Propofol and Etomidate Admixtures Comparisons Trial (PEAC Trial)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the hemodynamics and adverse event profile in comparison between two treatment arms, one using an admixture of propofol and etomidate at a ratio by volume of 25%/75% (P2E7), and one using an admixture of propofol and etomidate at a ratio by volume of 75%/25% (P7E2), for anesthesia during endoscopic procedures at the Clements University Hospital (CUH) endoscopy lab (Endo).

Detailed Description
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Procedural/Surgical anesthesia induction, administration and maintenance with propofol combined with etomidate is commonly used in routine clinical practice in patient with compromised cardiopulmonary status. However, there is no definitive trend or understanding from the literature to discern which ratio of admixture is appropriate for providing stable hemodynamics and minimizing side effects for procedural sedation in gastrointestinal endoscopy procedures. Given the increasing volume for gastrointestinal endoscopy, the increasingly older and greater chronic disease burden of the endoscopic patient population, and the increased utilization of anesthesia for endoscopic procedures this clinical trial aims to provide timely, meaningful and impactful guidance and information for the safe conductance of anesthesia in this patient population. The objectives are to compare the treatment arms, P2E7 and P7E2, in a randomized controlled double-blind trial for anesthesia for endoscopic procedures. Comparison between an admixture of Propofol/Etomidate 75%/25% versus 25%/75% being utilized as principal anesthetic for endoscopic procedures at CUH endoscopy lab. Propofol and etomidate can be mixed together in a syringe or similar container for up to 24 hours without adversely affecting appearance, pH, particle size and distribution, zeta potential, observation under centrifugation and drug content and impurity demonstrating the mixture to be physically and chemically compatible. Propofol and Etomidate are both FDA approved for induction and maintenance of general anesthesia in adult patients. Propofol and Etomidate in a wide ranging ratio of combinations in admixture have been utilized for general anesthesia induction and maintenance both in regular standard of care daily clinical practice and within a profound number of research trials including up to a ratio of 80% etomidate and 20 % propofol by volume. Therefore the clinical practice of etomidate and propofol in admixture for the induction and maintenance of general anesthesia in adult patients is standard of care and well founded in the anesthesiology literature. However, there are several important questions about which potential ratio of both drugs provides the best combination of favorable cardiopulmonary effects while having an acceptably low incidence of adverse effects. Thus, this current proposed trial is intended to answer several important questions on that matter. This trial also will have actual blinding of both patients and practitioners at time of drug administration. Propofol is a white liquid and etomidate is a clear liquid. Thus, past trials where either pure drug was given in sequence or at the same time by separate syringes could not have had any blinding because of this obvious physical quality of the medications. Therefore, only a trial involving an admixture of varying ratios of both drugs could possibly hope to achieve actual blinding as is required for rigorous analysis of results without introducing the bias that comes from a lack of true blinding of patients and practitioners.

Official Title
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Propofol and Etomidate Admixtures Comparisons Trial (PEAC Trial)

Conditions
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Anesthesia, Propofol Adverse Reaction, Etomidate Adverse Reaction, Anesthesia Complication, Anesthesia; Adverse Effect, Anesthesia; Reaction

Intervention / Treatment
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* Drug: Admixture of propofol and etomidate at a ratio by volume of 75%/25% (P7E2)
* Drug: Admixture of propofol and etomidate at a ratio by volume of 25%/75% (P2E7)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients (age ≥18 years old) Having endoscopic procedure at CUH with anesthesia ASA 3 or above Ejection Fraction test result available Exclusion Criteria: Known allergies or adverse reactions to study drugs or study drug components or preservatives Patient refusal Clinician refusal Documented cognitive impairments precluding subject ability to consent for themselves unless a surrogate documented legally acceptable decision maker consents for patient participation Prisoner or incarcerated or patients held by law enforcement officials in custody Pregnancy or patient refusal for pregnancy testing or screening (standard UTSW policy and protocol requires pregnancy testing for appropriate patients prior to anesthesia)

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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This a prospective double blind randomized controlled clinical trial. The purpose of this study is to evaluate the hemodynamics and adverse event profile in comparison between two treatment arms, one using an admixture of propofol and etomidate at a ratio by volume of 25%/75% (P2E7), and one using an admixture of propofol and etomidate at a ratio by volume of 75%/25% (P7E2), for anesthesia during endoscopic procedures at the Clements University Hospital endoscopy lab.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Admixture of propofol and etomidate at a ratio by volume of 75%/25% (P7E2)<br>This a prospective double blind randomized controlled clinical trial. The purpose of this study is to evaluate the hemodynamics and adverse event profile in comparison between two treatment arms, one using an admixture of propofol and etomidate at a ratio by volume of 25%/75% (P2E7), and one using an admixture of propofol and etomidate at a ratio by volume of 75%/25% (P7E2), for anesthesia during endoscopic procedures at the Clements University Hospital endoscopy lab. | Drug: Admixture of propofol and etomidate at a ratio by volume of 75%/25% (P7E2)<br>* The purpose of this study is to evaluate the hemodynamics and adverse event profile in comparison between two treatment arms, one using an admixture of propofol and etomidate at a ratio by volume of 25%/75% (P2E7), and one using an admixture of propofol and etomidate at a ratio by volume of 75%/25% (P7E2), for anesthesia during endoscopic procedures at the Clements University Hospital (CUH) endoscopy lab (Endo). The objectives are to compare the treatment arms, P2E7 and P7E2, in a randomized controlled double-blind trial for anesthesia for endoscopic procedures. Comparison between an admixture of Propofol/Etomidate 75%/25% versus 25%/75% being utilized as principal anesthetic for endoscopic procedures at CUH endoscopy lab.<br>* Other names: etomidate 25% by volume;|
| Experimental: Admixture of propofol and etomidate at a ratio by volume of 25%/75% (P2E7)<br>This a prospective double blind randomized controlled clinical trial. The purpose of this study is to evaluate the hemodynamics and adverse event profile in comparison between two treatment arms, one using an admixture of propofol and etomidate at a ratio by volume of 25%/75% (P2E7), and one using an admixture of propofol and etomidate at a ratio by volume of 75%/25% (P7E2), for anesthesia during endoscopic procedures at the Clements University Hospital endoscopy lab. | Drug: Admixture of propofol and etomidate at a ratio by volume of 25%/75% (P2E7)<br>* The purpose of this study is to evaluate the hemodynamics and adverse event profile in comparison between two treatment arms, one using an admixture of propofol and etomidate at a ratio by volume of 25%/75% (P2E7), and one using an admixture of propofol and etomidate at a ratio by volume of 75%/25% (P7E2), for anesthesia during endoscopic procedures at the Clements University Hospital (CUH) endoscopy lab (Endo). The objectives are to compare the treatment arms, P2E7 and P7E2, in a randomized controlled double-blind trial for anesthesia for endoscopic procedures. Comparison between an admixture of Propofol/Etomidate 75%/25% versus 25%/75% being utilized as principal anesthetic for endoscopic procedures at CUH endoscopy lab.<br>* Other names: etomidate 75% by volume;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time weighted average mean arterial pressure within treatment arm | Time weighted average mean arterial pressure (every 15 minutes calculate average mean arterial pressure for that interval, then end of case calculate mean of all those means for the entire case) | Throughout entire study estimated to take 6 to 12 months to complete | 
| Average within treatment arm vasopressor use by number of units | Vasopressor use by number of units (1 unit of vasopressor being defined as 1 unit vasopressor = 100 mcg phenylephrine = 5 mg ephedrine = 0.5 units vasopressin = 5 mcg norepinephrine)4-9 throughout entire intraoperative period (subjects on vasopressor infusions on arrival for endoscopy will not have those vasopressor units added in UNLESS during case, anesthesia clinicians adjust the infusion based on intraoperative clinical situation as well as all bolus doses and new infusions being added as with all other subjects) | Throughout entire study estimated to take 6 to 12 months to complete | 
| Average within treatment arm total minutes under 92% oxygen saturation | Average within treatment arm total minutes under 92% oxygen saturation by pulse oximetry during entire case | Throughout entire study estimated to take 6 to 12 months to complete | 
| % of cases with any MAP below 50 | % of cases with any MAP below 50 | Throughout entire study estimated to take 6 to 12 months to complete | 
| % of cases with any MAP >60% below patient's immediate preoperative MAP | % of cases with any MAP >60% below patient's immediate preoperative MAP | Throughout entire study estimated to take 6 to 12 months to complete | 
| % of cases with any treatment for Post Operative Nausea and Vomiting | % of cases with any treatment for Post Operative Nausea and Vomiting | Throughout entire study estimated to take 6 to 12 months to complete | 
| % of cases with any oxygen saturation event below 85% by pulse oximetry | % of cases with any oxygen saturation event below 85% by pulse oximetry | Throughout entire study estimated to take 6 to 12 months to complete | 
| % of cases with any rapid response or code blue event within 24 hours from anesthesia start | % of cases with any rapid response or code blue event within 24 hours from anesthesia start | Throughout entire study estimated to take 6 to 12 months to complete | 
| Within treatment arm % of total group with a composite MACE event in the 30 days | Within treatment arm % of total group with a composite MACE event in the 30 days after starting on day of drug administration | Throughout entire study estimated to take 6 to 12 months to complete | 
| Within treatment arm % of total group with a classic MACE event in the 30 days | Within treatment arm % of total group with a classic MACE event in the 30 days after starting on day of drug administration | Throughout entire study estimated to take 6 to 12 months to complete | 
| Average within treatment arm antiemetic use by number of doses | Average within treatment arm antiemetic use by number of doses irrespective of antiemetic drug choice | Throughout entire study estimated to take 6 to 12 months to complete | 
| Average within treatment arm time in minutes after dressing complete to discharge | Average within treatment arm time in minutes after dressing complete to discharge to next phase of care or to home from immediate recovery phase of care | Throughout entire study estimated to take 6 to 12 months to complete | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Within each treatment arm, average of anesthesia clinicians' assessment of quality | Within each treatment arm, average of anesthesia clinicians' assessment of quality of anesthesia during case: Poor, Below Average, Average, Above Average, Excellent (0,1,2,3,4) from all anesthesia staff then average for each treatment arm | Throughout entire study estimated to take 6 to 12 months to complete | 
| Within each treatment arm, average of endoscopists' assessment of quality | Within each treatment arm, average of endoscopists' assessment of quality of anesthesia during case: Poor, Below Average, Average, Above Average, Excellent (0,1,2,3,4) from all endoscopy staff then average for each treatment arm | Throughout entire study estimated to take 6 to 12 months to complete | 
| Within each treatment arm, average of patients' assessment of quality | Within each treatment arm, average of patients' assessment of quality of anesthesia during case: Poor, Below Average, Average, Above Average, Excellent (0,1,2,3,4) from all patients then average for each treatment arm | Throughout entire study estimated to take 6 to 12 months to complete | 
| Within each treatment arm, number of events of any use of 2 or more | Within each treatment arm, number of events of any use of 2 or more different (beyond study admixtures) sedative or anesthetic adjunct medications | Throughout entire study estimated to take 6 to 12 months to complete | 
| Within each treatment arm, number of events of any use of two or more | Within each treatment arm, number of events of any use of two or more types of antiemetic drugs | Throughout entire study estimated to take 6 to 12 months to complete | 
| Average time in immediate recovery area before discharge to next phase of care | Average time in immediate recovery area before discharge to next phase of care or to home | Throughout entire study estimated to take 6 to 12 months to complete | 
| Average time from dressing complete to modified Aldrete score >8 | Average time from dressing complete to modified Aldrete score >8 | Throughout entire study estimated to take 6 to 12 months to complete | 
| Within each treatment arm number of composite MACE events in the 30 days | Within each treatment arm number of composite MACE events in the 30 days after starting on day of drug administration | Throughout entire study estimated to take 6 to 12 months to complete | 
| Within each treatment arm number of classic MACE events in the 30 days | Within each treatment arm number of classic MACE events in the 30 days after starting on day of drug administration | Throughout entire study estimated to take 6 to 12 months to complete | 
| Average within treatment arm total dose (mL) of admixture administered | Average within treatment arm total dose (mL) of admixture administered during entire case divided by average time from induction to dressing complete (minutes) | Throughout entire study estimated to take 6 to 12 months to complete | 
| Average within treatment arm total dose (mg) of etomidate during entire case | Average within treatment arm total dose (mg) of etomidate during entire case divided by average time from induction to dressing complete (minutes) | Throughout entire study estimated to take 6 to 12 months to complete | 
| Average within treatment arm total dose (mg) of propofol during entire case | Average within treatment arm total dose (mg) of propofol during entire case divided by average time from induction to dressing complete (minutes) | Throughout entire study estimated to take 6 to 12 months to complete | 
| Average within treatment arm total dose of adjunct sedatives | Average within treatment arm total dose of fentanyl, sufentanil, midazolam, diphenhydramine, ketamine, morphine, hydromorphone, dexmedetomidine, undiluted propofol, undiluted etomidate (either in mcg or mg as appropriate for each drug) divided by average time from induction to dressing complete (minutes) | Throughout entire study estimated to take 6 to 12 months to complete | 
| Within each treatment arm, number of events of any episode of vomiting | Within each treatment arm, number of events of any episode of vomiting | Throughout entire study estimated to take 6 to 12 months to complete | 
| Within each treatment arm, number of events of any complaint of nausea | Within each treatment arm, number of events of any complaint of nausea | Throughout entire study estimated to take 6 to 12 months to complete | 
| Within each treatment arm, number of events of any syncopal event | Within each treatment arm, number of events of any syncopal event | Throughout entire study estimated to take 6 to 12 months to complete | 
| Within each treatment arm, number of events of any use of one type of antiemetic drug | Within each treatment arm, number of events of any use of one type of antiemetic drug | Throughout entire study estimated to take 6 to 12 months to complete | 
| Within each treatment arm, number of events of any unanticipated admission | Within each treatment arm, number of events of any unanticipated admission, or transfer to higher level of care in the 24 hours after starting on day of drug administration | Throughout entire study estimated to take 6 to 12 months to complete | 
| Within each treatment arm, number of events of any airway adjunct usage | Within each treatment arm, number of events of any airway adjunct usage (oral airway, nasal airway, need for intermittent mask ventilation) | Throughout entire study estimated to take 6 to 12 months to complete | 
| Within each treatment arm, number of events of any use of any additional sedatives | Within each treatment arm, number of events of any use of any additional sedative or anesthetic adjunct medication (beyond study admixtures) during case (fentanyl, sufentanil, midazolam, diphenhydramine, ketamine, morphine, hydromorphone, dexmedetomidine, undiluted propofol, undiluted etomidate) | Throughout entire study estimated to take 6 to 12 months to complete | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sedation, anesthesia, anesthesiology, adverse drug reaction, drug side effect, cardiopulmonary, hemodynamics