Clinical trial NCT00460473: A Research Study to Evaluate the Effectiveness of Dexmedetomidine in Preventing Delirium After Hip Fracture Repair Surgery
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Delirium
Keywords: Mental Health
Neurological Disease
Hip Injuries and Disorders
Lead sponsor: Hospira, now a wholly owned subsidiary of Pfizer
Sponsor class: INDUSTRY
First posted: 2007-04-16
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of subjects who experienced any postoperative delirium up to 3 days after the end of study drug infusion
timeFrame: 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 outcomes:
measure: Duration of postoperative delirium as determined by CAM-ICU up to 3 days after end of study drug infusion
timeFrame: Twice daily (between 6:00-9:00 AM and 5:00-8:00 PM) until 3 days after the end of study drug infusion.
measure: Percentage of subjects who experienced postoperative delirium each day after end of study drug infusion
timeFrame: Twice daily (between 6:00-9:00 AM and 5:00-8:00 PM) until 3 days after the end of study drug infusion.
measure: Perioperative use of all analgesics (Fentanyl, Morphine, and oral analgesics)
timeFrame: During the intraoperative period, Post-anesthesia care unit period and the 3 days Follow-up Period.
measure: Postoperative use of Midazolam
timeFrame: During the PACU period (Approximately 2 hours)
measure: Time-to-Aldrete score of ≥9
timeFrame: Every 15±5 minutes from arrival in the PACU (Approximately 2 hours)
measure: Length of post-operative hospital stay
timeFrame: From the post operative period until subject discharged from hospital
Other outcomes:
Locations:
city: Loma Linda
country: United States
facility: Loma Linda University Medical Center
state: California
city: Los Angeles
country: United States
facility: LAC-USC Medical Center Los Angeles
state: California
city: Pasadena
country: United States
facility: Huntington Memorial Hospital
state: California
city: Miami
country: United States
facility: University of Miami-Jackson Memorial Medical Center
state: Florida
city: Orlando
country: United States
facility: Southeastern Clinical Research Consultants
state: Florida
city: Orlando
country: United States
facility: Orlando Regional Healthcare, Critical Care Medicine
state: Florida
city: Vero Beach
country: United States
facility: G and G Research, Inc.
state: Florida
city: Vero Beach
country: United States
facility: Orthopaedic Center of Vero Beach
state: Florida
city: Augusta
country: United States
facility: Medical College of Georgia
state: Georgia
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics, Dept. of Anesthesia
state: Iowa
city: Louisville
country: United States
facility: Outcomes Research Institute
state: Kentucky
city: Shreveport
country: United States
facility: Louisiana State University, Dept. of Orthopaedic Surgery
state: Louisiana
city: Grand Rapids
country: United States
facility: Spectrum Health Blodgett Campus
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital
state: Michigan
city: Duluth
country: United States
facility: Saint Mary's Duluth Clinic Health System
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic College of Medicine, Dept. of Anesthesiology
state: Minnesota
city: Columbia
country: United States
facility: University of Missouri
state: Missouri
city: Great Neck
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: New York
country: United States
facility: New York University Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center, Presbyterian
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Bellaire
country: United States
facility: Research Concepts
state: Texas
city: Dallas
country: United States
facility: Parkland Health and Hospital System
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Health Systems
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin Medical School, Dept. of Anesthesiology
state: Wisconsin
city: Milwaukee
country: United States
facility: VA Medical Center
state: Wisconsin
Study officials:
References: