A Safety and Efficacy Study of Dexmedetomidine in Patients Requiring Sedation for Elective Awake Fiberoptic Intubation

A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study Evaluating the Safety and Efficacy of Dexmedetomidine Used for Sedation During Elective Awake Fiberoptic Intubation

The purpose of this study is to evaluate the safety and efficacy of dexmedetomidine versus placebo used for sedation during elective awake fiberoptic intubation.

An awake fiberoptic intubation is indicated for any patient with an anticipated difficult airway because of their anatomy, airway trauma, morbid obesity, or unstable cervical spine injuries. An awake fiberoptic intubation in a non-sedated patient can be extremely stimulating, uncomfortable, and unpleasant. The clinician must focus on maintaining spontaneous breathing, hemodynamic stability, and the patient's comfort. The term "awake" fiberoptic intubation is used to distinguish this procedure from fiberoptic intubations performed under general anesthesia. Although patients may be sedated for "awake" fiberoptic intubation, they need to be responsive and capable of maintaining their own airway without assistance. Vital components of a successful awake fiberoptic intubation include an anesthesiologist experienced in this technique, adequate topicalization of the airway, and a sedated yet cooperative subject.

Benzodiazepines, combined with opioid, are commonly used for anxiolysis and/or analgesia during awake fiberoptic intubations.

Dexmedetomidine has sympatholytic, sedative, analgesic, and anxiolytic effects that attenuate the catecholamine response to perioperative stress. Dexmedetomidine sedates patients by decreasing sympathetic activity and the level of arousal. Further more, dexmedetomidine has been found to facilitate a decrease in salivary secretion, a desirable effect during fiberoptic intubations.

An estimated 100 subjects (50 DEX, 50 PBO) scheduled for an elective awake fiberoptic intubation because of a potentially difficult airway will be randomized prior to intubation at approximately 18 investigative sites.

Inclusion Criteria:

1. Adult (≥18 years of age);

2. American Society of Anesthesiologists (ASA) score I - IV inclusive;

3. Male or female. 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.

4. Requiring awake fiberoptic (oral or nasal) intubation because of anticipated difficult airway. Subjects must meet at least one of the criteria listed below:

   Criteria for Assessing Difficult Airways

   i. History of difficult intubation

   ii. Anticipated difficult airway

   1. Prominent protruding teeth
   2. Small mouth opening
   3. Narrow mandible
   4. Micrognathia
   5. Macroglossia
   6. Short, muscular neck
   7. Very long neck
   8. Limited neck extension
   9. Congenital airway anomalies
   10. Obesity
   11. Known airway pathology
   12. Known airway malignancy
   13. Upper airway obstruction

   iii. Trauma

   1. Face
   2. Upper airway
   3. Cervical spine

   iv. Anticipated difficult mask ventilation

   v. Severe risk of aspiration

   vi. Respiratory failure

   vii. Severe hemodynamic instability

5. Subject (or subject's legally authorized representative) must voluntarily sign and date the informed consent.

Exclusion Criteria:

1. Previous exposure to any experimental drug within 30 days prior to study drug administration;
2. Central nervous system (CNS) disease with an anticipated increased intracranial pressure or cerebrospinal fluid (CSF) leak;
3. Uncontrolled seizure disorder and/or known psychiatric illness that could confound a normal response to sedative treatment;
4. Presence of acute alcohol intoxication;
5. Current (within 14 days of study entry) treatment with an α2-agonist or antagonist;
6. Subject for whom benzodiazepines, dexmedetomidine or other α2-agonists are contraindicated;
7. Subject received an IV or oral (PO) opioid within one hour or intramuscularly within four hours of the start of study drug administration;
8. Subject has acute unstable angina, laboratory confirmed acute myocardial infarction within the past 6 weeks, heart rate <50 bpm, systolic blood pressure (SBP) <90 mmHg, or complete heart block unless they have a pacemaker.
9. Subject has elevated serum glutamic pyruvate aminotransferase/alanine transaminase (SGPT/ALT) and/or Serum glutamic oxaloacetic transaminase/ aspartate aminotransferase (SGOT/AST) values of ≥2 times the upper limit of normal (ULN).
10. Subject has any other condition or factor which, in the Investigator's opinion, might increase the risk to the subject.