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

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ClinicalTrials.gov Identifier: NCT02105415
Recruitment Status : Completed
First Posted : April 7, 2014
Results First Posted : January 11, 2019
Last Update Posted : June 16, 2020
Sponsor:
Information provided by (Responsible Party):
Nathan J. Smischney, Mayo Clinic

Tracking Information
First Submitted Date  ICMJE March 31, 2014
First Posted Date  ICMJE April 7, 2014
Results First Submitted Date  ICMJE November 26, 2018
Results First Posted Date  ICMJE January 11, 2019
Last Update Posted Date June 16, 2020
Study Start Date  ICMJE April 2014
Actual Primary Completion Date November 28, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 19, 2018)
Mean Arterial Pressure [ Time Frame: baseline and every 5 minutes up to 15 minutes minutes post study drug administration ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 4, 2014)
Mean Arterial Pressure [ Time Frame: 15 minutes post study drug administration ]
Primary Specific Aim: To determine if the decrease in mean arterial pressure for the ketamine/propofol group at a 1:1 dose ratio is lower as 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. Hypothesis: The decrease in mean arterial pressure for the ketamine/propofol arm will be reduced as compared to the etomidate arm during the first 15 minutes post-administration within the population of critically ill patients needing urgent and/or emergent endotracheal intubation.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 19, 2018)
  • Mortality [ Time Frame: Hospital Discharge or Day 28, whichever comes first ]
    In-hospital/28 day mortality among patients in ketamine/propofol combination compared to in-hospital/28-day mortality in etomidate.
  • Vasopressor Use [ Time Frame: up to 24 hours post study drug administration ]
    The use of vasoactive medications to restore the blood pressure post-administration in the ketamine/propofol combination as compared to the etomidate group.
  • Number of Participants With Adrenal Insufficiency [ Time Frame: up to 24 hours post study drug administration ]
    Incidence of adrenal insufficiency between ketamine/propofol admixture and etomidate. Adrenal insuffiency was evaluated with co-syntropin stimulation test.
  • Mechanical Ventilation Free Days [ Time Frame: hospital discharge or day 28, whichever comes first ]
    comparison of mechanical ventilation free days between the two groups
  • Blood Product Transfusions [ Time Frame: hospital discharge or day 28, whichever comes first ]
    blood product transfusions [Red Blood Cells vs. non-Red Blood Cells] between the two groups
  • Intensive Care Unit Free Days [ Time Frame: hospital discharge or day 28, whichever comes first ]
    comparison of intensive care unit free days between the two groups
  • Number of Participants Experiencing Delirium Using Confusion Assessment Method in ICU [ Time Frame: up to 24 hours post study drug administration ]
    Comparison of number of participants who were positive for delirium using CAM-ICU between groups
Original Secondary Outcome Measures  ICMJE
 (submitted: April 4, 2014)
  • Mortality [ Time Frame: Hosptial Discharge or Day 28, whichever comes first ]
    Secondary Specific Aim 1: To determine whether this admixture is associated with decreased 28-day mortality as compared to etomidate in the critically ill. Hypothesis 1: The 28 day mortality among patients in the ketamine/propofol combination will be decreased as compared to the 28-day mortality in the etomidate arm.
  • Vasopressor Use [ Time Frame: up to 1 hour post study drug administration ]
    Secondary Specific Aim 2: To determine if this admixture is associated with decreased use of vasoactive medication administration (e.g., dopamine, phenylephrine, norepinephrine, epinephrine or vasopressin) from time 0 to 1 hour post-administration as compared to etomidate in the critically ill. Hypothesis 2: The use of vasoactive medications to restore the blood pressure post-administration will be reduced in the ketamine/propofol combination as compared to the etomidate group.
  • adrenal insufficiency [ Time Frame: up to 24 hours post study drug administration ]
    Secondary Specific Aim 3: To determine if this admixture is associated with a decreased incidence of adrenal insufficiency, defined as a pre-cosyntropin cortisol of less than 10ug/dL or if the post-cosyntropin cortisol increased by less than 9ug/dL after 250uq of cosyntropin, as compared to etomidate in the critically ill. Hypothesis 3: The use of ketamine/propofol admixture will be associated with a reduced incidence of adrenal insufficiency as compared to etomidate.
  • Mechanical Ventilation Free Days [ Time Frame: hospital discharge or day 28, whichever comes first ]
    comparison of mechanical ventilation free days between the two groups
  • Blood Product Transfusions [ Time Frame: hospital discharge or day 28, whichever comes first ]
    Number of blood product transfusions between the two groups
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ketamine / Propofol Admixture "Ketofol" at Induction in the Critically Ill Against Etomidate: KEEP PACE Trial
Official Title  ICMJE Ketamine / Propofol Admixture "Ketofol" at Induction in the Critically Ill Against Etomidate: KEEP PACE Trial
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Critical Illness
Intervention  ICMJE
  • Drug: Ketamine / Propofol Admixture
  • Drug: Etomidate
Study Arms  ICMJE
  • Active Comparator: Etomidate
    weight based dose of 0.15mg/kg
    Intervention: Drug: Etomidate
  • Experimental: Ketamine / Propofol Admixture
    weight based dose of 0.5mg/kg of ketamine and 0.5mg/kg of propofol
    Intervention: Drug: Ketamine / Propofol Admixture
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 4, 2014)
160
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE August 1, 2018
Actual Primary Completion Date November 28, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02105415
Other Study ID Numbers  ICMJE 13-000506
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
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Nathan J. Smischney, Mayo Clinic
Study Sponsor  ICMJE Mayo Clinic
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Nathan J Smischney, MD Mayo Clinic
PRS Account Mayo Clinic
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP