Multi-site Anesthesia Randomized Controlled STudy of End Tidal Control Compared to Conventional Anesthesia Results

Study Overview
=================
Brief Summary
-----------------
This is a clinical, single blind, randomized, prospective research study. The purpose of this pivotal study is to collect and analyze data on the investigational End tidal Control (Et Control) option feature. To demonstrate that End tidal Control (Et Control) performance is non-inferior to conventional anesthesia practice in an adult surgery population by comparing the performance of the Et Control Arm (investigational arm) to the Control Arm (fresh gas mode).

Detailed Description
-----------------
The purpose of this pivotal study is to demonstrate that End tidal Control performance is non-inferior to conventional anesthesia practice in an adult surgery population, and support a marketing application in the U.S. for clearance of this feature.

Official Title
-----------------
Multi-site Anesthesia Randomized Controlled STudy of End Tidal Control (Et Control) Compared to Conventional Anesthesia Results (MASTER-Anesthesia Trial)

Conditions
-----------------
Et Control Performance in Adult Population Surgery

Intervention / Treatment
-----------------
* Device: Et Control Feature
* Device: Conventional Fresh Gas


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female 18 years old or greater. Scheduled to undergo general inhaled anesthesia that can be safely exposed to 100% oxygen for up to 2 minutes during general anesthesia. Expected to have airway secured with laryngeal mask airway (LMA) or endotracheal tube. Undergoing a surgical procedure that is anticipated by the investigator to take greater than or equal to 1 hour (operative time measured from induction to cessation of general inhalation anesthetic). American Society of Anesthesiologists (ASA) status classification system I through III: ASA Physical Status 1 = a normal healthy patient ASA Physical Status 2 = a patient with mild systemic disease ASA Physical Status 3 = a patient with severe systemic disease Undergoing intravenous induction. Ability to provide written informed consent. Exclusion Criteria: Have emergency medical condition requiring surgery. Are female subjects, who are pregnant or lactating. Any subject undergoing cardiac bypass surgery. Any subject undergoing open chest surgery.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Et Control<br>Subjects, meeting the American Society of Anesthesiologists status classification system 1-3, to undergo a surgical procedure with inhaled anesthesia using the investigational Et Control option intervention. For Subjects under the Et Control option, the investigator will use and initiate Et Control after the airway is secured and mechanical ventilation is initiated. Machine log data is collected when the investigator initiates the start of anesthesia case on the Aisys CS2. Adjustments to the anesthesia machine settings, discontinuation of use of the investigational Et Control option, and changes to treatment are based upon clinician judgment for the well being of the subject. | Device: Et Control Feature<br>* Subjects using Et Control option; the investigator will use and initiate Et Control after the airway is secured and mechanical ventilation is initiated. Machine log data is collected when the investigator initiates the start of anesthesia case on the Aisys CS2. Adjustments to the anesthesia machine settings, discontinuation of use of the investigational Et Control option, and changes to treatment are based upon clinician judgment for the wellbeing of the subject. The clinician must continuously monitor measured inspired and end tidal oxygen and anesthetic concentrations to assess individual responses and compare to the target concentrations.<br>|
| Active Comparator: Control Arm<br>Subjects, meeting the American Society of Anesthesiologists status classification system 1-3, to undergo a surgical procedure with inhaled anesthesia using conventional fresh gas intervention. For subjects under the conventional option, the investigator will use their conventional means to adjust the vaporizer and mixer, and monitor the patient gas concentrations with the legally marketed Aisys CS2 anesthesia machine without the investigational Et Control feature. | Device: Conventional Fresh Gas<br>* Subjects to undergo a surgical procedure with inhaled anesthesia meeting the American Society of Anesthesiologists status classification system 1-3. Subjects using conventional option; the investigator will use their conventional means to adjust the vaporizer and mixer, and monitor the patient gas concentrations with the legally marketed Aisys CS2 anesthesia machine without the investigational Et Control feature. Machine log data collection will end, when an end case is confirmed on the Aisys CS2 at the end of the anesthesia case.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Duration Without Large Deviation of End-Tidal Anesthetic Agent (EtAA) Based on Extraction Algorithm (ALG) | Percent duration of EtAA concentration during steady state maintained within the acceptable limit, which is defined as the greater of 5% of the steady state inhaled anesthetic agent concentration and 0.6% v/v for Desflurane (Des), 0.2% v/v for Sevoflurane (Sev), or 0.1% v/v for Isoflurane (Iso). The percent duration is the weighted average of all steady states for a subject, using the duration of steady state as the weight. Steady state concentration is based on an extraction algorithm described in Appendix 2 of the protocol. | Duration of each steady state, an average of approximately 60 minutes | 
| Percent Duration Without Large Deviation of EtAA Based on Clinician's or Investigators' Recorded Target Values of Anesthetic Agent and Oxygen (TGT) | Percent duration of EtAA concentration during steady state maintained within the acceptable limit, which is defined as the greater of 5% of the steady state inhaled anesthetic agent concentration and 0.6% v/v for Desflurane (Des), 0.2% v/v for Sevoflurane (Sev), or 0.1% v/v for Isoflurane (Iso). The percent duration is the weighted average of all steady states for a subject, using the duration of steady state as the weight. Data obtained using the clinicians' or Investigators' recorded target (TGT) values of anesthetic agent and oxygen for the Control Arm and using the set target values for the Et Control Arm. | Duration of each steady state, an average of approximately 60 minutes | 
| Percent Duration Without Large Deviation of End-Tidal Oxygen (EtO2) Based on Extraction Algorithm (ALG) | Percent duration of EtAA concentration during steady state maintained within the acceptable limit, which is defined as the greater of 5% of the steady state inhaled anesthetic agent concentration and 0.6% v/v for Desflurane (Des), 0.2% v/v for Sevoflurane (Sev), or 0.1% v/v for Isoflurane (Iso). The percent duration is the weighted average of all steady states for a subject, using the duration of steady state as the weight. Values based on the extraction algorithm described in Appendix 2 of the protocol (ALG). | Duration of each steady state, an average of approximately 60 minutes | 
| Percent Duration Without Large Deviation of EtO2 Based on Clinician's or Investigators' Recorded Target Values of Anesthetic Agent and Oxygen (TGT) | Percent duration of EtAA concentration during steady state maintained within the acceptable limit, which is defined as the greater of 5% of the steady state inhaled anesthetic agent concentration and 0.6% v/v for Desflurane (Des), 0.2% v/v for Sevoflurane (Sev), or 0.1% v/v for Isoflurane (Iso). The percent duration is the weighted average of all steady states for a subject, using the duration of steady state as the weight. Values based on clinicians' or Investigators' recorded target values (TGT) | Duration of each steady state, an average of approximately 60 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy Response Time EtAA Based on Extraction Algorithm (ALG) | Response time: time to reach 90% of the desired change in EtAA steady state mean concentration. Values based on the extraction algorithm described in Appendix 2 of the protocol (ALG). | Duration of each steady state, an average of approximately 60 minutes | 
| Efficacy: Response Time for EtAA Based on Clinician's or Investigators' Recorded Target Values of Anesthetic Agent and Oxygen (TGT) | time to reach 90% of the desired change in EtAA and EtO2 steady state mean concentration. Values based on clinicians' or Investigators' recorded values (TGT). | Duration of each steady state, an average of approximately 60 minutes | 
| Efficacy Response Time for EtO2 Based on Extraction Algorithm (ALG) | Response time: time to reach 90% of the desired change in EtO2 steady state mean concentration. Values based on the extraction algorithm described in Appendix 2 of the protocol (ALG). | Duration of each steady state, an average of approximately 60 minutes. | 
| Efficacy: Response Time for EtO2 Based on Clinician's or Investigators' Recorded Target Values of Anesthetic Agent and Oxygen (TGT) | Response time: time to reach 90% of the desired change in EtAA and EtO2 steady state mean concentration. Values based on clinicians' or Investigators' recorded values (TGT). | Duration of each steady state, an average of approximately 60 minutes | 
| Efficacy: Settling Time for EtAA Based on the Extraction Algorithm (ALG) | Settling time: time to achieve the desired EtAA steady state mean concentration. Values based on the extraction algorithm described in Appendix 2 of the protocol (ALG). | Duration of each steady state, an average of approximately 60 minutes | 
| Efficacy: Settling Time for EtAA Based on Clinician's or Investigators' Recorded Target Values of Anesthetic Agent and Oxygen (TGT) | Settling time: time to achieve the desired EtAA steady state mean concentration. Values based on clinicians' or Investigators' recorded values (TGT). | Duration of each steady state, an average of approximately 60 minutes | 
| Efficacy: Settling Time for EtO2 Based on the Extraction Algorithm (ALG) | Settling time: time to achieve the desired EtO2 steady state mean concentration. Values based on the extraction algorithm described in Appendix 2 of the protocol (ALG). | Duration of each steady state, an average of approximately 60 minutes | 
| Efficacy: Settling Time for EtO2 Based on Based on Clinician's or Investigators' Recorded Target Values of Anesthetic Agent and Oxygen (TGT) | time to achieve the desired EtO2 steady state mean concentration. Values based on clinicians' or Investigators' recorded values (TGT). | Duration of each steady state, an average of approximately 60 minutes | 
| Efficacy: Overshoot Amount of the Desired EtAA Based on Extraction Algorithm (ALG) | Overshoot amount of the desired EtAA from steady state mean concentration. Command Overshoot is defined as the maximum value beyond the desired end tidal concentration from the start of the step change until the Settling Time. Values based on the extraction algorithm described in Appendix 2 of the protocol (ALG). | Duration of each steady state, an average of approximately 60 minutes | 
| Efficacy: Overshoot Amount of the Desired EtAA Amount Based on Clinician's or Investigators' Recorded Target Values of Anesthetic Agent and Oxygen (TGT) | Overshoot amount of the desired EtAA from steady state mean concentration. Command Overshoot is defined as the maximum value beyond the desired end tidal concentration from the start of the step change until the Settling Time. Values based on clinicians' or Investigators' recorded values (TGT). | Duration of each steady state, an average of approximately 60 minutes | 
| Efficacy: Overshoot Amount of Desired EtO2 Amount Based on the Extraction Algorithm (ALG) | Overshoot amount of the desired EtO2 from steady state mean concentration. Command Overshoot is defined as the maximum value beyond the desired end tidal concentration from the start of the step change until the Settling Time. Values based on the extraction algorithm described in Appendix 2 of the protocol (ALG). | Duration of each steady state, an average of approximately 60 minutes | 
| Efficacy: Overshoot Amount of Desired EtO2 Amount Based on Clinician's or Investigators' Recorded Target Values of Anesthetic Agent and Oxygen (TGT) | Overshoot amount of the desired EtO2 from steady state mean concentration. Command Overshoot is defined as the maximum value beyond the desired end tidal concentration from the start of the step change until the Settling Time. Values based on clinicians' or Investigators' recorded values (TGT). | Duration of each steady state, an average of approximately 60 minutes | 
| Accuracy of Et Control in Maintaining EtAA Control Between User Set Target and Settling End Tidal Concentrations Based on the Extraction Algorithm (ALG) | Accuracy of Et Control in maintaining EtAA control between user set target and settling end tidal concentrations. Calculated for Et Control arm only. The accuracy measures include absolute difference between steady state and set EtAA concentrations. The acceptable limits defined by the primary endpoint were: 0.1% of Isoflurane, 0.2% for Sevoflurane, 0.6% for Desflurane. As a measure of Absolute Difference between Steady State and Set EtAA Concentration (%). Values based on the extraction algorithm described in Appendix 2 of the protocol (ALG). | Duration of surgery, average of 112.1 minutes (+/- 78.7 minutes) | 
| Accuracy of ET Control in Maintaining EtAA Control Between User Set Target and Settling End Tidal Concentrations Based on Clinician's or Investigators' Recorded Target Values of Anesthetic Agent and Oxygen (TGT) | Accuracy of ET Control in maintatining EtAA between user set target and settling end tidal concentrations. Calculated for ET Control arm only. The accuracy measures include absolute difference between steady state and set EtAA concentrations. The acceptable limits defined by the primary endpoint were: 0.1% of Isoflurane, 0.2% for Sevoflurane, 0.6% for Desflurane. Values based on clinicians' or Investigators' recorded values (TGT). | Duration of Surgery | 
| Accuracy of Et Control in Maintaining EtO2 Between User Set Target and Settling End Tidal Concentrations Based on the Extraction Algorithm (ALG) | Accuracy of Et Control in maintaining EtO2 control between user set target and settling end tidal concentrations. Calculated for Et Control arm only. outcome measures the absolute difference between Steady State and Set EtO2 Concentrations. The acceptable limit defined by the primary endpoint was < 5% v/v. Values based on the extraction algorithm described in Appendix 2 of the protocol (ALG). | Duration of surgery, average of 112.1 minutes (+/- 78.7 minutes) | 
| Accuracy of Et Control in Maintaining EtO2 Between User Set Target and Settling End Tidal Concentrations Based on Clinician's or Investigators' Recorded Target Values of Anesthetic Agent and Oxygen (TGT) | Accuracy of Et Control in maintaining EtO2 control between user set target and settling end tidal concentrations. Calculated for Et Control arm only. outcome measures the absolute difference between Steady State and Set EtO2 Concentrations. The acceptable limit defined by the primary endpoint was < 5% v/v. Values based on clinicians' or Investigators' recorded values (TGT). | Duration of surgery, average of 112.1 minutes (+/- 78.7 minutes) |