Clinical trial NCT00398827: A Safety and Efficacy Study of Dexmedetomidine in Patients Requiring Sedation During Monitored Anesthesia Care (MAC)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Anesthesia
Surgical Procedures, Elective
Keywords: American Society of Anesthesiologists (ASA)
Observer's Assessment of Alertness Scale (OAA/S)
Aldrete Scoring System
Surgery or procedure using monitored care anesthesia
Surgery or procedure at least 30 minutes in duration
Lead sponsor: Hospira, now a wholly owned subsidiary of Pfizer
Sponsor class: INDUSTRY
First posted: 2006-11-14
Enrollment: 326
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: 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.
Secondary outcomes:
measure: Total amount (mg) of rescue midazolam required to achieve and/or maintain sedation (OAA/S score ≤4)
timeFrame: 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.
measure: Time from onset of study drug infusion to first dose of rescue midazolam
timeFrame: After the first 15 minutes of study drug infusion
measure: Percentage of subjects who convert to alternative sedative and/or anesthetic therapy due to failure of treatment with study drug and rescue
timeFrame: 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.
measure: Time to recovery and readiness for discharge from Post-Anesthesia Care Unit (PACU)
timeFrame: Performed every 15 minutes while the subject is in the PACU until subject is discharged.
measure: Total amount of fentanyl required for pain control
timeFrame: After the first 15 minutes of study drug infusion
measure: Anesthesiologist assessment of ease of management
timeFrame: Approximately 24 hours
measure: Anesthesiologist assessment of subject cooperation
timeFrame: Approximately 24 hours
measure: Incidence of post-operative nausea and vomiting (PONV) in the PACU and during the 24 hour follow up
timeFrame: Approximately 24 hours
measure: Overall Subject satisfaction and anxiety assessed 24 hours after study drug has been discontinued
timeFrame: 24 hours after study drug has been discontinued
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Loma Linda
country: United States
facility: Loma Linda Medical Center
state: California
city: Miami
country: United States
facility: Jackson Memorial Hospital
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Miami
country: United States
facility: South Miami Hospital
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Owings Mills
country: United States
facility: Crossroads Research Inc.
state: Maryland
city: Pasadena
country: United States
facility: Chesapeake Research Group
state: Maryland
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Royal Oak
country: United States
facility: William Beaumont Hospital
state: Michigan
city: Columbia
country: United States
facility: University of Missouri Health Care
state: Missouri
city: New York
country: United States
facility: NYU School of Medicine
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical Center
state: New York
city: Durham
country: United States
facility: VAMC
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: Dallas VA Medical Center
state: Texas
city: Dallas
country: United States
facility: Baylor Research Institute
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Temple
country: United States
facility: Scott & White Memorial Hospital
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Milwaukee
country: United States
facility: VA Medical Center
state: Wisconsin
Study officials:
References: