7 of mechanical ventilation or initial extubation (whichever is first))
- Number of Participants Experiencing a Clinically Significant Episode of Hypotension(up to 28 days or until discharge from the ICU (whichever is first))
- Sedation Based on RASS Scale Relative to Dexmedetomidine Plasma Concentrations (Css)(through day 7 of mechanical ventilation or initial extubation (whichever is first))
- Number of Participants Experiencing SAEs (Serious Adverse Events)(up to 28 days or until discharge from the ICU (whichever is first))