Ketamine / Propofol Admixture "Ketofol" at Induction in the Critically Ill Against Etomidate: KEEP PACE Trial (KEEP PACE)

The hypothesis of this study is that a Ketamine / Propofol mixture will produce more stable hemodynamics as compared to Etomidate during emergent intubations in the intensive care unit. Patients that require a breathing tube to be placed in the ICU will be randomized to receIve either a Ketamine / Propofol mixture or Etomidate for sedation in order to place the breathing tube.

Study Overview

• Status: Completed
• Conditions: Critical Illness
• Intervention / Treatment: Drug: Etomidate; Drug: Ketamine / Propofol Admixture

Detailed Description

Endotracheal intubation is a procedure that may cause significant hemodynamic perturbations and can severely impact the outcome of the critically ill. To ensure a safe outcome during this particular procedure, there are many factors that the clinician is faced with. One decision that confronts the critical care physician involves the correct combination of medications with which to facilitate such a safe outcome. Given the reported hemodynamic stability, etomidate is a medication that is chosen by many providers in this particular situation. However, its association with a possible increase in mortality makes it less than ideal for a number of critical care physicians. In recent years, an admixture of propofol and ketamine has been studied that demonstrates hemodynamic stability based on the balancing of the hemodynamic effects of these two individual agents alone. This novel medication combination, sometimes referred to as "ketofol", may offer a valuable alternative to the critical care physician. Therefore, a randomized parallel-group clinical trial of adult critically ill patients admitted to a medical and/or surgical intensive care unit at Mayo Clinic Rochester who meet the criteria designated below for which urgent and/or emergent intubation is needed will receive one of two interventions based on stratified randomization. The "active" intervention arm will receive ketamine/propofol (ketofol) to facilitate endotracheal intubation. The comparison arm will receive etomidate. The primary outcome will focus on hemodynamic data recorded during the first 5 minutes post-administration with secondary outcomes looking at hemodynamic data at 10 and 15 minutes and addressing intensive care unit length of stay, mortality, adrenal function, and vasoactive medication use, among others.

• Study Type: Interventional
• Enrollment (Actual): 160
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 years of age or older
• Surgical or medical intensive care unity patients requiring endotracheal intubation
• Consulting physician agrees to study plan and will follow drug randomization

Exclusion Criteria:

• Known intracranial pathology
• Known chronic opiate-dependence
• Received continuous sedative infusion in the last 24 hours
• Known severe psychiatric illness
• Known egg allergies
• Known contraindication to fentanyl, midazolam, ketamine, propofol or etomidate
• Intubation in which standard practice is not to use sedation
• No known documented weight or weight greater than 140 kg or less than 30 kg
• Prior participation in the study
• Of childbearing age (18-50) with no known negative pregnancy test on this admission.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Etomidate; weight based dose of 0.15mg/kg	Drug: Etomidate
Experimental: Ketamine / Propofol Admixture; weight based dose of 0.5mg/kg of ketamine and 0.5mg/kg of propofol	Drug: Ketamine / Propofol Admixture

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Arterial Pressure	Mean arterial pressure for the ketamine/propofol group at a 1:1 dose ratio compared to the etomidate group within the first 15 minutes post-administration in patients in need of urgent and/or emergent endotracheal intubation, as defined by any intubation within the intensive care unit excluding intubations for elective procedural events and codes.	baseline and every 5 minutes up to 15 minutes minutes post study drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	In-hospital/28 day mortality among patients in ketamine/propofol combination compared to in-hospital/28-day mortality in etomidate.	Hospital Discharge or Day 28, whichever comes first
Vasopressor Use	The use of vasoactive medications to restore the blood pressure post-administration in the ketamine/propofol combination as compared to the etomidate group.	up to 24 hours post study drug administration
Number of Participants With Adrenal Insufficiency	Incidence of adrenal insufficiency between ketamine/propofol admixture and etomidate. Adrenal insuffiency was evaluated with co-syntropin stimulation test.	up to 24 hours post study drug administration
Mechanical Ventilation Free Days	comparison of mechanical ventilation free days between the two groups	hospital discharge or day 28, whichever comes first
Blood Product Transfusions	blood product transfusions [Red Blood Cells vs. non-Red Blood Cells] between the two groups	hospital discharge or day 28, whichever comes first
Intensive Care Unit Free Days	comparison of intensive care unit free days between the two groups	hospital discharge or day 28, whichever comes first
Number of Participants Experiencing Delirium Using Confusion Assessment Method in ICU	Comparison of number of participants who were positive for delirium using CAM-ICU between groups	up to 24 hours post study drug administration

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Nathan J Smischney, MD, Mayo Clinic

Publications and helpful links

General Publications

• Smischney NJ, Nicholson WT, Brown DR, Gallo De Moraes A, Hoskote SS, Pickering B, Oeckler RA, Iyer VN, Gajic O, Schroeder DR, Bauer PR. Ketamine/propofol admixture vs etomidate for intubation in the critically ill: KEEP PACE Randomized clinical trial. J Trauma Acute Care Surg. 2019 Oct;87(4):883-891. doi: 10.1097/TA.0000000000002448.
• Smischney NJ, Hoskote SS, Gallo de Moraes A, Racedo Africano CJ, Carrera PM, Tedja R, Pannu JK, Hassebroek EC, Reddy DR, Hinds RF, Thakur L. Ketamine/propofol admixture (ketofol) at induction in the critically ill against etomidate (KEEP PACE trial): study protocol for a randomized controlled trial. Trials. 2015 Apr 21;16:177. doi: 10.1186/s13063-015-0687-0.

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): November 28, 2017
• Study Completion (Actual): August 1, 2018

Study Registration Dates

• First Submitted: March 31, 2014
• First Submitted That Met QC Criteria: April 4, 2014
• First Posted (Estimate): April 7, 2014

Study Record Updates

• Last Update Posted (Actual): June 16, 2020
• Last Update Submitted That Met QC Criteria: May 28, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Intensive care unit; Critical care; Intubation; Hemodynamics; Etomidate; Emergent; Ketamine-Propofol admixture
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Hypnotics and Sedatives; Ketamine; Propofol; Etomidate
• Other Study ID Numbers: 13-000506

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No