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

Sponsor

Hospira, now a wholly owned subsidiary of Pfizer (Industry)

Overall Status

Completed

CT.gov ID

NCT00398827

Collaborator

(none)

326

Enrollment

Locations

Arms

Duration (Months)

12.1

Patients Per Site

2.4

Patients Per Site Per Month

Study Details

Study Description

Brief 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).

Condition or Disease	Intervention/Treatment	Phase
Anesthesia Surgical Procedures, Elective	Drug: Dexmedetomidine Drug: Placebo	Phase 3

Detailed 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

326 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Dec 1, 2006

Actual Study Completion Date :

May 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dexmedetomidine 0.5 mcg/kg load	Drug: Dexmedetomidine
Experimental: Dexmedetomidine 1 mcg/kg load	Drug: Dexmedetomidine
Placebo Comparator: Placebo	Drug: Placebo

Arm

Intervention/Treatment

Experimental: Dexmedetomidine 0.5 mcg/kg load

Drug: Dexmedetomidine

Experimental: Dexmedetomidine 1 mcg/kg load

Drug: Dexmedetomidine

Placebo Comparator: Placebo

Drug: Placebo

Outcome Measures

Primary Outcome Measures

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 [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.]
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])

Secondary Outcome Measures

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.]
Time from onset of study drug infusion to first dose of rescue midazolam [After the first 15 minutes of study drug infusion]
Subjects who are not adequately sedated (OAA/S is >4) may receive rescue MDZ (after attempting to achieve sedation via study drug titration).
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.]
Time to recovery and readiness for discharge from Post-Anesthesia Care Unit (PACU) [Performed every 15 minutes while the subject is in the PACU until subject is discharged.]
Assessed by time from discontinuation of study drug to reach Aldrete score ≥9.
Total amount of fentanyl required for pain control [After the first 15 minutes of study drug infusion]
Anesthesiologist assessment of ease of management [Approximately 24 hours]
Anesthesiologist assessment of subject cooperation [Approximately 24 hours]
Incidence of post-operative nausea and vomiting (PONV) in the PACU and during the 24 hour follow up [Approximately 24 hours]
Overall Subject satisfaction and anxiety assessed 24 hours after study drug has been discontinued [24 hours after study drug has been discontinued]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

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.
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama	Birmingham	Alabama	United States	35294
2	Loma Linda Medical Center	Loma Linda	California	United States	92354
3	Jackson Memorial Hospital	Miami	Florida	United States	33136
4	University of Miami	Miami	Florida	United States	33136
5	South Miami Hospital	Miami	Florida	United States	33143
6	Johns Hopkins Hospital	Baltimore	Maryland	United States	21287-0712
7	Crossroads Research Inc.	Owings Mills	Maryland	United States	21117
8	Chesapeake Research Group	Pasadena	Maryland	United States	21122
9	Brigham & Women's Hospital	Boston	Massachusetts	United States	02115
10	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
11	William Beaumont Hospital	Royal Oak	Michigan	United States	48073
12	University of Missouri Health Care	Columbia	Missouri	United States	65212
13	NYU School of Medicine	New York	New York	United States	10016
14	Mount Sinai School of Medicine	New York	New York	United States	10029
15	SUNY Upstate Medical Center	Syracuse	New York	United States	13210
16	VAMC	Durham	North Carolina	United States	27705
17	Duke University	Durham	North Carolina	United States	27710
18	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
19	The Ohio State University	Columbus	Ohio	United States	43210-1228
20	University of Pittsburgh	Pittsburgh	Pennsylvania	United States	15261
21	Medical University of South Carolina	Charleston	South Carolina	United States	29425
22	Dallas VA Medical Center	Dallas	Texas	United States	75216
23	Baylor Research Institute	Dallas	Texas	United States	75246
24	MD Anderson Cancer Center	Houston	Texas	United States	77030
25	Scott & White Memorial Hospital	Temple	Texas	United States	76508
26	University of Virginia	Charlottesville	Virginia	United States	22908-0710
27	VA Medical Center	Milwaukee	Wisconsin	United States	53295