Lusedra (Fospropofol Disodium) for Minimal to Moderate Sedation for Regional Anesthesia Block Prior to Orthopedic Surgery

Study Overview
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Brief Summary
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How does Lusedra compare with current standard of care (midazolam) for minimal to moderate sedation for regional anesthesia blocks prior to orthopedic surgery?

Detailed Description
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The study overall is aimed at establishing the superiority of a single intravenous bolus-dose of Lusedra for routine use in preoperative regional blocks that avoids deeper levels of sedation and increased risk of nerve damage in an over-sedated individual. The shorter half-life of Lusedra should also demonstrate a superior recovery profile compared to midazolam when used as a rescue comparator. While this study will only enroll patients undergoing regional blocks prior to orthopedic surgery, the clinical utility and value of the larger initial intravenous dosing for Lusedra may be evident for many different monitored anesthesia care anesthetic management situations requiring rapid and effective onset of effects.

Official Title
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A Prospective Randomized Study to Assess the Efficacy and Safety of Bolus-dose Lusedra (Fospropofol Disodium) 6.5 mg/kg or 10 mg/kg Versus a Placebo (With Midazolam Rescue) for Minimal-to-moderate Sedation in Patients Undergoing Procedural Sedation for Regional Anesthesia Blocks Prior to Orthopedic Surgery

Conditions
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Procedural Sedation, Regional Anesthesia Block, Orthopedic Surgery

Intervention / Treatment
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* Drug: Fospropofol disodium
* Drug: Fospropofol disodium
* Drug: Placebo + Midazolam
* Drug: Fentanyl


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Undergoing elective orthopedic surgery With a regional block prior to surgery Able to consent and complete the assessments and procedures If female, must be surgically sterile, postmenopausal, or not pregnant or lactating and using an acceptable method of birth control for at least 1 month prior to surgery with a negative urine pregnancy test at screening American Society of Anesthesiologists Physical Classification System status category P1 to P4 Exclusion Criteria: History of allergic reaction or hypersensitivity to any anesthetic agent, opioid, or benzodiazepine Fentanyl citrate injection or midazolam hydrocholoride injection contraindicated

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 10 mg/kg Lusedra<br>10 mg/kg Lusedra initial bolus. | Drug: Fospropofol disodium<br>* 10 mg/kg bolus<br>* Other names: Lusedra;Drug: Fentanyl<br>* All patients will receive a single dose of IV fentanyl (approximately 1 μg/kg not to exceed: 50 μg for patients <60 kg; 75 μg for patients ≥90 kg) five minutes prior to the initial dose of sedative.<br>* Other names: Sublimaze;|
| Active Comparator: 6.5 mg/kg Lusedra<br>6.5 mg/kg Lusedra initial bolus. | Drug: Fospropofol disodium<br>* 6.5 mg/kg bolus<br>* Other names: Lusedra;Drug: Fentanyl<br>* All patients will receive a single dose of IV fentanyl (approximately 1 μg/kg not to exceed: 50 μg for patients <60 kg; 75 μg for patients ≥90 kg) five minutes prior to the initial dose of sedative.<br>* Other names: Sublimaze;|
| Active Comparator: Placebo + Midazolam<br>Placebo initial bolus with dose of midazolam based on patient's weight | Drug: Placebo + Midazolam<br>* Placebo bolus plus midazolam. The dose of midazolam will be based on the patient's weight: 1 mg for patients <60 kg; 1.5 mg for patients ≥60 kg to <90 kg; or 2 mg for patients ≥90 kg<br>* Other names: Versed;Drug: Fentanyl<br>* All patients will receive a single dose of IV fentanyl (approximately 1 μg/kg not to exceed: 50 μg for patients <60 kg; 75 μg for patients ≥90 kg) five minutes prior to the initial dose of sedative.<br>* Other names: Sublimaze;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Sedation Within 4 Minutes | Percentage of patients achieving a Modified Observer's Assessment of Alertness/Sedation Scale score less than or equal to 4, and the block procedure initiated, within 4 minutes of the administration of the first bolus of study drug. The Modified Observer's Assessment of Alertness/Sedation Scale ranges from 0 (does not respond to deep stimulus) to 6 (agitated). The score of 4 equals lethargic response to name spoken in normal tone. | approximately 4 minutes after administration of first bolus of study drug | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Procedural sedation, Regional Anesthesia block, Orthopedic surgery, Lusedra, Fospropofol disodium, Midazolam