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

Study Overview
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Brief Summary
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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.

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

Conditions
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Intensive Care Unit

Intervention / Treatment
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* Drug: Dexmedetomidine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject or the subject's legally authorized representative has voluntarily signed and dated the informed consent document approved by the Research Ethics Board (REB). 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. 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. 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: Subjects <18 years of age. 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. Subjects with a known allergy to dexmedetomidine. Hypotension based on repeat assessments prior to (within 15 minutes) starting study drug defined as Systolic BP <90 mmHg or Diastolic BP <60 mmHg. Pre-existing bradycardia prior (within 15 minutes) to starting study drug defined as HR <50 bpm. 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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group I - No loading dose<br>No loading dose to be administered during the loading-dose paradigms | Drug: Dexmedetomidine<br> <br> |
| Group II - Loading dose over 10 minutes<br>Loading dose dexmedetomidine 1 mcg/kg administered over 10 minutes during the loading-dose paradigms | Drug: Dexmedetomidine<br> <br> |
| Group III - Loading dose over 20 minutes<br>Loading dose dexmedetomidine 1 mcg/kg administered over 20 minutes during the loading-dose paradigms | Drug: Dexmedetomidine<br> <br> |

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Initially intubated, Mechanically ventilated, Post-surgical