Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication PRECEDEX is a alpha 2 -adrenergic receptor agonist indicated for: • Sedation of initially intubated and mechanically ventilated adult patients during treatment in an intensive care setting. Administer PRECEDEX by continuous infusion not to exceed 24 hours. ( 1.1 ) • Sedation of non-intubated adult patients prior to and/or during surgical and other procedures. FDA label
Also known as Dexmedetomidine hydrochloride, Dexmedetomidine HCL Injection, Precedex, Dexdor
Dexmedetomidine · 11 trials · 12 indications
The analysis of delirium prevalence will be conducted using a modified Intention-to-Treat (ITT) population, defined as all patients who were randomized and received study drug. The investigators chose a 14 day evaluation period for delirium, because it represents the best balance of gaining valuable clinical information, while maximizing resource utilization, given the average study drug infusion to be 5 days and maximum duration to be 10 days. Thus our follow-up period will cover 9 additional days of delirium monitoring after the study drug is stopped in the majority of our patients.
Percentage of participants who did not require rescue medication for Sedation (Midazolam) based on the data of investigator's judgement and State Behavioral Scale (SBS) (which was a sedation assessment instrument for intubated participants and its score ranges from 2 to -3, where 2= agitated, 1= restless and difficult to calm, 0= awake and able to calm, -1= responsive to gentle touch or voice, -2= responsive to noxious stimuli and -3= unresponsive. During intubation \[placement of a flexible plastic tube into the trachea to maintain an open airway or to serve as a conduit through which to administer certain drugs\], the target sedation depth by SBS was -2 to 0, where higher score indicated more responsive and after extubation \[removal of endotracheal tube\], the target sedation depth was -1 to 0, where higher score indicated more responsive) were reported.
Clinical Score Level of Sedation 0 Awake/Alert 1. Minimally Sedated: Tired/sleepy, appropriate response to verbal conversation and/or sounds. 2. Moderately Sedated: Somnolent/sleeping, easily aroused with light tactile stimulation. 3. Deeply sedated: Deep sleep, arousable only with significant physical stimulation. 4. Unarousable
Definition: * Hypotension: dosing start or dose increase of vasopressor drug or use of fluid bolus ≥500 mL within 1 hour resulting from SBP\<60mmHg, DBP\<40mmHg or ≥50% lower than baseline. * Hypertension: dosing start or dose increase of intravenous anti-hypertensive medication resulting from SBP\>160, DBP\>100 or. ≥50% higher than baseline. * Bradycardia: dosing start or dose increase of positive chronotropic medication or use of pacemaker resulting from heart rate \<40bpm or ≥50% lower than baseline.
Observer's Assessment of Alertness/Sedation Scale (OAA/S) score ≤4 (Responsiveness: Lethargic response to name spoken in normal tone; Speech: Mild slowing or thickening; Facial Expression: Mild relaxation; Eyes: Glazed or mild ptosis \[less than half the eye\])
Sedation levels (Ramsay Sedation Scale \[RSS\] score ≥2 \[Patient is cooperative, oriented and tranquil\])
Area under the plasma concentration-time curve of dexmedetomidine at 0 to Infinity hours
Maximum observed concentration of dexmedetomidine in plasma
Concentration of dexmedetomidine at steady state in plasma
Terminal elimination half-life of dexmedetomidine. Half-life is the time required for plasma concentration of the drug to decrease by 50%.
Observed time to reach maximum plasma concentration of dexmedetomidine, expressed in hours
Weight-Adjusted Plasma Clearance of dexmedetomidine after intravenous administration.
Clearance of dexmedetomidine after intravenous administration. Clearance is the rate at which the drug is removed from the plasma after the dose.
Volume of distribution of dexmedetomidine after intravenous administration. Volume of distribution measures how much the drug spreads through the body after the dose.
Weight-Adjusted Volume of distribution of dexmedetomidine after intravenous administration.
FLACC scale is a 5 category observational measure to assess pediatric pain on face, legs, activity, cry and consolability. Responses in each category are scored between 0 to 2 (0 = normal, relaxed to 2 = upset, rigid), for a maximum total score of 10.
The level of sedation will be assessed using the University of Michigan Sedation Scale (UMSS). Score 0 (awake/alert); Score 1 (sleepy/responds appropriately); Score 2 (somnolent/arouses to light stimuli); Score 3 (deep sleep/arouses to deeper physical stimuli); Score 4 (unarousable). The UMSS scores obtained just prior the loading dose (LD) and 5 and 10 minutes during LD; 0, 5, 10, 15, 30, and 60 minutes and thereafter every 4 hours of the maintenance infusion; within 5 minutes of obtaining each pharmacokinetic sample; within 5 minutes prior and after any midazolam rescue during dexmedetomidine infusion period.
Participants who received rescue medication midazolam for sedation and/or fentanyl for analgesic during study drug Infusion
Area under the concentration-time curve from time zero to the time of the last measurable concentration (AUC0-t) for Dexmedetomidine
Area under the concentration-time curve from time zero to the time infinity (AUC0-∞) for Dexmedetomidine
Observed peak plasma concentration (Cmax) for Dexmedetomidine
Plasma concentration at steady state (Css) for Dexmedetomidine
Volume of steady state distribution (Vss) for Dexmedetomidine
Clearance (CL) for Dexmedetomidine
RSS Score range from 1 to 6: 1. Patient is anxious and agitated or restless, or both. 2. Patient is cooperative, orientated and tranquil. 3. Patient responds to command only. 4. Patient exhibits brisk response to light glabellar (between the eyebrows) tap or loud auditory stimulus. 5. Patient exhibits a sluggish response to light glabellar tap or loud auditory stimulus. 6. Patient exhibits no response to stimulus.
Number of subjects who received rescue medication for Sedation (Midazolam) and analgesics (Fentanyl) while intubated during Treatment Period
| Arm | Type | Description |
|---|---|---|
| Dexmedetomidine | ACTIVE_COMPARATOR | Route and Concentration. The study drug will be administered intravenously (IV) by continuous infusion at concentrations of either 4 mcg/mL or 8 mcg/mL dexmedetomidine. Patients will only receive study drug while in the ICU and on mechanical ventilation, and thus will be monitored with continuous telemetry as per usual ICU practice. Dosing Range. Study drug dose will be titrated in a double-blind manner according to clinical effect to achieve a "goal" or "target" Richmond Agitation Sedation Score set by the managing clinical team. For patients in the dexmedetomidine group, dose will range from 0.2-2.0 mcg/kg/hr. |
| Midazolam | ACTIVE_COMPARATOR | Route and Concentration. The study drug will be administered intravenously (IV) by continuous infusion at concentrations of either 0.5 mg/mL or 1 mg/mL midazolam. Patients will only receive study drug while in the ICU and on mechanical ventilation, and thus will be monitored with continuous telemetry as per usual ICU practice. Dosing Range. Study drug dose will be titrated in a double-blind manner according to clinical effect to achieve a "goal" or "target" Richmond Agitation Sedation Score set by the managing clinical team. For patients in the midazolam group, dose will range from 0.025-0.25 mg/kg/hr. |
| DA-9501 | EXPERIMENTAL | A single vial contains an injection solution with 2 mL of dexmedetomidine hydrochloride solution (100 µg/mL as dexmedetomidine) dissolved in physiological saline |
| Placebo | PLACEBO_COMPARATOR | Dexmedetomidine 0 mcg/kg/hr 10 min Initial dose + Dexmedetomidine 0 mcg/kg/hr Maintenance dose |
| Dexmedetomidine 0.067 mcg/kg | EXPERIMENTAL | Dexmedetomidine 0.4 mcg/kg/hr 10 min Initial dose + Dexmedetomidine 0.2 - 0.7 mcg/kg/hr Maintenance dose |
| Dexmedetomidine 0.25 mcg/kg | EXPERIMENTAL | Dexmedetomidine 1.5 mcg/kg/hr 10 min Initial dose + Dexmedetomidine 0.2 - 0.7 mcg/kg/hr Maintenance dose |
| Dexmedetomidine 0.5 mcg/kg | EXPERIMENTAL | Dexmedetomidine 3 mcg/kg/hr 10 min Initial dose + Dexmedetomidine 0.2 - 0.7 mcg/kg/hr Maintenance dose |
| Dexmedetomidine 1.0 mcg/kg | EXPERIMENTAL | Dexmedetomidine 6 mcg/kg/hr 10 min Initial dose + Dexmedetomidine 0.2 - 0.7 mcg/kg/hr Maintenance dose |
| Dexmedetomidine Low Dose | ACTIVE_COMPARATOR | - |
| Dexmedetomidine High dose | ACTIVE_COMPARATOR | - |
| Dexmedetomidine 0.5 mcg/kg load | EXPERIMENTAL | - |
| Dexmedetomidine 1 mcg/kg load | EXPERIMENTAL | - |
| Placebo (PBO) | PLACEBO_COMPARATOR | Placebo load for 10 min and Placebo maintenance for 15 min |
| Dose level 1 | EXPERIMENTAL | Dexmedetomidine 0.7 mcg/kg loading dose and 0.5 mcg/kg/hr maintenance infusion |
| Dose level 2 | EXPERIMENTAL | Dexmedetomidine 1.0 mcg/kg loading dose and 0.75 mcg/kg/hr maintenance infusion |
| Dexmedetomidine 0.05 mcg/kg | EXPERIMENTAL | Dexmedetomidine loading dose 0.05 mcg/kg; maintenance infusion: 0.05 mcg/kg/hr. |
| Dexmedetomidine 0.1 mcg/kg | EXPERIMENTAL | Dexmedetomidine loading dose: 0.1 mcg/kg; maintenance infusion 0.1 mcg/kg/hr. |
| Dexmedetomidine 0.2 mcg/kg | EXPERIMENTAL | Dexmedetomidine loading dose 0.2 mcg/kg; maintenance infusion 0.2 mcg/kg/hr. |
| Group 1 | OTHER | Dose level 1 |
| Group 2 | OTHER | Dose level 2 |
| Group 3 | OTHER | Dose level 3 |
| Group 4 | OTHER | Dose level 4 |
| Name | Type | Description |
|---|---|---|
| Dexmedetomidine | DRUG | For patients in the dexmedetomidine group, dose will range from 0.2-2.0 mcg/kg/hr. For example, a 10 kg patient on an infusion of 1 mcg/kg/hr of dexmedetomidine would receive 10 mcg of study drug per hour. This dose range have been selected after literature review and discussions with critical care practitioners, investigational pharmacists, and the mini-MENDS study steering committee. |
| Midazolam | DRUG | For patients in the midazolam group, dose will range from 0.025-0.25 mg/kg/hr. For example, a 10 kg patient on an infusion of 0.15 mg/kg/hr of midazolam would receive 1.5 mg of midazolam per hour. This dose range have been selected after literature review and discussions with critical care practitioners, investigational pharmacists, and the mini-MENDS study steering committee. |
| Dexmedetomidine hydrochloride | DRUG | * 45 weeks CGA to \< 6 years old: Maintenance infusion will be started at 0.2 µg/kg/h. The infusion rate will be adjusted within a range of 0.2 to 1.4 µg/kg/h according to the pediatric subject's sedative state * 6 years old to \< 17 years old: Maintenance infusion will be started at 0.2 µg/kg/h. The infusion rate will be adjusted within a range of 0.2 to 1.0 µg/kg/h according to the pediatric subject's sedative state |
| Placebo | DRUG | - |
| Fentanyl | DRUG | Rescue medication for pain based on UMSS scores |
| Morphine | DRUG | Rescue medication for pain based on UMSS scores. |
| Dexmedetomidine HCL Injection | DRUG | - |
| Fentanyl/Morphine | DRUG | Per package insert, N-PASS scores and investigator discretion. |
| Dexmedetomidine, midazolam; fentanyl | DRUG | Dexmedetomidine for sedation; midazolam for rescue sedation according to label; fentanyl for rescue pain according to the label |
Inclusion Criteria: * Patients will be eligible for enrollment if they are 1) aged 44 weeks post-menstrual age and up to 11 years, 2) planned admission to the pediatric ICU at Monroe Carell Jr. Children's Hospital at Vanderbilt (MCJCHV), and 3) requiring mechanical ventilation (MV) and sedation. Pr...
Dexmedetomidine is used for sedation and anesthesia across several settings, including ICU sedation, procedural sedation, and awake fiberoptic intubation. It is also studied for delirium and for sedation in intubated and mechanically ventilated pediatric subjects. It is a small molecule developed by Pfizer, Inc. (PFE).
Dexmedetomidine targets the alpha-2 adrenergic receptors ADRA2A, ADRA2B, and ADRA2C, where it acts as an agonist. This receptor activity underlies its sedative and anesthetic-sparing effects. It is a small molecule and is not biomarker-selected.
Dexmedetomidine is developed by Pfizer, Inc., which trades under the ticker PFE. Pfizer is the company associated with the clinical development program for this small-molecule sedative agent.
Dexmedetomidine is in Phase 3 development. It is an investigational agent and is not approved for the indications studied in these trials. The program includes five completed trials and one active trial that is not currently recruiting.
Dexmedetomidine has been studied in trials including NCT04801589, a Phase 3 study of goal-directed sedation in mechanically ventilated infants and children; NCT02757625, a Phase 3 pediatric ICU sedation study; NCT01508455, a Phase 2 anesthesia study in preterm subjects; and NCT01438957, a Phase 3 sedation study during epidural or spinal anesthesia without intubation.
No. Dexmedetomidine is sometimes referenced alongside midazolam and fentanyl in combination regimens, and it is also known as Dexmedetomidine hydrochloride or Dexmedetomidine HCL Injection. However, midazolam and fentanyl are separate drugs, not alternative names for Dexmedetomidine.