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

• ClinicalTrials.gov Identifier: NCT05358535
• Recruitment Status: Recruiting
• First Posted: May 3, 2022
• Last Update Posted: November 1, 2022
• Sponsor: University of Texas Southwestern Medical Center
• Information provided by (Responsible Party): Joseph Hendrix, University of Texas Southwestern Medical Center

Tracking Information

• First Submitted Date: April 21, 2022
• First Posted Date: May 3, 2022
• Last Update Posted Date: November 1, 2022
• Actual Study Start Date: September 19, 2022
• Estimated Primary Completion Date: December 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 2, 2022)

• Time weighted average mean arterial pressure within treatment arm [ Time Frame: Throughout entire study estimated to take 6 to 12 months to complete ]
  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)
• Average within treatment arm vasopressor use by number of units [ Time Frame: Throughout entire study estimated to take 6 to 12 months to complete ]
  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)
• Average within treatment arm total minutes under 92% oxygen saturation [ Time Frame: Throughout entire study estimated to take 6 to 12 months to complete ]
  Average within treatment arm total minutes under 92% oxygen saturation by pulse oximetry during entire case
• % of cases with any MAP below 50 [ Time Frame: Throughout entire study estimated to take 6 to 12 months to complete ]
  % of cases with any MAP below 50
• % of cases with any MAP >60% below patient's immediate preoperative MAP [ Time Frame: 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 treatment for Post Operative Nausea and Vomiting [ Time Frame: 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 oxygen saturation event below 85% by pulse oximetry [ Time Frame: 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 rapid response or code blue event within 24 hours from anesthesia start [ Time Frame: 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
• Within treatment arm % of total group with a composite MACE event in the 30 days [ Time Frame: 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 after starting on day of drug administration
• Within treatment arm % of total group with a classic MACE event in the 30 days [ Time Frame: 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 after starting on day of drug administration
• Average within treatment arm antiemetic use by number of doses [ Time Frame: Throughout entire study estimated to take 6 to 12 months to complete ]
  Average within treatment arm antiemetic use by number of doses irrespective of antiemetic drug choice
• Average within treatment arm time in minutes after dressing complete to discharge [ Time Frame: Throughout entire study estimated to take 6 to 12 months to complete ]
  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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 2, 2022)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Propofol and Etomidate Admixtures Comparisons Trial (PEAC Trial)
• Official Title: Propofol and Etomidate Admixtures Comparisons Trial (PEAC Trial)
• Brief Summary: 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

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.

• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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 (Participant, Care Provider)
Masking Description:

Blinding plan: Either the investigational drug service with the CUH central pharmacy will prepare the admixture syringes or a separate anesthesia staff not involved in subject's case will prepare admixture syringes thus preventing any case personnel involved with subject's case or subject from knowing which admixture is present within syringes for subject's case.

Primary Purpose: Treatment

Condition

• Anesthesia
• Propofol Adverse Reaction
• Etomidate Adverse Reaction
• Anesthesia Complication
• Anesthesia; Adverse Effect
• Anesthesia; Reaction

Intervention

• Drug: Admixture of propofol and etomidate at a ratio by volume of 75%/25% (P7E2)

  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.

  Other Names:

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

  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.

  Other Names:

  • propofol
  • etomidate
  • P2E7
  • propofol 25% by volume
  • etomidate 75% by volume

Study Arms

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

Publications *

• Chen L, Liang X, Tan X, Wen H, Jiang J, Li Y. Safety and efficacy of combined use of propofol and etomidate for sedation during gastroscopy: Systematic review and meta-analysis. Medicine (Baltimore). 2019 May;98(20):e15712. doi: 10.1097/MD.0000000000015712.
• Yoon SW, Choi GJ, Lee OH, Yoon IJ, Kang H, Baek CW, Jung YH, Woo YC. Comparison of propofol monotherapy and propofol combination therapy for sedation during gastrointestinal endoscopy: A systematic review and meta-analysis. Dig Endosc. 2018 Sep;30(5):580-591. doi: 10.1111/den.13050. Epub 2018 Apr 17.
• Hao L, Hu X, Zhu B, Li W, Huang X, Kang F. Clinical observation of the combined use of propofol and etomidate in painless gastroscopy. Medicine (Baltimore). 2020 Nov 6;99(45):e23061. doi: 10.1097/MD.0000000000023061.
• Goradia S, Sardaneh AA, Narayan SW, Penm J, Patanwala AE. Vasopressor dose equivalence: A scoping review and suggested formula. J Crit Care. 2021 Feb;61:233-240. doi: 10.1016/j.jcrc.2020.11.002. Epub 2020 Nov 14.
• Saravanan S, Kocarev M, Wilson RC, Watkins E, Columb MO, Lyons G. Equivalent dose of ephedrine and phenylephrine in the prevention of post-spinal hypotension in Caesarean section. Br J Anaesth. 2006 Jan;96(1):95-9. doi: 10.1093/bja/aei265. Epub 2005 Nov 25.
• French WB, Rothstein WB, Scott MJ. Time to Use Peripheral Norepinephrine in the Operating Room. Anesth Analg. 2021 Jul 1;133(1):284-288. doi: 10.1213/ANE.0000000000005558. No abstract available. Erratum In: Anesth Analg. 2021 Nov 1;133(5):e62.
• Mohta M, Dubey M, Malhotra RK, Tyagi A. Comparison of the potency of phenylephrine and norepinephrine bolus doses used to treat post-spinal hypotension during elective caesarean section. Int J Obstet Anesth. 2019 May;38:25-31. doi: 10.1016/j.ijoa.2018.12.002. Epub 2018 Dec 13.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 21, 2022): 200
• Original Estimated Enrollment (submitted: May 2, 2022): 150
• Estimated Study Completion Date: June 2024
• Estimated Primary Completion Date: December 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Adult patients (age ≥18 years old)
2. Having endoscopic procedure at CUH with anesthesia
3. ASA 3 or above
4. Ejection Fraction test result available

Exclusion Criteria:

1. Known allergies or adverse reactions to study drugs or study drug components or preservatives
2. Patient refusal
3. Clinician refusal
4. Documented cognitive impairments precluding subject ability to consent for themselves unless a surrogate documented legally acceptable decision maker consents for patient participation
5. Prisoner or incarcerated or patients held by law enforcement officials in custody
6. Pregnancy or patient refusal for pregnancy testing or screening (standard UTSW policy and protocol requires pregnancy testing for appropriate patients prior to anesthesia)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Joseph Hendrix; 2146486400; joseph.hendrix@utsouthwestern.edu

Contact: Christopher Choi; 2146486400; christopher.choi@utsouthwestern.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05358535
• Other Study ID Numbers: STU-TBD
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: Yes

Plan Description

1. PHI (name, date of birth, Medical Record number, phone number, email account, admission date)
2. Demographics (Age, height, weight, BMI)
3. Medical history

4. Medication list Intraoperative data collection

   • 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) Area Under the Threshold for mean arterial pressure (both predefined threshold of 65 mm Hg and for 40% below patient's immediate preoperative MAP)
   • 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)

• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Supporting Materials: Analytic Code
• Time Frame: At conclusion of all data analysis and available permanently
• Access Criteria: Only study personnel

• Current Responsible Party: Joseph Hendrix, University of Texas Southwestern Medical Center
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Texas Southwestern Medical Center
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Kapil Anand; University of Texas

• PRS Account: University of Texas Southwestern Medical Center
• Verification Date: October 2022