Study to Evaluate Hemodynamic Effect of Different Loading Doses of Precedex in Post-surgical Intensive Care Unit (ICU) Patients

Phase 4, Open-Label Study Evaluating the Hemodynamic Effect of Differing Loading Regimens of Precedex in a Post-Surgical Intensive Care Patient Population

The objective of this study is to characterize the hemodynamic effects of Precedex (dexmedetomidine (DEX)) during 3 loading-dose paradigms in mechanically ventilated post-surgical subjects in an intensive care setting.

Study Overview

• Status: Completed
• Conditions: Intensive Care Unit
• Intervention / Treatment: Drug: Dexmedetomidine

• Study Type: Observational
• Enrollment (Actual): 373

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1V 4G5
    • Département d'anesthésiologie, Institut universitaire de cardiologie et de pneumologie de Québec
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Foothills Medical Centre, University of Calgary
    • Edmonton, Alberta, Canada, T6G 2G3
      • University of Alberta Hospital, Department of Anesthesiology and Pain Medicine
    • Red Deer, Alberta, Canada, T4N 4E7
      • Red Deer Regional Hospital Centre, Alberta Health Services
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • St. Paul's Hospital
    • Vancouver, British Columbia, Canada, V5Z 1M9
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, 63H 3A7
      • Capital Health-Queen Elizabeth II Health Sciences Center
  • Ontario
    • Kingston, Ontario, Canada, K7L 2V7
      • Kingston General Hospital
    • Kitchener, Ontario, Canada, N2M 1B2
      • St. Mary's General Hospital
    • London, Ontario, Canada, N6A5A5
      • University Hospital
    • Thunder Bay, Ontario, Canada, P7B 7C7
    • Toronto, Ontario, Canada, M56 1W8
      • Department of Anesthesia, St. Michael's Hospital
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital, University Health Network, Department of Anesthesia and Pain Management
  • Quebec
    • Montreal, Quebec, Canada, H3A 1A1
      • McGill University Health Centre (MUHC) Royal Victoria Hospital (RVH)
    • Montreal, Quebec, Canada, H3G 1A4
      • McGill University Health Centre, Montreal General Hospital (MGH)
    • Montreal, Quebec, Canada, H3T 1E2
      • Sir Mortimer B. Davis Jewish General Hospital
    • Sherbrooke, Quebec, Canada, J1H SN4
      • Université de Sherbrooke

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Initially intubated and mechanically ventilated post-surgical adult male and female subjects in an intensive care setting.

Description

Inclusion Criteria:

1. Subject or the subject's legally authorized representative has voluntarily signed and dated the informed consent document approved by the Research Ethics Board (REB).
2. Initially intubated and mechanically ventilated adult post-operative subjects in an intensive care setting (e.g., post operative care unit, post anesthesia care unit, etc.) that are expected to require sedation for at least 2 hours.

3. Has an American Society of Anesthesiologist (ASA) classification of 1, 2, 3 or 4.

   ASA Physical Status Classification System

   • P1 A normal healthy subject
   • P2 A subject with mild systemic disease
   • P3 A subject with severe systemic disease
   • P4 A subject with severe systemic disease that is a constant threat to life
   • P5 A moribund subject who is not expected to survive without the operation
   • P6 A declared brain-dead subject whose organs are being removed for donor purposes.

4. If female, subject must be postmenopausal, surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy), or practicing at least one of the following methods of birth control:

   • hormonal contraceptives (oral, parenteral or transdermal) for at least 3 months prior to study drug administration
   • intrauterine device (IUD)
   • double-barrier method (condoms, contraceptive sponge, diaphragm or vaginal ring with spermicidal jellies or cream).

Exclusion Criteria:

1. Subjects <18 years of age.
2. Subjects with a 2nd degree Mobitz Type II or 3rd degree heart block, unless the subject has a permanent pacemaker or pacing wires are in situ.
3. Subjects with a known allergy to dexmedetomidine.
4. Hypotension based on repeat assessments prior to (within 15 minutes) starting study drug defined as Systolic BP <90 mmHg or Diastolic BP <60 mmHg.
5. Pre-existing bradycardia prior (within 15 minutes) to starting study drug defined as HR <50 bpm.
6. Subjects who, in the opinion of the Investigator, have any other condition where the risks of dexmedetomidine would be expected to outweigh its benefits (e.g., cardiogenic shock on >2 vasopressors, death anticipated within 48 hours).

Study Plan

How is the study designed?

Design Details

• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group I - No loading dose; No loading dose to be administered during the loading-dose paradigms	Drug: Dexmedetomidine
Group II - Loading dose over 10 minutes; Loading dose dexmedetomidine 1 mcg/kg administered over 10 minutes during the loading-dose paradigms	Drug: Dexmedetomidine
Group III - Loading dose over 20 minutes; Loading dose dexmedetomidine 1 mcg/kg administered over 20 minutes during the loading-dose paradigms	Drug: Dexmedetomidine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of clinically meaningful hemodynamic abnormality (CMHA)	Clinically meaningful hemodynamic abnormalities (CMHA) consist of (any): Heart Rate (HR): A native HR <40 bpm (beats per minute); HR <50 bpm requiring pharmacological intervention; systolic BP <80 mm Hg; if pacing wires are in situ, use of a pacemaker after the start of study drug.; Vasoactive Agent Use (i.e. vasopressor or inotrope): the need to add an additional agent to maintain BP; doubling of the dose of any vasoactive agent that was infusing at the start of the study drug.; Paradoxical hypertension: the need to add an additional vasodilating agent for control of hypertension; doubling of the dose of any vasodilating agent that was infusing at the start of the study drug.	During the first 2 hours of study drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of clinically meaningful hemodynamic abnormality (CMHA) during the maintenance infusion period.		Maintenance infusion period (2 to 24 hours)
Incidence of adverse events (AEs) between the 3 loading-dose paradigms	Adverse events including agitation/anxiety, cardiac dysrhythmias, rebound phenomenon, and signs of withdrawal	Post-dexmedetomidine 24-hour observation period
Incidence of paradoxical hypertension		During the first 2 hours of the post-dexmedetomidine observation period
Incidence of paradoxical hypertension		Post-dexmedetomidine 24-hour observation period
Amount of analgesics administered		2 hours prior, and for the first 2 hours during, study drug administration
Amount of sedatives administered		2 hours prior, and for the first 2 hours during, study drug administration

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: July 21, 2010
• First Submitted That Met QC Criteria: July 22, 2010
• First Posted (Estimate): July 26, 2010

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: Initially intubated; Mechanically ventilated; Post-surgical
• Additional Relevant MeSH Terms: 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-10-03

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No