Clinical trial NCT05358535: Propofol and Etomidate Admixtures Comparisons Trial (PEAC Trial)
Official title: Propofol and Etomidate Admixtures Comparisons Trial (PEAC Trial)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Anesthesia
Propofol Adverse Reaction
Etomidate Adverse Reaction
Anesthesia Complication
Anesthesia; Adverse Effect
Anesthesia; Reaction
Keywords: anesthesia
anesthesiology
adverse drug reaction
drug side effect
sedation
cardiopulmonary
hemodynamics
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
First posted: 2022-05-03
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Time weighted average mean arterial pressure within treatment arm
timeFrame: Throughout entire study estimated to take 6 to 12 months to complete
measure: Average within treatment arm vasopressor use by number of units
timeFrame: Throughout entire study estimated to take 6 to 12 months to complete
measure: Average within treatment arm total minutes under 92% oxygen saturation
timeFrame: Throughout entire study estimated to take 6 to 12 months to complete
measure: % of cases with any MAP below 50
timeFrame: Throughout entire study estimated to take 6 to 12 months to complete
measure: % of cases with any MAP >60% below patient's immediate preoperative MAP
timeFrame: Throughout entire study estimated to take 6 to 12 months to complete
measure: % of cases with any treatment for Post Operative Nausea and Vomiting
timeFrame: Throughout entire study estimated to take 6 to 12 months to complete
measure: % of cases with any oxygen saturation event below 85% by pulse oximetry
timeFrame: Throughout entire study estimated to take 6 to 12 months to complete
measure: % of cases with any rapid response or code blue event within 24 hours from anesthesia start
timeFrame: Throughout entire study estimated to take 6 to 12 months to complete
measure: Within treatment arm % of total group with a composite MACE event in the 30 days
timeFrame: Throughout entire study estimated to take 6 to 12 months to complete
measure: Within treatment arm % of total group with a classic MACE event in the 30 days
timeFrame: Throughout entire study estimated to take 6 to 12 months to complete
measure: Average within treatment arm antiemetic use by number of doses
timeFrame: Throughout entire study estimated to take 6 to 12 months to complete
measure: Average within treatment arm time in minutes after dressing complete to discharge
timeFrame: Throughout entire study estimated to take 6 to 12 months to complete
Secondary outcomes:
measure: Within each treatment arm, average of anesthesia clinicians' assessment of quality
timeFrame: Throughout entire study estimated to take 6 to 12 months to complete
measure: Within each treatment arm, average of endoscopists' assessment of quality
timeFrame: Throughout entire study estimated to take 6 to 12 months to complete
measure: Within each treatment arm, average of patients' assessment of quality
timeFrame: Throughout entire study estimated to take 6 to 12 months to complete
measure: Within each treatment arm, number of events of any use of 2 or more
timeFrame: Throughout entire study estimated to take 6 to 12 months to complete
measure: Within each treatment arm, number of events of any use of two or more
timeFrame: Throughout entire study estimated to take 6 to 12 months to complete
measure: Average time in immediate recovery area before discharge to next phase of care
timeFrame: Throughout entire study estimated to take 6 to 12 months to complete
measure: Average time from dressing complete to modified Aldrete score >8
timeFrame: Throughout entire study estimated to take 6 to 12 months to complete
measure: Within each treatment arm number of composite MACE events in the 30 days
timeFrame: Throughout entire study estimated to take 6 to 12 months to complete
measure: Within each treatment arm number of classic MACE events in the 30 days
timeFrame: Throughout entire study estimated to take 6 to 12 months to complete
measure: Average within treatment arm total dose (mL) of admixture administered
timeFrame: Throughout entire study estimated to take 6 to 12 months to complete
measure: Average within treatment arm total dose (mg) of etomidate during entire case
timeFrame: Throughout entire study estimated to take 6 to 12 months to complete
measure: Average within treatment arm total dose (mg) of propofol during entire case
timeFrame: Throughout entire study estimated to take 6 to 12 months to complete
measure: Average within treatment arm total dose of adjunct sedatives
timeFrame: Throughout entire study estimated to take 6 to 12 months to complete
measure: Within each treatment arm, number of events of any episode of vomiting
timeFrame: Throughout entire study estimated to take 6 to 12 months to complete
measure: Within each treatment arm, number of events of any complaint of nausea
timeFrame: Throughout entire study estimated to take 6 to 12 months to complete
measure: Within each treatment arm, number of events of any syncopal event
timeFrame: Throughout entire study estimated to take 6 to 12 months to complete
measure: Within each treatment arm, number of events of any use of one type of antiemetic drug
timeFrame: Throughout entire study estimated to take 6 to 12 months to complete
measure: Within each treatment arm, number of events of any unanticipated admission
timeFrame: Throughout entire study estimated to take 6 to 12 months to complete
measure: Within each treatment arm, number of events of any airway adjunct usage
timeFrame: Throughout entire study estimated to take 6 to 12 months to complete
measure: Within each treatment arm, number of events of any use of any additional sedatives
timeFrame: Throughout entire study estimated to take 6 to 12 months to complete
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Clements University Hospital
state: Texas
Study officials:
affiliation: University of Texas
name: Kapil Anand
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.