Dexmedetomidine Versus Midazolam for Facilitating Extubation - Full Text View

Sponsors and Collaborators:	University of Colorado at Denver and Health Sciences Center Hospira, Inc.
Information provided by:	University of Colorado at Denver and Health Sciences Center
ClinicalTrials.gov Identifier:	NCT00744380

Purpose

The purpose of this randomized, double-blind study is to evaluate the utility, safety, and cost of transitioning benzodiazepine sedation to dexmedetomidine in medical or surgical intensive care unit (ICU) patients requiring sedation when tracheal extubation is nearing. Fifty medical or surgical ICU patients requiring sedation with existing benzodiazepine therapy and qualifying for daily awakenings will be randomized in a double-blind manner to receive additional midazolam or dexmedetomidine. This study is unique because midazolam or dexmedetomidine will be added, in a blinded fashion, to existing sedation and analgesia in an effort to decrease or possibly discontinue these therapies.

Objectives:

The objectives of this study are to determine if transitioning conventional sedation to dexmedetomidine safely facilitates tracheal extubation after study initiation; alters the amounts of sedative and analgesic agents required after study initiation; influences the levels of sedation and analgesia; alters the adverse event profile (neurologic, hemodynamic, or gastrointestinal) during and after discontinuing sedation; and impacts the total cost of sedation during and after discontinuing sedation. Hypothesis 1: Transitioning conventional sedation to dexmedetomidine expedites tracheal extubation to shorten ventilator time. Specific Aim 1: Comparatively determine the time from study initiation to tracheal extubation with midazolam and dexmedetomidine when the practice of daily awakenings is used. Hypothesis 2: Transitioning conventional sedation to dexmedetomidine reduces the doses of conventional sedatives and analgesics while maintaining equivalent levels of sedation and analgesia and not incurring adverse events. Specific Aim 2a: Comparatively determine the hourly, daily, and cumulative doses of conventional sedatives and analgesics from study initiation to sedation discontinuation with midazolam and dexmedetomidine when the practice of daily awakenings is used. Specific Aim 2b: Comparatively evaluate the quality of sedation and analgesia of midazolam and dexmedetomidine by determining the proportion of Riker sedation scores at 3 - 4 (desired level of sedation) and ≤ 2 or ≥ 5 (undesired levels of sedation) and the proportion of Pain Assessment Behavioral Scores (PABS) ≤ 3 (comfortable) and ≥ 4 (pain). Specific Aim 2c: Comparatively evaluate sedation-related adverse effects (neurologic, hemodynamic, or gastrointestinal) of midazolam and dexmedetomidine when the practice of daily awakenings is used.

Hypothesis 3: Transitioning conventional sedation to dexmedetomidine increases the cost of administering sedation but minimizes the incidental costs associated with sedation to counterbalance and possibly reduce the total cost of sedation (sum of administration costs and incidental costs). Specific Aim 3a: Comparatively determine the hourly, daily, and cumulative administration costs of midazolam and dexmedetomidine when the practice of daily awakenings is used. Specific Aim 3b: Comparatively determine the hourly, daily, and cumulative incidental costs of conventional sedatives and dexmedetomidine; including neurologic dysfunction, antipsychotic requirements, cardiovascular dysfunction, constipation or ileus, differences in times to ventilator discontinuation, personnel time, and patient transfer from the ICU after sedation discontinuation.

Condition	Intervention
Critical Care Sedation	Drug: Midazolam Drug: Dexmedetomidine

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Dexmedetomidine vs. Midazolam for Facilitating Extubation in Medical and Surgical ICU Patients: A Randomized, Double-Blind Study

Resource links provided by NLM:

MedlinePlus related topics: Critical Care Surgery

Drug Information available for: Midazolam Midazolam maleate Midazolam hydrochloride Dexmedetomidine Dexmedetomidine hydrochloride

U.S. FDA Resources

Further study details as provided by University of Colorado at Denver and Health Sciences Center:

Primary Outcome Measures:

Comparatively determine the time from study initiation to tracheal extubation with midazolam and dexmedetomidine when the practice of daily awakenings is used. [ Time Frame: study duration ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Comparatively determine: the doses of conventional sedatives and analgesics [ Time Frame: study duration ] [ Designated as safety issue: Yes ]
the quality of sedation and analgesia [ Time Frame: study duration ] [ Designated as safety issue: Yes ]
sedation-related adverse effects [ Time Frame: study duration ] [ Designated as safety issue: Yes ]
the administration and total costs of sedation [ Time Frame: study duration ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	50
Study Start Date:	August 2008
Estimated Study Completion Date:	December 2010
Estimated Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Mid: Active Comparator Midazolam infusion of 1 mg/hour (final infusion concentration of 0.5 mg/mL) and adjusted by 1 mg/hour by the bedside nurse as needed for the desired level of sedation (Riker sedation-agitation score of 3 - 4)	Drug: Midazolam Midazolam infusion of 1 mg/hour (final infusion concentration of 0.5 mg/mL) and adjusted by 1 mg/hour by the bedside nurse as needed for the desired level of sedation (Riker sedation-agitation score of 3 - 4)
Dex: Experimental Dexmedetomidine 0.15 µg/kg per hour (final infusion concentration of 0.075 µg/kg per mL) and adjusted by 0.15 µg/kg per hour by the bedside nurse as needed for the desired level of sedation (Riker sedation-agitation score of 3 - 4)	Drug: Dexmedetomidine Dexmedetomidine 0.15 µg/kg per hour (final infusion concentration of 0.075 µg/kg per mL) and adjusted by 0.15 µg/kg per hour by the bedside nurse as needed for the desired level of sedation (Riker sedation-agitation score of 3 - 4)

Eligibility

Ages Eligible for Study:	18 Years to 85 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients requiring mechanical ventilation in the medical or surgical ICUs and currently receiving lorazepam or midazolam by continuous infusion for the purpose of sedation therapy. Sedation in these ICUs is provided using an ICU-wide order form that preferentially uses either lorazepam or midazolam with the infusion rate titrated by the bedside nurse to the desired Riker sedation-agitation score(s). Continuous analgesia is provided with fentanyl only with the infusion rate titrated by the bedside nurse to PABS ≤ 3 .
Anticipated duration of continuous sedation > 12 hours with the level of sedation expected to be maintained at Riker sedation-agitation score(s) of 3 - 4.
Patients qualifying for daily awakenings as determined by all of the following: fraction of inspired oxygen (FiO2) ≤ 70% or positive end expiratory pressure (PEEP) ≤ 14 cmH2O, hemodynamically stable, and NOT receiving pharmacologic neuromuscular blockade.
Informed consent and HIPAA authorization within 24 hours of qualifying for daily awakenings.

Exclusion Criteria:

Patients < 18 years of age or > 85 years of age.
Patients receiving intermittent or "as needed" administration of lorazepam or midazolam.
Patients receiving lorazepam or midazolam for purposes other than sedation (e.g. seizure control).
Patients receiving epidural administration of medication(s).
Patients with Childs-Pugh class C liver disease.
Comatose patients by metabolic or neurologic affectation.
Patients with active myocardial ischemia or second- or third-degree heart block.
Moribund state with planned withdrawal of life support.
Patients with known or suspected severe adverse reactions to midazolam (or any other benzodiazepine) or dexmedetomidine (or clonidine).
Patients with alcohol abuse within six months of study eligibility.
Pregnant females or females suspected of being pregnant.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00744380

Contacts

Contact: Robert MacLaren, PharmD

303-724-2622

rob.maclaren@uchsc.edu

Locations

United States, Colorado
University of Colorado Hospital	Recruiting
Aurora, Colorado, United States, 80010
Contact: Robert MacLaren, PharmD 303-724-2622 rob.maclaren@uchsc.edu
Principal Investigator: Rob MacLaren, PharmD

Sponsors and Collaborators

University of Colorado at Denver and Health Sciences Center

Hospira, Inc.

More Information

No publications provided

Responsible Party:	School of Pharmacy, University of Colorado Denver ( Robert MacLaren Associate Professor )
Study ID Numbers:	COMIRB08-0570
Study First Received:	August 28, 2008
Last Updated:	August 29, 2008
ClinicalTrials.gov Identifier:	NCT00744380 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Colorado at Denver and Health Sciences Center:

Analgesia
Mechanical ventilation

Study placed in the following topic categories:

Anesthetics, Intravenous
Neurotransmitter Agents
Adrenergic alpha-Agonists
Tranquilizing Agents
Adrenergic Agents
Adjuvants, Immunologic
Psychotropic Drugs
Anesthetics
Central Nervous System Depressants

Midazolam
Adrenergic Agonists
Analgesics, Non-Narcotic
Anesthetics, General
Hypnotics and Sedatives
Anti-Anxiety Agents
Peripheral Nervous System Agents
Dexmedetomidine
Analgesics

Additional relevant MeSH terms:

Neurotransmitter Agents
Adrenergic Agents
Molecular Mechanisms of Pharmacological Action
GABA Modulators
Physiological Effects of Drugs
Psychotropic Drugs
Anesthetics
Adrenergic Agonists
Sensory System Agents
Therapeutic Uses
Hypnotics and Sedatives
Dexmedetomidine
Analgesics

Anesthetics, Intravenous
Tranquilizing Agents
Adrenergic alpha-Agonists
Central Nervous System Depressants
Midazolam
Pharmacologic Actions
Adjuvants, Anesthesia
Anesthetics, General
Analgesics, Non-Narcotic
GABA Agents
Anti-Anxiety Agents
Peripheral Nervous System Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 10, 2009