Dexmedetomidine Versus Propofol in the Medical Intensive Care Unit (MICU)

A Double-blinded Randomized Controlled Trial of Dexmedetomidine Versus Propofol for Sedation in Mechanically Ventilated Medical Intensive Care Unit Patients.

This is a randomized controlled trial to compare propofol to dexmedetomidine for prolonged sedation (> 24 hours) in critically ill patients who require mechanical ventilation.

Study Overview

• Status: Terminated
• Conditions: Critical Illness; Mechanical Ventilation
• Intervention / Treatment: Drug: Dexmedetomidine; Drug: Fentanyl; Drug: Midazolam; Behavioral: Physical and Occupational Therapy; Drug: Propofol

Detailed Description

Mechanically ventilated critically ill patients are routinely given sedative and analgesic medications to relieve pain and anxiety associated with intubation, mechanical ventilation, and critical care in general. While integral in minimizing discomfort, these medications may increase mechanical ventilation time, the duration of intensive care unit (ICU) stay, ICU complications (e.g. delirium, ventilator associated pneumonia, venous thromboembolism), the morbidity associated with critical illness, and patient mortality. This study compares two sedative medications that have been used in patients who require a mechanical ventilator. Enrolled patients will be randomly assigned to receive propofol or dexmedetomidine for sedation while they require ventilatory support. All patients will also receive the pain medication fentanyl as needed.

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• >18 years old
• mechanically ventilated through endotracheal tube
• anticipated need for ventilation > 48 hours
• requiring sedative/analgesic medication

Exclusion Criteria:

• on mechanical ventilator > 96 hours
• primary neurologic disease
• post cardiac arrest
• do not speak English (assessment only English language validated)
• pregnancy or lactation
• active myocardial ischemia
• second or third degree heart block
• pancreatitis
• elevated serum triglycerides (> 400 mg/dL)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Dexmedetomidine; Patients in this arm will receive continuous dexmedetomidine infusion (0.2 - 1.5 mcg/kg/hour) titrated to the target Richmond Agitation Sedation Scale for the duration of mechanical ventilation or 7 days on study, whichever is first.	Drug: Dexmedetomidine; continuous IV infusion 0.2 - 1.5 ucg/kg/hour titrated to target RASS; Other Names: Precedex; Drug: Fentanyl; 25 - 200 mcg IV every hour (as multiple IV pushes) as needed titrated to Non-Verbal Pain Scale; Drug: Midazolam; 0.01 - 0.1 mg/kg IV push every 10 minutes as needed for agitation (RASS>+2); Other Names: Versed; Behavioral: Physical and Occupational Therapy; Daily therapy sessions targeting range of motion, strength, and mobility
ACTIVE_COMPARATOR: Propofol; Patients in this arm will receive propofol (5 - 50 mcg/kg/min) for sedation, titrated to the target Richmond Agitation Sedation Scale for the duration of mechanical ventilation or 7 days on study, whichever is first.	Drug: Fentanyl; 25 - 200 mcg IV every hour (as multiple IV pushes) as needed titrated to Non-Verbal Pain Scale; Drug: Midazolam; 0.01 - 0.1 mg/kg IV push every 10 minutes as needed for agitation (RASS>+2); Other Names: Versed; Behavioral: Physical and Occupational Therapy; Daily therapy sessions targeting range of motion, strength, and mobility; Drug: Propofol; continuous IV infusion (5 - 50 ucg/kg/min) titrated to target RASS; Other Names: Diprivan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Days With Delirium	delirium assessment using CAM-ICU	daily up to 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Drug Efficacy According to Richmond Agitation Sedation Scale (RASS) Score	Richmond Agitation Sedation Scale (RASS). This is a validated scale that measures level of sedation. The scale ranges from -5 to +4. -5 refers to a state where one is unarousable, +4 refers to a state where one is combative. The median and inter-quartile range over all daily assessments will be provided.	Daily up to day 28
Number of Patients Completing Mobility Milestones	Milestones: sitting upright independently, standing independently, transfer to chair, marching in place, ambulating independently	Daily through day 28
Days on Ventilator		60 days from enrollment
Days in ICU		60 days from enollment
Mortality		28 days from enrollment
Number of Participants With ICU Complications		daily through day 28
Number of Patients Requiring Fentanyl		during infusion of study medication up to day 28
Number of Patients Requiring Midazolam		during infusion of study medication through day 28
Days in Hospital		60 days from enrollment
Number of Patients Completing Activities of Daily Living	activities of daily living: eating, bathing, dressing, grooming, toileting	daily through day 28
Number of Adverse Medication Effects		duration of infusion of study medication up to 28 days

Collaborators and Investigators

• Sponsor: University of Chicago
• Collaborators: Hospira, now a wholly owned subsidiary of Pfizer

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (ACTUAL): September 1, 2015
• Study Completion (ACTUAL): September 1, 2015

Study Registration Dates

• First Submitted: September 14, 2009
• First Submitted That Met QC Criteria: January 28, 2010
• First Posted (ESTIMATE): February 1, 2010

Study Record Updates

• Last Update Posted (ACTUAL): July 3, 2018
• Last Update Submitted That Met QC Criteria: July 2, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Critical care; Physical therapy; Occupational therapy; Intensive care; Hypnotics and Sedatives; Respiration, Artificial; Ventilators, Mechanical; Sedative medications
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Analgesics, Opioid; Narcotics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Fentanyl; Midazolam; Propofol; Dexmedetomidine
• Other Study ID Numbers: 16865B

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO