A Research Study to Evaluate the Effectiveness of Dexmedetomidine in Preventing Delirium After Heart Surgery

A Phase III, Randomized, Double-Blind, Placebo-Controlled, Two-Arm Parallel, Multicenter Study Evaluating the Efficacy and Safety of Dexmedetomidine in the Prevention of Postoperative Delirium in Subjects Undergoing Heart Surgery With Cardiopulmonary Bypass

The purpose of this study is to evaluate the efficacy and safety of dexmedetomidine in the prevention of postoperative delirium in subjects undergoing heart valve surgery with or without coronary artery bypass surgery (CABG) using cardiopulmonary bypass (CPB).

Postoperative delirium is an acute decline in cognition and attention which is usually transient but when delirium persists, it can impact cognitive function, morbidity and mortality. Currently, there are no drugs to prevent delirium but dexmedetomidine has the potential to meet this unmet medical need.

Dexmedetomidine is currently approved for use for 24 hours in patients on ventilators in the Intensive Care Unit(ICU). This study is to determine whether or not dexmedetomidine can prevent delirium after heart surgery. Study participation will last from randomization prior to surgery, to 3 days after surgery. Dexmedetomidine will be given through an intravenous catheter beginning at sternal closure and continue throughout the stay in the ICU. Delirium will be assessed prior to surgery and for 72 hours after surgery. This assessment will consist of questions that will evaluate memory and thought process. Thirty days after surgery, questions will be asked regarding the patients feelings about their health status and hospital billing information will be collected.

Inclusion Criteria:

• Adult (≥18 years old) male or female who will undergo elective heart valve surgery (with or without CABG and using CPB) with general anesthesia and require an overnight stay in the ICU following surgery.

• 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, doublebarrier method, vasectomized partner, or abstinence from sexual intercourse.

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

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

Exclusion Criteria:

• Cognitive function level by Mini Mental State Exam (MMSE) of ≤ 20 at screening.
• Subject has a positive CAM-ICU result for delirium at Screening.
• Subject requires chronic anti-psychotic therapy.
• Subject has participated in a trial with any experimental drug or experimental implantable device within 30 days prior to the study drug administration, or has ever been enrolled in this study.
• Subject is known to be in liver failure.
• Subject has an anticipated potential for increased intracranial pressure or an uncontrolled seizure disorder or known psychiatric illness that could confound a normal response during study assessment.
• Subject has acute myocardial infarction, HR <50 bpm, SBP <90 mmHg, is hemodynamically unstable requiring systemic inotropic drugs or intra-aortic counterpulsation balloon pump within the last 72 hours.
• Subject is anticipated to require hypothermic circulatory arrest during this surgical procedure.
• Subject has received treatment with a α2-agonist or antagonist (within 14 days of study entry).
• Subject for whom opiates, propofol, Dexmedetomidine or other α2-agonists are contraindicated.
• Subject has, per the investigator's judgment, a known or suspected physical or psychological dependence on an abused drug, other than alcohol.
• Subject has any condition or factor which, in the Investigator's opinion, might increase the risk to the subject.
• Subject is not expected to live more than 60 days.