Critical IllnessPhase 2/3KEEP PACENCT02105415
Ketamine / Propofol Admixture "Ketofol" at Induction in the Critically Ill Against Etomidate: KEEP PACE Trial
A Phase 2/3 study testing Ketamine / Propofol Admixture and Etomidate in people with Critical Illness, run by Mayo Clinic at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Critical Illness
- What is being tested?
- Ketamine / Propofol Admixture and Etomidate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 160 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2014to 1 Aug 2018
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Critical Illness
- Being tested
- Ketamine / Propofol Admixture, Etomidate
- Keywords
- Critical care, Emergent, Etomidate, Hemodynamics, Intensive care unit, Intubation, Ketamine-Propofol admixture
- Medical subject headings
- Critical Illness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketamine / Propofol AdmixtureDrug
EtomidateDrug
| Study group | Role | What they receive |
|---|---|---|
| Etomidate | Active comparator | weight based dose of 0.15mg/kg Receives: Drug: Etomidate |
| Ketamine / Propofol Admixture | Experimental | weight based dose of 0.5mg/kg of ketamine and 0.5mg/kg of propofol Receives: Drug: Ketamine / Propofol Admixture |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: baseline and every 5 minutes up to 15 minutes minutes post study drug administration
Secondary outcomes (7)
Mortality
In-hospital/28 day mortality among patients in ketamine/propofol combination compared to in-hospital/28-day mortality in etomidate.
Measured: 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.
Measured: 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.
Measured: up to 24 hours post study drug administration
Mechanical Ventilation Free Days
comparison of mechanical ventilation free days between the two groups
Measured: 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
Measured: hospital discharge or day 28, whichever comes first
Intensive Care Unit Free Days
comparison of intensive care unit free days between the two groups
Measured: 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
Measured: up to 24 hours post study drug administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2014 (estimated)
- Study startApr 2014
- Primary completion28 Nov 2017
- Study completion1 Aug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Critical IllnessStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 160 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nathan J. Smischney, Mayo Clinic
- Investigators
- Nathan J Smischney, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02105415
- Sponsor's protocol ID
- 13-000506
- Acronym
- KEEP PACE
- Status last verified
- May 2020
- First submitted
- 31 Mar 2014
- Last updated
- 16 Jun 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Smischney NJ, Seisa MO, Schroeder DR. Association of Shock Indices with Peri-Intubation Hypotension and Other Outcomes: A Sub-Study of the KEEP PACE Trial. J Intensive Care Med. 2024 Sep;39(9):866-874. doi: 10.1177/08850666241235591. Epub 2024 Feb 25.
PubMed 38403984Smischney 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.
PubMed 31335755Smischney 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.
PubMed 25909406
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ketamine / Propofol Admixture "Ketofol" at Induction in the Critically Ill Against Etomidate: KEEP PACE Trial
- ClinicalTrials.gov ID
- NCT02105415
- Acronym / sponsor ID
- KEEP PACE / 13-000506
- Conditions
- Critical Illness
- Keywords
- Critical care, Emergent, Etomidate, Hemodynamics, Intensive care unit, Intubation, Ketamine-Propofol admixture
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 160 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- Apr 2014
- Primary completion
- 28 Nov 2017 (actual)
- Study completion
- 1 Aug 2018 (actual)
- First posted
- 7 Apr 2014 (estimated)
- Results
- Posted 11 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Etomidate | Active comparator | Drug: Etomidateweight based dose of 0.15mg/kg |
| Ketamine / Propofol Admixture | Experimental | Drug: Ketamine / Propofol Admixtureweight based dose of 0.5mg/kg of ketamine and 0.5mg/kg of propofol |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (10 listed)
- Known intracranial pathology
- Known chronic opiate-dependence
- Received continuous sedative infusion in the last 24 hours
- Known severe psychiatric illness
- Known egg allergies
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ketamine / Propofol Admixture | Drug | Ketamine / Propofol Admixture |
| Etomidate | Drug | Etomidate |
Primary outcome
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.
7 secondary outcomes
Mortality
Time frame: Hospital Discharge or Day 28, whichever comes first
Vasopressor Use
Time frame: up to 24 hours post study drug administration
Number of Participants With Adrenal Insufficiency
Time frame: up to 24 hours post study drug administration
Mechanical Ventilation Free Days
Time frame: hospital discharge or day 28, whichever comes first
Blood Product Transfusions
Time frame: hospital discharge or day 28, whichever comes first
Intensive Care Unit Free Days
Time frame: hospital discharge or day 28, whichever comes first
Number of Participants Experiencing Delirium Using Confusion Assessment Method in ICU
Time frame: up to 24 hours post study drug administration
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jun 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38403984Smischney NJ, Seisa MO, Schroeder DR. Association of Shock Indices with Peri-Intubation Hypotension and Other Outcomes: A Sub-Study of the KEEP PACE Trial. J Intensive Care Med. 2024 Sep;39(9):866-874. doi: 10.1177/08850666241235591. Epub 2024 Feb 25.
- Derived from this study: PubMed 31335755Smischney 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.
- Derived from this study: PubMed 25909406Smischney 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nathan J Smischney, MD principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Ketamine / Propofol Admixture and Etomidate in people with Critical Illness, run by Mayo Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Arterial Pressure (time frame: baseline and every 5 minutes up to 15 minutes minutes post study drug administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02105415, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jun 2020.