A Phase III, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Dexmedetomidine for Sedation During Monitored Anesthesia Care
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 326
- 试验地点
- 27
- 主要终点
- 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
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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.
排除标准
- •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.
研究组 & 干预措施
Dexmedetomidine 0.5 mcg/kg load
干预措施: Dexmedetomidine (Drug)
Dexmedetomidine 1 mcg/kg load
干预措施: Dexmedetomidine (Drug)
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
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
时间窗: 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 \[less than half the eye\])
次要结局
- 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.)
- 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.)
- 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)
- 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)
- Anesthesiologist assessment of subject cooperation(Approximately 24 hours)
- Time from onset of study drug infusion to first dose of rescue midazolam(After the first 15 minutes of study drug infusion)
- 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.)