Trial Outcomes & Findings for Ketamine / Propofol Admixture "Ketofol" at Induction in the Critically Ill Against Etomidate: KEEP PACE Trial (NCT NCT02105415)

NCT ID: NCT02105415

Last Updated: 2020-06-16

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2/PHASE3
• Target enrollment: 160 participants
• Primary outcome timeframe: baseline and every 5 minutes up to 15 minutes minutes post study drug administration
• Results posted on: 2020-06-16

Participant Flow

Participant milestones

Measure	Etomidate Etomidate 0.15mg/kg weight based dose	Ketamine / Propofol Admixture Ketamine / Propofol Admixture; weight based dose 0.5 mg/kg ketamine and 0.5 mg/kg propofol.
Overall Study STARTED	76	84
Overall Study COMPLETED	73	79
Overall Study NOT COMPLETED	3	5

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Etomidate n=73 Participants Etomidate 0.15mg/kg weight based dose	Ketamine / Propofol Admixture n=79 Participants Ketamine / Propofol Admixture weight based dose 0.5 mg/kg ketamine and 0.5 mg/kg propofol	Total n=152 Participants Total of all reporting groups
Age, Continuous	60.0 years STANDARD_DEVIATION 18.3 • n=93 Participants	62.1 years STANDARD_DEVIATION 17.2 • n=4 Participants	61.1 years STANDARD_DEVIATION 17.8 • n=27 Participants
Sex: Female, Male Female	35 Participants n=93 Participants	31 Participants n=4 Participants	66 Participants n=27 Participants
Sex: Female, Male Male	38 Participants n=93 Participants	48 Participants n=4 Participants	86 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	57 Participants n=93 Participants	76 Participants n=4 Participants	133 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	16 Participants n=93 Participants	3 Participants n=4 Participants	19 Participants n=27 Participants
Region of Enrollment United States	73 participants n=93 Participants	79 participants n=4 Participants	152 participants n=27 Participants

PRIMARY outcome

Timeframe: baseline and every 5 minutes up to 15 minutes minutes post study drug administration

Population: Data are presented for patients who had blood pressure measurements at baseline (within 15 minutes prior to 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.

Outcome measures

Measure	Etomidate n=70 Participants Etomidate 0.15mg/kg weight based dose	Ketamine / Propofol Admixture n=76 Participants Ketamine / Propofol Admixture weight based dose 0.5 mg/kg ketamine and 0.5 mg/kg propofol	Etomidate (23-25 Hours) Cortisol levels at 23-25 hours	Ketamine/Propofol Admixture (23-25 Hours) Cortisol levels at 23-25 hours
Mean Arterial Pressure Baseline	82.8 mm Hg Standard Deviation 17.9	80.9 mm Hg Standard Deviation 13.3	—	—
Mean Arterial Pressure 5 minutes	81.7 mm Hg Standard Deviation 17.2	77.6 mm Hg Standard Deviation 15.4	—	—
Mean Arterial Pressure 10 minutes	81.9 mm Hg Standard Deviation 20.0	75.3 mm Hg Standard Deviation 20.3	—	—
Mean Arterial Pressure 15 minutes	79.1 mm Hg Standard Deviation 19.5	75.5 mm Hg Standard Deviation 18.1	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Etomidate n=73 Participants Etomidate 0.15mg/kg weight based dose	Ketamine / Propofol Admixture n=79 Participants Ketamine / Propofol Admixture weight based dose 0.5 mg/kg ketamine and 0.5 mg/kg propofol	Etomidate (23-25 Hours) Cortisol levels at 23-25 hours	Ketamine/Propofol Admixture (23-25 Hours) Cortisol levels at 23-25 hours
Mortality	26 Participants	25 Participants	—	—

SECONDARY outcome

Timeframe: up to 24 hours post study drug administration

Population: Data are presented for patients who had vasopressor data within the time frame

The use of vasoactive medications to restore the blood pressure post-administration in the ketamine/propofol combination as compared to the etomidate group.

Outcome measures

Measure	Etomidate n=73 Participants Etomidate 0.15mg/kg weight based dose	Ketamine / Propofol Admixture n=79 Participants Ketamine / Propofol Admixture weight based dose 0.5 mg/kg ketamine and 0.5 mg/kg propofol	Etomidate (23-25 Hours) Cortisol levels at 23-25 hours	Ketamine/Propofol Admixture (23-25 Hours) Cortisol levels at 23-25 hours
Vasopressor Use Pre-treament	1 Participants	5 Participants	—	—
Vasopressor Use New-onset pressors (within 3 minutes)	12 Participants	18 Participants	—	—
Vasopressor Use Delayed-onset pressors (within 24 hours)	57 Participants	64 Participants	—	—

SECONDARY outcome

Timeframe: up to 24 hours post study drug administration

Population: A secondary outcome included adrenal testing in a subset of patients. Thus, cortisol levels were available for 29 subjects at 3 and 5 hours and 30 subjects at 23 and 25 hours.

Incidence of adrenal insufficiency between ketamine/propofol admixture and etomidate. Adrenal insuffiency was evaluated with co-syntropin stimulation test.

Outcome measures

Measure	Etomidate n=16 Participants Etomidate 0.15mg/kg weight based dose	Ketamine / Propofol Admixture n=13 Participants Ketamine / Propofol Admixture weight based dose 0.5 mg/kg ketamine and 0.5 mg/kg propofol	Etomidate (23-25 Hours) n=15 Participants Cortisol levels at 23-25 hours	Ketamine/Propofol Admixture (23-25 Hours) n=15 Participants Cortisol levels at 23-25 hours
Number of Participants With Adrenal Insufficiency	13 Participants	5 Participants	9 Participants	6 Participants

SECONDARY outcome

Timeframe: hospital discharge or day 28, whichever comes first

comparison of mechanical ventilation free days between the two groups

Outcome measures

Measure	Etomidate n=73 Participants Etomidate 0.15mg/kg weight based dose	Ketamine / Propofol Admixture n=79 Participants Ketamine / Propofol Admixture weight based dose 0.5 mg/kg ketamine and 0.5 mg/kg propofol	Etomidate (23-25 Hours) Cortisol levels at 23-25 hours	Ketamine/Propofol Admixture (23-25 Hours) Cortisol levels at 23-25 hours
Mechanical Ventilation Free Days	22 days Interval 0.0 to 25.0	20 days Interval 0.0 to 26.0	—	—

SECONDARY outcome

Timeframe: hospital discharge or day 28, whichever comes first

blood product transfusions [Red Blood Cells vs. non-Red Blood Cells] between the two groups

Outcome measures

Measure	Etomidate n=73 Participants Etomidate 0.15mg/kg weight based dose	Ketamine / Propofol Admixture n=79 Participants Ketamine / Propofol Admixture weight based dose 0.5 mg/kg ketamine and 0.5 mg/kg propofol	Etomidate (23-25 Hours) Cortisol levels at 23-25 hours	Ketamine/Propofol Admixture (23-25 Hours) Cortisol levels at 23-25 hours
Blood Product Transfusions Red blood cell	21 Participants	13 Participants	—	—
Blood Product Transfusions Non-red blood cell	16 Participants	8 Participants	—	—
Blood Product Transfusions Colloid	28 Participants	26 Participants	—	—

SECONDARY outcome

Timeframe: hospital discharge or day 28, whichever comes first

comparison of intensive care unit free days between the two groups

Outcome measures

Measure	Etomidate n=73 Participants Etomidate 0.15mg/kg weight based dose	Ketamine / Propofol Admixture n=79 Participants Ketamine / Propofol Admixture weight based dose 0.5 mg/kg ketamine and 0.5 mg/kg propofol	Etomidate (23-25 Hours) Cortisol levels at 23-25 hours	Ketamine/Propofol Admixture (23-25 Hours) Cortisol levels at 23-25 hours
Intensive Care Unit Free Days	16 days Interval 0.0 to 23.0	17 days Interval 0.0 to 24.0	—	—

SECONDARY outcome

Timeframe: up to 24 hours post study drug administration

Population: The analysis of new onset delirium was restricted to subjects (54 etomidate, 62 KPA) who did not experience delirium pre-study drug.

Comparison of number of participants who were positive for delirium using CAM-ICU between groups

Outcome measures

Measure	Etomidate n=54 Participants Etomidate 0.15mg/kg weight based dose	Ketamine / Propofol Admixture n=62 Participants Ketamine / Propofol Admixture weight based dose 0.5 mg/kg ketamine and 0.5 mg/kg propofol	Etomidate (23-25 Hours) Cortisol levels at 23-25 hours	Ketamine/Propofol Admixture (23-25 Hours) Cortisol levels at 23-25 hours
Number of Participants Experiencing Delirium Using Confusion Assessment Method in ICU	7 Participants	4 Participants	—	—

Adverse Events

Etomidate

Serious events: 6 serious events

Other events: 19 other events

Deaths: 26 deaths

Ketamine / Propofol Admixture

Serious events: 5 serious events

Other events: 14 other events

Deaths: 25 deaths

Serious adverse events

Measure	Etomidate n=73 participants at risk Etomidate 0.15mg/kg weight based dose	Ketamine / Propofol Admixture n=79 participants at risk Ketamine / Propofol Admixture weight based dose 0.5 mg/kg ketamine and 0.5 mg/kg propofol
Cardiac disorders Cardiac arrest	0.00% 0/73 • Given the context of the study and the emergent nature in which the interventions were conducted, adverse events were collected up to 72 hours after enrollment.	2.5% 2/79 • Given the context of the study and the emergent nature in which the interventions were conducted, adverse events were collected up to 72 hours after enrollment.
Vascular disorders Hypertensive urgency	2.7% 2/73 • Given the context of the study and the emergent nature in which the interventions were conducted, adverse events were collected up to 72 hours after enrollment.	0.00% 0/79 • Given the context of the study and the emergent nature in which the interventions were conducted, adverse events were collected up to 72 hours after enrollment.
Vascular disorders Severe hypotension	5.5% 4/73 • Given the context of the study and the emergent nature in which the interventions were conducted, adverse events were collected up to 72 hours after enrollment.	3.8% 3/79 • Given the context of the study and the emergent nature in which the interventions were conducted, adverse events were collected up to 72 hours after enrollment.

Other adverse events

Measure	Etomidate n=73 participants at risk Etomidate 0.15mg/kg weight based dose	Ketamine / Propofol Admixture n=79 participants at risk Ketamine / Propofol Admixture weight based dose 0.5 mg/kg ketamine and 0.5 mg/kg propofol
Respiratory, thoracic and mediastinal disorders Intubation Complication	1.4% 1/73 • Number of events 1 • Given the context of the study and the emergent nature in which the interventions were conducted, adverse events were collected up to 72 hours after enrollment.	2.5% 2/79 • Number of events 2 • Given the context of the study and the emergent nature in which the interventions were conducted, adverse events were collected up to 72 hours after enrollment.
General disorders IV infiltration	2.7% 2/73 • Number of events 2 • Given the context of the study and the emergent nature in which the interventions were conducted, adverse events were collected up to 72 hours after enrollment.	0.00% 0/79 • Given the context of the study and the emergent nature in which the interventions were conducted, adverse events were collected up to 72 hours after enrollment.
General disorders Multi organ failure	5.5% 4/73 • Number of events 4 • Given the context of the study and the emergent nature in which the interventions were conducted, adverse events were collected up to 72 hours after enrollment.	1.3% 1/79 • Number of events 1 • Given the context of the study and the emergent nature in which the interventions were conducted, adverse events were collected up to 72 hours after enrollment.
Respiratory, thoracic and mediastinal disorders Respiratory failure	2.7% 2/73 • Number of events 2 • Given the context of the study and the emergent nature in which the interventions were conducted, adverse events were collected up to 72 hours after enrollment.	7.6% 6/79 • Number of events 6 • Given the context of the study and the emergent nature in which the interventions were conducted, adverse events were collected up to 72 hours after enrollment.
Cardiac disorders Tachycardia	2.7% 2/73 • Number of events 2 • Given the context of the study and the emergent nature in which the interventions were conducted, adverse events were collected up to 72 hours after enrollment.	0.00% 0/79 • Given the context of the study and the emergent nature in which the interventions were conducted, adverse events were collected up to 72 hours after enrollment.
General disorders Vomiting/Aspiration	4.1% 3/73 • Number of events 3 • Given the context of the study and the emergent nature in which the interventions were conducted, adverse events were collected up to 72 hours after enrollment.	2.5% 2/79 • Number of events 2 • Given the context of the study and the emergent nature in which the interventions were conducted, adverse events were collected up to 72 hours after enrollment.
Cardiac disorders arrythmia	1.4% 1/73 • Number of events 1 • Given the context of the study and the emergent nature in which the interventions were conducted, adverse events were collected up to 72 hours after enrollment.	0.00% 0/79 • Given the context of the study and the emergent nature in which the interventions were conducted, adverse events were collected up to 72 hours after enrollment.
Vascular disorders shock	5.5% 4/73 • Number of events 4 • Given the context of the study and the emergent nature in which the interventions were conducted, adverse events were collected up to 72 hours after enrollment.	3.8% 3/79 • Number of events 3 • Given the context of the study and the emergent nature in which the interventions were conducted, adverse events were collected up to 72 hours after enrollment.

Additional Information

Dr. Nathan Smischney

Mayo Clinic

Phone: 507-255-4305

Email: smischney.nathan@mayo.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place