Ket-RSI: Evaluating the Hemodynamic Effects of Ketamine Versus Etomidate During Rapid Sequence Intubation

• Sponsor: South East Area Health Education Center, Wilmington, NC (Other)
• Overall Status: Completed
• CT.gov ID: NCT03545503
• Collaborator: New Hanover Regional Medical Center (Other)
• Enrollment: 428
• Location: 1
• Arms: 2
• Actual Duration (Months): 20
• Patients Per Site Per Month: 21.4

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the hemodynamic effects of ketamine v etomidate during rapid sequence intubation (RSI) in the pre-hospital and emergency department setting.

Condition or Disease	Intervention/Treatment	Phase
Intubation Complication	Drug: Etomidate; Drug: Ketamine	Phase 4

Detailed Description

This is a randomized prospective study evaluating the hemodynamic response in adult participants greater than or equal to 18 years of age undergoing RSI in the pre-hospital or emergency department setting. Hemodynamic response is the cardiology response of the circulatory system. The investigators will compare the drugs Ketamine and Etomidate in participants having RSI. Ketamine and Etomidate are immediately available for RSI in both settings as both are currently standards of care for RSI.

Research thus far demonstrates that both Etomidate and ketamine are safe and effective for RSI. Despite the reported safety of Ketamine, Etomidate usage continues to far surpass that of ketamine. Both Etomidate and Ketamine are FDA-approved for induction of anesthesia. They are both ideal drugs for intubation due to their pharmacokinetic properties including a quick onset of less than 60 seconds, a short duration of about 10 minutes, and the minimal effect they have on the cardiovascular system. The neutral effect on the cardiovascular system is particularly important in the acute and traumatic setting when patients are often hypotensive.

However, there are some differences and disadvantages in the two medications. Due to these factors and limited data to support Ketamine as an equal or superior alternative to Etomidate, it has been difficult to clearly recommend one agent over the other for RSI.

Data will be analyzed using SPSS with a p-value of less than 0.05 being considered significant. The PI will consider a 20% decrease in systolic BP from a participant baseline as significant, and will compare the incidence of post RSI hypotension between the two groups. Several a priori subgroups will be evaluated to include patients greater than 70 years of age, trauma participants requiring RSI, and those participants whose shock index is less than 0.9 versus those whose shock index is greater than 0.9.

To maintain 80% power with a probability of 0.05, 200 participants will be needed in each arm to detect at 25% difference in SBP (baseline to post drug administration effects)

Study Design

• Study Type: Interventional
• Actual Enrollment: 428 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Controlled Trial to Evaluate the Hemodynamic Effects of Ketamine Versus Etomidate During Rapid Sequence Intubation
• Actual Study Start Date: Jan 1, 2018
• Actual Primary Completion Date: Sep 1, 2019
• Actual Study Completion Date: Sep 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Etomidate Etomidate will be dosed once at a standard of 0.3 mg/kg via IV Push	Drug: Etomidate; Etomidate will be administered as the sedative for RSI on even days; Other Names: Amidate
Active Comparator: Ketamine Ketamine will be dosed once at a standard 2 mg/kg via IV Push	Drug: Ketamine; Ketamine will be administered as the sedative for RSI on odd days; Other Names: Ketalar

Outcome Measures

Primary Outcome Measures

1. Hemodynamic Effect as Measured by Systolic Blood Pressure Before and After RSI [The hemodynamic response will be measured by assessing the change in vital signs between 15 minutes prior to administration and vitals up to 15 minutes after the administration of the study drug.]

   The primary outcome of this study is to determine the change in hemodynamic response comparing systolic blood pressure pre-versus post-administration of study drug. A significant hemodynamic response is defined as a decrease in systolic blood pressure of 20% or greater between the pre versus post administered study drug.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Persons greater than 18yrs requiring rapid sequence intubation for any reason.

Exclusion Criteria:

• Pregnant patients

• Children under the age of 18

• Patients with a known hypersensitivity to etomidate or ketamine

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	New Hanover Regional Medical Center	Wilmington	North Carolina	United States	28401

Sponsors and Collaborators

• South East Area Health Education Center, Wilmington, NC
• New Hanover Regional Medical Center

Investigators

• Principal Investigator: William F Powers IV, MD, New Hanover Regional Medical Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 1, 2017

More Information

Publications

None provided.

• Responsible Party: William F Powers, IV, MD, Assistant Professor of Surgery, South East Area Health Education Center, Wilmington, NC
• ClinicalTrials.gov Identifier: NCT03545503
• Other Study ID Numbers: 1712-4
• First Posted: Jun 4, 2018
• Last Update Posted: Nov 26, 2021
• Last Verified: Oct 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by William F Powers, IV, MD, Assistant Professor of Surgery, South East Area Health Education Center, Wilmington, NC: Rapid Sequence Intubation; Hemodynamics; Etomidate; Ketamine
• Additional relevant MeSH terms: Ketamine; Etomidate

Study Results

Participant Flow

Recruitment Details	Participants were recruited if they required rapid sequence intubation in the pre-hospital or 17th street campus emergency department setting between January 1, 2018 and July 30, 2019.
Pre-assignment Detail	98 did not meet inclusion criteria, 48 had incomplete sedative data, and 71 were excluded for other reasons

Arm/Group Title	Etomidate	Ketamine
Arm/Group Description	Etomidate will be dosed once at a standard of 0.3 mg/kg via IV Push Etomidate: Etomidate will be administered as the sedative for RSI on even days	Ketamine will be dosed once at a standard 2 mg/kg via IV Push Ketamine: Ketamine will be administered as the sedative for RSI on odd days
Period Title: Overall Study
STARTED	208	220
COMPLETED	194	204
NOT COMPLETED	14	16

Baseline Characteristics

Arm/Group Title	Etomidate	Ketamine	Total
Arm/Group Description	Etomidate will be dosed once at a standard of 0.3 mg/kg via IV Push Etomidate: Etomidate will be administered as the sedative for RSI on even days	Ketamine will be dosed once at a standard 2 mg/kg via IV Push Ketamine: Ketamine will be administered as the sedative for RSI on odd days	Total of all reporting groups
Overall Participants	194	204	398
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.48 (19.5)	56.68 (19.68)	57.08 (19.57)
Sex: Female, Male (Count of Participants)
Female	67 34.5%	74 36.3%	141 35.4%
Male	127 65.5%	130 63.7%	257 64.6%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%

Outcome Measures

1. Primary Outcome

Title	Hemodynamic Effect as Measured by Systolic Blood Pressure Before and After RSI
Description	The primary outcome of this study is to determine the change in hemodynamic response comparing systolic blood pressure pre-versus post-administration of study drug. A significant hemodynamic response is defined as a decrease in systolic blood pressure of 20% or greater between the pre versus post administered study drug.
Time Frame	The hemodynamic response will be measured by assessing the change in vital signs between 15 minutes prior to administration and vitals up to 15 minutes after the administration of the study drug.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Etomidate	Ketamine
Arm/Group Description	Participants randomized to receive etomidate	Participants randomized to receive ketamine
Measure Participants	194	204
Pre-SBP	138.04 (38.63)	132.39 (39.54)
Post SBP 0-7	139.09 (44.52)	130.09 (41.78)
Post SBP 8-15	130.42 (42.19)	120.80 (37.37)

Adverse Events

Time Frame	24 hours
Arm/Group Title	Etomidate		Ketamine
Arm/Group Description	Participants receiving etomidate		Participants receiving ketamine
All Cause Mortality
	Etomidate		Ketamine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/194 (0%)		0/204 (0%)
Serious Adverse Events
	Etomidate		Ketamine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/194 (0%)		1/204 (0.5%)
Vascular disorders
Hypertension	0/194 (0%)		1/204 (0.5%)
Other (Not Including Serious) Adverse Events
	Etomidate		Ketamine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	117/194 (60.3%)		111/204 (54.4%)
Vascular disorders
Hypertension	117/194 (60.3%)		111/204 (54.4%)
Hypotension	36/194 (18.6%)		53/204 (26%)

Limitations/Caveats

Investigators nor clinicians were blinded to study drug. Resuscitation pre-RSI was not accounted for nor was the dosing for vascopressors. We could not control the slow administration of ketamine to decrease effects of hypotension due to rapid administration.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.