Orthopedic Surgery, Procedural Sedation, Regional Anesthesia Block
Conditions
Keywords
Procedural sedation, Regional Anesthesia block, Orthopedic surgery, Lusedra, Fospropofol disodium, Midazolam
Brief summary
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
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.
Interventions
10 mg/kg bolus
DRUGPlacebo + Midazolam
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
DRUGFentanyl
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.
Sponsors
Eisai Inc.
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Sedation Within 4 Minutes | approximately 4 minutes after administration of first bolus of study drug | 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. |
Countries
United States
Participant flow
Recruitment details
Patients were recruited from Mayo Clinic, Arizona from March 1 - 11, 2011.
Participants by arm
| Arm | Count |
|---|---|
| 10 mg/kg Lusedra 10 mg/kg Lusedra initial bolus | 6 |
| 6.5 mg/kg Lusedra 6.5 mg/kg Lusedra initial bolus | 2 |
| Placebo + Midazolam Placebo initial bolus with dose of midazolam based on patient's weight | 5 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | 10 mg/kg Lusedra | 6.5 mg/kg Lusedra | Placebo + Midazolam | Total |
|---|---|---|---|---|
| Age Continuous | 73.2 years STANDARD_DEVIATION 7 | 71.5 years STANDARD_DEVIATION 4.3 | 72 years STANDARD_DEVIATION 12 | 72.6 years STANDARD_DEVIATION 8.2 |
| Sex: Female, Male Female | 4 Participants | 0 Participants | 4 Participants | 8 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 1 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 5 | 1 / 2 | 2 / 5 |
| serious Total, serious adverse events | 1 / 5 | 0 / 2 | 0 / 5 |
Outcome results
Primary
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.
Time frame: approximately 4 minutes after administration of first bolus of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 10 mg/kg Lusedra | Percentage of Participants Achieving Sedation Within 4 Minutes | 100 percentage of participants |
| 6.5 mg/kg Lusedra | Percentage of Participants Achieving Sedation Within 4 Minutes | 50 percentage of participants |
| Placebo + Midazolam | Percentage of Participants Achieving Sedation Within 4 Minutes | 40 percentage of participants |