A Safety and Efficacy Study of Dexmedetomidine in Patients Requiring Sedation During Monitored Anesthesia Care (MAC)

Anesthesia Clinical Trial

Official title:

A Phase III, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Dexmedetomidine for Sedation During Monitored Anesthesia Care

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00398827
• Other study ID #: 2005-005
• Status: Completed
• Phase: Phase 3
• First received: November 10, 2006
• Last updated: July 22, 2015
• Start date: December 2006
• Est. completion date: May 2007

Study information

• Verified date: July 2015
• Source: Hospira, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The objective of this study is to evaluate the safety and efficacy of dexmedetomidine as compared to placebo when used for the sedation of subjects requiring monitored anesthesia care (MAC).

Description:

Monitored anesthesia care (MAC) is a specific anesthesia service that involves an anesthesiologist administering sedatives and analgesics to a patient while monitoring his/her vital signs. MAC is often used to supplement local and regional anesthesia for non-intubated patients undergoing non-invasive procedures and minor surgery. The goal of MAC is to relieve anxiety by inducing a minimally depressed level of consciousness while the patient is able to continuously and independently maintain a patent airway and to respond appropriately to verbal commands.

Respiratory depression is the major concern with most of the medications (midazolam, fentanyl, propofol) currently used for MAC. There is clearly an unmet need for a sedative agent that can safely be used during MAC in both healthy and high risk populations with limited adverse side effects. A medication that can attenuate anxiety and the stress response associated with surgery and procedures without causing respiratory depression is highly desirable. A medication that reduces the total amount of opioids administered during a procedure could substantially reduce complications. Such a medication could be used either alone or in combination with other agents, thereby reducing the dose and side effects of the other agents.

Dexmedetomidine (DEX) has sympatholytic, sedative, analgesic, and anxiolytic effects that attenuate the catecholamine response to perioperative stress. DEX has not been associated with respiratory depression when used alone, despite sometimes deep levels of sedation.

An estimated 325 patients (260 DEX, 65 PBO) requiring MAC sedation for an elective surgery/procedure will be randomized at approximately 25 investigative sites.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 326
• Est. completion date: May 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult (=18 years of age)

• American Society of Anesthesiologists (ASA) Physical Status I, II, III, or IV.

• If female, subject is non-lactating and is either:

1. Not of childbearing potential, defined as post-menopausal for at least 1 year or surgically sterile due to bilateral tubal ligation, bilateral oophorectomy or hysterectomy.

2. Of childbearing potential but is not pregnant at time of baseline and is practicing one of the following methods of birth control: oral or parenteral contraceptives, double-barrier method, vasectomized partner, or abstinence from sexual intercourse.

• Subject requires monitored anesthesia care (MAC) in an operating room (OR) or procedure room with an anesthesiologist in attendance.

• Subject requires one of the following types of elective surgeries/procedures expected to take longer than 30 minutes:

• Orthopedic

• Ophthalmic

• Plastic

• Vascular stents

• Breast biopsies

• AV fistulas

• Excision of lesion.

• Subject requires local anesthetic block.

• Subject (or subject's legally authorized representative) has voluntarily signed and dated the informed consent document approved by the Institutional Review Board.

Exclusion Criteria:

• Subject has received general anesthesia within 7 days prior to study entry, has received any experimental drug within 30 days prior to study drug administration, or has been previously enrolled in this study.

• Subject requires endotracheal intubation or laryngeal mask airway (LMA)

• Subject has central nervous system (CNS) disease with an anticipated potential for increased intracranial pressure, an uncontrolled seizure disorder, and/or known psychiatric illness that could confound a normal response to sedative treatment.

• Subject requires epidural or spinal anesthesia.

• Subject has received treatment with an alpha-2 agonist or antagonist within 14 days of the scheduled surgery/procedure.

• Subject for whom opiates, benzodiazepines, dexmedetomidine, or other alpha-2 agonists are contraindicated.

• Subject has received an intravenous (IV) opioid within one hour, or a by mouth (PO)/intramuscular (IM) opioid within 4 hours, of the start of study drug administration.

• Subject has acute unstable angina, acute myocardial infarction documented by laboratory findings in the past 6 weeks, heart rate <50 bpm, systolic blood pressure (SBP) <90 mmHg, or third-degree heart block unless patient has a pacemaker.

• Subject has known elevated serum glutamic pyruvic transaminase (SGPT/Alanine aminotransferase [ALT]) and/or serum glutamic oxaloacetic transaminase (SGOT/aspartate Aminotransferase [AST]) values of =2 times the upper limit of normal within the 2 months prior to screening, and/or a history of liver failure.

• Subject has any other condition or factor which, in the Investigator's opinion, might increase the risk to the subject.

Study Design

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

Related Conditions & MeSH terms

• Anesthesia
• Surgical Procedures, Elective

Intervention

Drug:
• Dexmedetomidine

• Placebo

Locations

Country	Name	City	State
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	University of Alabama	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Brigham & Women's Hospital	Boston	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	University of Missouri Health Care	Columbia	Missouri
United States	The Ohio State University	Columbus	Ohio
United States	Baylor Research Institute	Dallas	Texas
United States	Dallas VA Medical Center	Dallas	Texas
United States	Duke University	Durham	North Carolina
United States	VAMC	Durham	North Carolina
United States	MD Anderson Cancer Center	Houston	Texas
United States	Loma Linda Medical Center	Loma Linda	California
United States	Jackson Memorial Hospital	Miami	Florida
United States	South Miami Hospital	Miami	Florida
United States	University of Miami	Miami	Florida
United States	VA Medical Center	Milwaukee	Wisconsin
United States	Mount Sinai School of Medicine	New York	New York
United States	NYU School of Medicine	New York	New York
United States	Crossroads Research Inc.	Owings Mills	Maryland
United States	Chesapeake Research Group	Pasadena	Maryland
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	William Beaumont Hospital	Royal Oak	Michigan
United States	SUNY Upstate Medical Center	Syracuse	New York
United States	Scott & White Memorial Hospital	Temple	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Hospira, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent of patients not requiring midazolam for rescue sedation based on achieving and/or maintaining an Observer's Assessment of Alertness/Sedation Scale (OAA/S) score =4	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])	Prior to start of study drug, 15 minutes after start of study drug infusion, every 5 minutes thereafter throughout the study drug infusion and every 15 minutes while the subject is in the post anesthesia care unit.	No
Secondary	Total amount (mg) of rescue midazolam required to achieve and/or maintain sedation (OAA/S score =4)		Prior to start of study drug, 15 minutes after start of study drug infusion, every 5 minutes thereafter throughout the study drug infusion and every 15 minutes while the subject is in the post anesthesia care unit.	No
Secondary	Time from onset of study drug infusion to first dose of rescue midazolam	Subjects who are not adequately sedated (OAA/S is >4) may receive rescue MDZ (after attempting to achieve sedation via study drug titration).	After the first 15 minutes of study drug infusion	No
Secondary	Percentage of subjects who convert to alternative sedative and/or anesthetic therapy due to failure of treatment with study drug and rescue		Prior to start of study drug, 15 minutes after start of study drug infusion, every 5 minutes thereafter throughout the study drug infusion and every 15 minutes while the subject is in the post anesthesia care unit.	No
Secondary	Time to recovery and readiness for discharge from Post-Anesthesia Care Unit (PACU)	Assessed by time from discontinuation of study drug to reach Aldrete score =9.	Performed every 15 minutes while the subject is in the PACU until subject is discharged.
Secondary	Total amount of fentanyl required for pain control		After the first 15 minutes of study drug infusion	No
Secondary	Anesthesiologist assessment of ease of management		Approximately 24 hours	No
Secondary	Anesthesiologist assessment of subject cooperation		Approximately 24 hours	No
Secondary	Incidence of post-operative nausea and vomiting (PONV) in the PACU and during the 24 hour follow up		Approximately 24 hours	No
Secondary	Overall Subject satisfaction and anxiety assessed 24 hours after study drug has been discontinued		24 hours after study drug has been discontinued	No