A Research Study to Evaluate the Effectiveness of Dexmedetomidine in Preventing Delirium After Hip Fracture Repair 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 Surgery for Fractured Hip With General Anesthesia

The purpose of this study is to evaluate the efficacy and safety of perioperative use of dexmedetomidine in the prevention of postoperative delirium in subjects undergoing surgery for fractured hip with general anesthesia.

Study Overview

• Status: Terminated
• Conditions: Delirium
• Intervention / Treatment: Drug: Placebo; Drug: Dexmedetomidine

Detailed Description

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 morality. There are no drugs that are currently approved to prevent the onset of delirium but dexmedetomidine has the potential to meet this unmet medical need. Hip fractures, unfortunately are frequent occurrences in the elderly population and the elderly are more prone to developing delirium after surgery.

Dexmedetomidine is currently approved for use for 24 hours in patients on ventilators in the ICU. Study participation will last from within 72 hours of surgery to 3 days after surgery, continue throughout surgery and up to 2 hours after surgery. Delirium will be assessed prior to surgery and for 72 hours after surgery. This assessment will consist of questions to determine memory and thought process. At discharge patient's resource utilization will be evaluated and thirty days after surgery questions will be asked regarding quality of life.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Loma Linda, California, United States, 92354
      • Loma Linda University Medical Center
    • Los Angeles, California, United States, 90033
      • LAC-USC Medical Center Los Angeles
    • Pasadena, California, United States, 91105
      • Huntington Memorial Hospital
  • Florida
    • Miami, Florida, United States, 33101
      • University of Miami-Jackson Memorial Medical Center
    • Orlando, Florida, United States, 32804
      • Southeastern Clinical Research Consultants
    • Orlando, Florida, United States, 32806
      • Orlando Regional Healthcare, Critical Care Medicine
    • Vero Beach, Florida, United States, 32960
      • G and G Research, Inc.
    • Vero Beach, Florida, United States, 32960
      • Orthopaedic Center of Vero Beach
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Medical College of Georgia
  • Iowa
    • Iowa City, Iowa, United States, 52242-1053
      • University of Iowa Hospitals and Clinics, Dept. of Anesthesia
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Outcomes Research Institute
  • Louisiana
    • Shreveport, Louisiana, United States, 71103
      • Louisiana State University, Dept. of Orthopaedic Surgery
  • Michigan
    • Grand Rapids, Michigan, United States, 49506-2810
      • Spectrum Health Blodgett Campus
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital
  • Minnesota
    • Duluth, Minnesota, United States, 55805
      • Saint Mary's Duluth Clinic Health System
    • Rochester, Minnesota, United States, 55906
      • Mayo Clinic College of Medicine, Dept. of Anesthesiology
  • Missouri
    • Columbia, Missouri, United States, 65212
      • University of Missouri
  • New York
    • Great Neck, New York, United States, 11021
      • Mount Sinai School of Medicine
    • New York, New York, United States, 10016
      • New York University Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation
    • Columbus, Ohio, United States, 43210
      • Ohio State University Medical Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center
    • Pittsburgh, Pennsylvania, United States, 15213-2582
      • University of Pittsburgh Medical Center, Presbyterian
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Bellaire, Texas, United States, 77401
      • Research Concepts
    • Dallas, Texas, United States, 75390-9179
      • Parkland Health and Hospital System
  • Virginia
    • Charlottesville, Virginia, United States, 22908-0710
      • University of Virginia Health Systems
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Medical School, Dept. of Anesthesiology
    • Milwaukee, Wisconsin, United States, 53295
      • VA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adult (≥18 years old) male or female who will undergo surgery for fractured hip with general anesthesia within 72 hours of admission to hospital.

2. 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.
3. Subject is American Society of Anesthesiologists Physical Status I, II, III, or IV.
4. 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:

1. Cognitive function level by Mini Mental State Exam (MMSE) of ≤20.
2. Subject has a positive CAM-ICU result for delirium at Screening or Baseline.
3. Subject requires chronic antipsychotic therapy.
4. Subject is anticipated to require additional surgical procedures during the 72 hour Screening Period and the 3 days Follow-up Period.
5. Subject is anticipated to require repair of pelvic fractures (eg,acetabulum).
6. 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.
7. Subject known to be in liver failure.
8. 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.
9. Subject has received treatment with a α2-agonist or antagonist (within 14 days of study entry).
10. Subject for whom opiates, benzodiazepines, DEX or other α2-agonists are contraindicated.
11. Subject has, per the investigator's judgment, a known or suspected physical or psychological dependence on an abused drug, other than alcohol.
12. Subject has acute unstable angina, acute myocardial infarction, HR <50 bpm, SBP <90 mmHg, or third degree heart block unless the subject has a pacemaker.
13. Subject has any condition or factor which, in the Investigator's opinion, might increase the risk to the subject.
14. Subject is not expected to live more than 60 days.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Dexmedetomidine	Drug: Dexmedetomidine
PLACEBO_COMPARATOR: Placebo (PBO)	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of subjects who experienced any postoperative delirium up to 3 days after the end of study drug infusion	The presence of postoperative delirium will be determined by Confusion Assessment Method for the Intensive Care Unit (CAM-ICU).	Twice daily (between 6:00-9:00 AM and 5:00-8:00 PM) until 3 days after the end of study drug infusion.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of postoperative delirium as determined by CAM-ICU up to 3 days after end of study drug infusion		Twice daily (between 6:00-9:00 AM and 5:00-8:00 PM) until 3 days after the end of study drug infusion.
Percentage of subjects who experienced postoperative delirium each day after end of study drug infusion		Twice daily (between 6:00-9:00 AM and 5:00-8:00 PM) until 3 days after the end of study drug infusion.
Perioperative use of all analgesics (Fentanyl, Morphine, and oral analgesics)		During the intraoperative period, Post-anesthesia care unit period and the 3 days Follow-up Period.
Postoperative use of Midazolam	If RASS >0, midazolam (MDZ) 0.5-1 mg IV will be given until RASS <0. While in PACU during study drug infusion period, MDZ (0.5-1 mg IV) will be given if RASS >+1 under allowed maximum dose of study drug. RASS range: +4 Combative -Overtly combative, violent, immediate danger to staff; +3 Very agitated- Pulls or removes tubes or catheters, aggressive; +2 Agitated- Frequent non-purposeful movements, fights ventilator; +1 Restless- Anxious, but movements not aggressive or vigorous; 0 Alert and calm; -1 Drowsy - Not fully alert, but sustained awakening (eye opening, eye contact) to voice (>10 sec); -2 Light sedation - Briefly awakens with eye contact to voice (<10 sec); -3 Moderate sedation - Movement or eye opening to voice (but no eye contact); -4 Deep sedation No response to voice, but movement or eye opening to physical stimulation; -5 Unarousable No response to voice or physical stimulation	During the PACU period (Approximately 2 hours)
Time-to-Aldrete score of ≥9	A score of 9-10 indicates the subject has recovered from anesthesia and is ready for discharge from the PACU.	Every 15±5 minutes from arrival in the PACU (Approximately 2 hours)
Length of post-operative hospital stay		From the post operative period until subject discharged from hospital

Collaborators and Investigators

• Sponsor: Hospira, now a wholly owned subsidiary of Pfizer

Study record dates

Study Major Dates

• Study Start: April 1, 2007
• Primary Completion (ACTUAL): November 1, 2007
• Study Completion (ACTUAL): November 1, 2007

Study Registration Dates

• First Submitted: April 13, 2007
• First Submitted That Met QC Criteria: April 13, 2007
• First Posted (ESTIMATE): April 16, 2007

Study Record Updates

• Last Update Posted (ESTIMATE): July 24, 2015
• Last Update Submitted That Met QC Criteria: July 23, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: Mental Health; Neurological Disease; Hip Injuries and Disorders
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Dexmedetomidine
• Other Study ID Numbers: DEX-06-09