Dexmedetomidine Versus Midazolam for Facilitating Extubation

Critical Illness Clinical Trial

Official title:

Dexmedetomidine vs. Midazolam for Facilitating Extubation in Medical and Surgical ICU Patients: A Randomized, Double-Blind Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00744380
• Other study ID #: 08-0570
• Status: Completed
• Phase: N/A
• First received: August 28, 2008
• Last updated: March 8, 2016
• Start date: August 2008
• Est. completion date: October 2012

Study information

• Verified date: March 2016
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: October 2012
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

1. 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 .

2. 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.

3. 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.

4. Informed consent and HIPAA authorization within 24 hours of qualifying for daily awakenings.

Exclusion Criteria:

1. Patients < 18 years of age or > 85 years of age.

2. Patients receiving intermittent or "as needed" administration of lorazepam or midazolam.

3. Patients receiving lorazepam or midazolam for purposes other than sedation (e.g. seizure control).

4. Patients receiving epidural administration of medication(s).

5. Patients with Childs-Pugh class C liver disease.

6. Comatose patients by metabolic or neurologic affectation.

7. Patients with active myocardial ischemia or second- or third-degree heart block.

8. Moribund state with planned withdrawal of life support.

9. Patients with known or suspected severe adverse reactions to midazolam (or any other benzodiazepine) or dexmedetomidine (or clonidine).

10. Patients with alcohol abuse within six months of study eligibility.

11. Pregnant females or females suspected of being pregnant.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Critical Illness

Intervention

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)
• 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)

Locations

Country	Name	City	State
United States	University of Colorado Hospital	Aurora	Colorado

Sponsors (2)

Lead Sponsor	Collaborator
University of Colorado, Denver	Hospira, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Comparatively determine the time from study initiation to tracheal extubation with midazolam and dexmedetomidine when the practice of daily awakenings is used.		study duration	Yes
Secondary	Comparatively determine: the doses of conventional sedatives and analgesics		study duration	Yes
Secondary	the quality of sedation and analgesia		study duration	Yes
Secondary	sedation-related adverse effects		study duration	Yes
Secondary	the administration and total costs of sedation		study duration	Yes