Anesthesia
Conditions
Brief summary
The purpose of this study is investigate the relationship between BIS™ and propofol with/without remifentanil across a wide range of hypnotic states.
Detailed description
This is a single-center, prospective, non-randomized, cross-over study to collect data to evaluate the relationship between BIS™ and anesthetic regimens. The subjects will receive two regimens of anesthesia with different drug combinations, with at least a 1-week washout period between regimens. Subjects will be sequentially assigned to start with either Propofol (P) or Propofol with 4 ng/ml of Remifentanil (R) regimens while BIS™ bilateral sensor placed on the subject's forehead. The Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale, refer to Appendix A, will be used to measure the level of alertness in sedated subjects with Tetanic Electrical Stimulation (TES) being used once subjects reach a MOAA/S score \<2.
Interventions
DEVICEBIS
Subjects will be sequentially assigned to the propofol or propofol and remifentanil group. The purpose is to capture the BIS value in association with these anesthetics.
Sponsors
Medtronic - MITG
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Intervention model description
The subjects will receive two regimens of anesthesia with different drug combinations, with at least a 1-week washout period between regimens. Subjects will be sequentially assigned to start with either propofol or propofol with remifentanil regiments.
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy (ASA physical status 1), male or female subjects between the ages of 18 to 60 years; 2. Completion of a health screening for a medical history by a licensed physician, nurse practitioner or physician assistant; 3. Vital signs must be within the following ranges to be included: Vital signs measured sitting after 3 minutes rest; heart rate: 45-90 bpm; systolic blood pressure: 110-140; diastolic blood pressure: 50-90. Out-of-range vital signs may be repeated once. \[Pre-dose vital signs will be assessed by the Principal Investigator or designee (e.g., a medically qualified sub-investigator) before study drug administration. The Principal Investigator or designee will verify the eligibility of each subject before dosing\];
Exclusion criteria
1. Has severe contact allergies that may cause a reaction to standard adhesive materials found in pulse oximetry sensors, ECG electrodes, respiration monitor electrodes, or other medical sensors \[self-reported\]; 2. Known neurological disorder (e.g., epilepsy, the presence of a brain tumor, a history of brain surgery, hydrocephalic disorders, depression needing treatment with anti-depressive drugs, a history of brain trauma) \[self-reported and assessment by PI or delegate\]; 3. Known cardiovascular disease (e.g., hypertension, coronary artery disease, prior acute myocardial infarction, any valvular and/or myocardial disease involving a decrease in ejection fraction, arrhythmias, which are either symptomatic or require continuous medication/ pacemaker/ automatic internal cardioverter defibrillator), current implanted pacemaker or automatic internal cardioverter defibrillator \[self-reported and assessment by PI or delegate\]; 4. Has a clinically significant abnormal finding on medical history, physical examination, clinical laboratory tests, or ECG at the screening \[self-reported and assessment by PI or delegate\]; 5. Recent use of psychoactive medication (e.g., benzodiazepines, antiepileptic drugs, ADHD medication, Parkinson's medication, anti-depressant drugs, opioids) \[self-reported and assessment by PI or delegate\]; 6. Subjects with known gastric diseases \[self-reported and assessment by PI or delegate\]; 7. Has a positive urine cotinine test or urine drug screen or oral ethanol test \[POC testing\]; 8. Known history of allergic or adverse response to drugs to be administered \[self-reported\]; 9. Known history of complications relating to previous general anesthesia or conscious sedation \[self-reported and assessment by PI or delegate\]; 10. Known history of malignant hyperthermia \[self-reported and assessment by PI or delegate\]; 11. Has a room air saturation less than 95% by pulse oximetry \[measurement by PI or delegate\]; 12. Has a clinically significant abnormal ECG \[assessment by PI or delegate\]; 13. Has a clinically significant abnormal pulmonary function test via spirometry \[assessment by PI or delegate\]; 14. Pregnant or lactating women \[assessed by urine test and self-reported\]; 15. Subjects with tattooed skin specific to the sensor placement areas (forehead, fingers, chest) \[self-reported and assessment by PI or delegate\]; 16. The subject must not take any prescription medication, except female hormonal contraceptives or hormone replacement therapy, from 146 days before the dosing until the end-of-study visit without evaluation and approval by the Investigator. Subjects who participated in a previous clinical trial who received a required FDA approved concomitant medication, for example, naltrexone, but were not randomized may be considered for participation in this study if they meet the washout requirement \[assessment by PI or delegate\];
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| BIS50 | 4 hours | To determine BIS50 (BIS™ value at which 50% of patients will be unresponsive at given drug concentrations) and other dose-response parameters. BIS™ is a scale 0-100 with values near 100 represent an awake clinical state while 0 denotes the maximal EEG effect possible (i.e., an isoelectric EEG). Responsiveness is measured using the Modified Observer's Assessment of Alertness/ Sedation (MOAA/S). Below a MOAA/S of 2, responsiveness is measured with Tetanic Electrical Stimulation (TES). The subject will receive one stimulation of 50mA, 50 Hz for 5 seconds. Their response, such as withdrawal of the extremity, a facial grimace, or a verbal groan will be recorded. Approximately 2 minutes after this assessment, the BIS™ value will be recorded. When the subject does not respond to the TES stimulation, they will be considered unresponsive and that BIS™ value will be used to determine the BIS50. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| BIS95 | 4 hours | To determine BIS95 (BIS™ value at which 95% of patients will be unresponsive at given drug concentrations) and other dose-response parameters. BIS™ is a scale 0-100 with values near 100 represent an awake clinical state while 0 denotes the maximal EEG effect possible (i.e., an isoelectric EEG). Responsiveness is measured using the Modified Observer's Assessment of Alertness/Sedation (MOAA/S). Below a MOAA/S of 2, responsiveness is measured with Tetanic Electrical Stimulation (TES). The subject will receive one stimulation of 50mA, 50 Hz for 5 seconds. Their response, such as withdrawal of the extremity, a facial grimace, or a verbal groan will be recorded. Approximately 2 minutes after this assessment, the BIS™ value will be recorded. When the subject does not respond to the TES stimulation, they will be considered unresponsive and that BIS™ value will be used to determine the BIS95. |
Countries
United States
Participant flow
Recruitment details
This study recruited healthy, non-smoking (or has refrained from smoking for 2 days) subjects, 18 to 60 years of age. The subjects were distributed across both sexes as equally as practical.
Pre-assignment details
During the study, 34 subjects were consented. 6 subjects were inclusion / exclusion criteria screen failures after consent leaving 28 enrolled subjects. Of these 28 enrolled subjects, 4 subjects were withdrawn due to safety events leaving 24 subjects to be assigned to randomization arms.
Participants by arm
| Arm | Count |
|---|---|
| Randomized Study Participants Baseline measures are reported for subjects who were enrolled and randomized to Propofol first or First Propofol with Remifentanil arms (n=24). Baseline measurements are not reported for subjects who were screen failures (n=6) or withdrawn due to safety events (n=4). | 24 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Cross Over Phase | Physician Decision | 1 | 0 |
| Cross Over Phase | Withdrawal by Subject | 0 | 1 |
| First Phase | Missing data | 1 | 0 |
| First Phase | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | Randomized Study Participants |
|---|---|
| Age, Continuous | 28.5 years STANDARD_DEVIATION 7.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 9 Participants |
| Region of Enrollment United States | 24 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 15 Participants |
| Skin Pigmentation Dark Olive | 3 participants |
| Skin Pigmentation Extremely Dark | 10 participants |
| Skin Pigmentation Olive Hue | 4 participants |
| Skin Pigmentation Very Light | 7 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 10 | 0 / 14 | 0 / 10 |
| other Total, other adverse events | 0 / 14 | 3 / 10 | 8 / 14 | 0 / 10 |
| serious Total, serious adverse events | 0 / 14 | 0 / 10 | 0 / 14 | 0 / 10 |
Outcome results
Primary
BIS50
To determine BIS50 (BIS™ value at which 50% of patients will be unresponsive at given drug concentrations) and other dose-response parameters. BIS™ is a scale 0-100 with values near 100 represent an awake clinical state while 0 denotes the maximal EEG effect possible (i.e., an isoelectric EEG). Responsiveness is measured using the Modified Observer's Assessment of Alertness/ Sedation (MOAA/S). Below a MOAA/S of 2, responsiveness is measured with Tetanic Electrical Stimulation (TES). The subject will receive one stimulation of 50mA, 50 Hz for 5 seconds. Their response, such as withdrawal of the extremity, a facial grimace, or a verbal groan will be recorded. Approximately 2 minutes after this assessment, the BIS™ value will be recorded. When the subject does not respond to the TES stimulation, they will be considered unresponsive and that BIS™ value will be used to determine the BIS50.
Time frame: 4 hours
Population: Intention to Treat (ITT)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Propofol | BIS50 | 60.4 BIS50 Index Score |
| Propofol With Remifentanil | BIS50 | 71.6 BIS50 Index Score |
Secondary
BIS95
To determine BIS95 (BIS™ value at which 95% of patients will be unresponsive at given drug concentrations) and other dose-response parameters. BIS™ is a scale 0-100 with values near 100 represent an awake clinical state while 0 denotes the maximal EEG effect possible (i.e., an isoelectric EEG). Responsiveness is measured using the Modified Observer's Assessment of Alertness/Sedation (MOAA/S). Below a MOAA/S of 2, responsiveness is measured with Tetanic Electrical Stimulation (TES). The subject will receive one stimulation of 50mA, 50 Hz for 5 seconds. Their response, such as withdrawal of the extremity, a facial grimace, or a verbal groan will be recorded. Approximately 2 minutes after this assessment, the BIS™ value will be recorded. When the subject does not respond to the TES stimulation, they will be considered unresponsive and that BIS™ value will be used to determine the BIS95.
Time frame: 4 hours
Population: Intention to Treat (ITT)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Propofol | BIS95 | 47.7 BIS95 index score |
| Propofol With Remifentanil | BIS95 | 63.1 BIS95 index score |