NCT05277896

Brief Summary

Among critically ill adults undergoing emergency tracheal intubation, one in five experience hypotension, cardiac arrest, or death. The sedatives used to rapidly induce anesthesia for emergency tracheal intubation have been hypothesized to effect cardiovascular complications and patient outcomes, but the optimal sedative medication for intubation of critically ill adults remains unknown. Ketamine and etomidate are the two most commonly used sedatives during intubation of critically ill adults. Data from a randomized clinical trial are urgently needed to determine the effect of ketamine versus etomidate on cardiovascular complications and clinical outcomes of emergency tracheal intubation.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
2,367

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Apr 2022

Longer than P75 for phase_4

Geographic Reach
1 country

6 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 3, 2022

Completed
11 days until next milestone

First Posted

Study publicly available on registry

March 14, 2022

Completed
23 days until next milestone

Study Start

First participant enrolled

April 6, 2022

Completed
3.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 6, 2025

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 6, 2025

Completed
7 months until next milestone

Results Posted

Study results publicly available

March 25, 2026

Completed
Last Updated

March 25, 2026

Status Verified

March 1, 2026

Enrollment Period

3.4 years

First QC Date

March 3, 2022

Results QC Date

February 18, 2026

Last Update Submit

March 24, 2026

Conditions

Acute Respiratory Failure

Keywords

Critical illnessEmergency airway managementTracheal intubationKetamineEtomidate

Outcome Measures

Primary Outcomes (1)

  • All-cause, 28-day, In-hospital Mortality

    28 days

Secondary Outcomes (1)

  • Cardiovascular Collapse

    from induction to 2 minutes following tracheal intubation

Other Outcomes (17)

  • Cormack-Lehane Grade of Glottic View

    Duration of procedure (minutes)

  • Time From Induction to Successful Tracheal Intubation

    Duration of procedure (minutes)

  • Lowest Oxygen Saturation Between Induction and Two Minutes After Intubation

    from induction to 2 minutes following tracheal intubation

  • +14 more other outcomes

Study Arms (2)

Ketamine Group

ACTIVE COMPARATOR

Patients in the ketamine group will be assigned to receive intravenous ketamine for induction of anesthesia during tracheal intubation. A dose of 2 mg/kg will be recommended, and the group assignment sheet will contain a nomogram providing the recommended dose for a range of patient weights (in pounds and kg). In this pragmatic trial, treating clinicians will be able elect to give a lesser or greater dose of ketamine than recommended if felt to be required for optimal patient care.

Drug: Ketamine

Etomidate Group

ACTIVE COMPARATOR

Patients in the etomidate group will be assigned to receive intravenous etomidate for induction of anesthesia during tracheal intubation. A dose of 0.3 mg/kg will be recommended, and the group assignment sheet will contain a nomogram providing the recommended dose for a range of patient weights (in pounds and kg). In this pragmatic trial, treating clinicians will be able elect to give a lesser or greater dose of etomidate than recommended if felt to be required for optimal patient care.

Drug: Etomidate

Interventions

KetamineDRUG

Intravenous ketamine as the sedative for induction of anesthesia during emergency tracheal intubation

Ketamine Group
EtomidateDRUG

Intravenous etomidate as the sedative for induction of anesthesia during emergency tracheal intubation

Etomidate Group

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patient is critically ill and undergoing emergency tracheal intubation with sedation in an enrolling unit
  • Planned procedure is orotracheal intubation using a laryngoscope
  • Planned operator is a clinician expected to routinely perform tracheal intubation in the participating unit

You may not qualify if:

  • Patient is known to be less than 18 years old
  • Patient is known to be pregnant
  • Patient is known to be a prisoner
  • Patient is known to have an allergy to ketamine or etomidate
  • Patient is presenting to the emergency department with a primary diagnosis of trauma
  • Patient or LAR declines participation during pre-enrollment opt-out conversation or by wearing opt-out bracelet for the RSI trial
  • Clinician feels ketamine is required or contraindicated for the optimal care of the patient
  • Clinician feels etomidate is required or contraindicated for the optimal care of the patient
  • Clinician feels an induction medication other than ketamine or etomidate is required for the optimal care of the patient
  • Immediate need for intubation precludes safe performance of study procedures

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

UAB Hospital

Birmingham, Alabama, 35233, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Denver Health Medical Center

Denver, Colorado, 80204, United States

Location

Hennepin County Medical Center

Minneapolis, Minnesota, 55415, United States

Location

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (3)

  • DeMasi SC, Imhoff B, Lewis AA, Seitz KP, Driver BE, Gibbs KW, Ginde AA, Trent SA, Russell DW, Muhs AL, Prekker ME, Gaillard JP, Resnick-Ault D, Stewart LJ, Whitson MR, Van Schaik GWW, Robinson AE, Palakshappa JA, Aggarwal NR, Brainard JC, Douin DJ, Lyle C, Gandotra S, Lacy AJ, Sherlin KC, Carlson GK, Maycee Cain J, Redman B, Higgins C, Withers C, Beach LL, Gould B, McIntosh J, Lloyd BD, Israel TL, Wang L, Rice TW, Self WH, Han JH, Casey JD, Semler MW. Protocol and Statistical Analysis Plan for a Multicenter Randomized Trial of Ketamine vs Etomidate for Emergency Tracheal Intubation. CHEST Crit Care. 2025 Sep;3(3):100177. doi: 10.1016/j.chstcc.2025.100177. Epub 2025 Aug 13.

    PMID: 41472917DERIVED

  • Casey JD, Seitz KP, Driver BE, Gibbs KW, Ginde AA, Trent SA, Russell DW, Muhs AL, Prekker ME, Gaillard JP, Resnick-Ault D, Stewart LJ, Whitson MR, DeMasi SC, Robinson AE, Palakshappa JA, Aggarwal NR, Brainard JC, Douin DJ, Marvi TK, Scott BK, Alber SM, Lyle C, Gandotra S, Van Schaik GW, Lacy AJ, Sherlin KC, Erickson HL, Cain JM, Redman B, Beach LL, Gould B, McIntosh J, Lewis AA, Lloyd BD, Israel TL, Imhoff B, Wang L, Spicer AB, Churpek MM, Rice TW, Self WH, Han JH, Semler MW; RSI Investigators and the Pragmatic Critical Care Research Group. Ketamine or Etomidate for Tracheal Intubation of Critically Ill Adults. N Engl J Med. 2025 Dec 9:10.1056/NEJMoa2511420. doi: 10.1056/NEJMoa2511420. Online ahead of print.

    PMID: 41369227DERIVED

  • DeMasi SC, Imhoff B, Lewis AA, Seitz KP, Driver BE, Gibbs KW, Ginde AA, Trent SA, Russell DW, Muhs AL, Prekker ME, Gaillard JP, Resnick-Ault D, Stewart LJ, Whitson MR, Van Schaik GWW, Robinson AE, Palakshappa JA, Aggarwal NR, Brainard JC, Douin DJ, Lyle C, Gandotra S, Lacy AJ, Sherlin KC, Carlson GK, Cain JM, Redman B, Higgins C, Withers C, Beach LL, Gould B, McIntosh J, Lloyd BD, Israel TL, Wang L, Rice TW, Self WH, Han JH, Casey JD, Semler MW; RSI investigators and the Pragmatic Critical Care Research Group. Protocol and Statistical Analysis Plan for the Randomized Trial of Sedative Choice for Intubation (RSI). medRxiv [Preprint]. 2025 Jan 18:2025.01.18.25320768. doi: 10.1101/2025.01.18.25320768.

    PMID: 39867415DERIVED

MeSH Terms

Conditions

Critical Illness

Interventions

KetamineEtomidate

Condition Hierarchy (Ancestors)

Disease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

CyclohexanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsImidazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Results Point of Contact

Title
Dr. Matthew W. Semler
Organization
Vanderbilt University Medical Center
matthew.w.semler@vumc.org
615-875-4681

Study Officials

  • Jonathan D Casey, MD, MSc

    Vanderbilt University Medical Center

    PRINCIPAL INVESTIGATOR

  • Matthew W Semler, MD, MSc

    Vanderbilt University Medical Center

    STUDY CHAIR

  • Todd W Rice, MD, MSc

    Vanderbilt University Medical Center

    STUDY DIRECTOR

  • Wesley H Self, MD, MPH

    Vanderbilt University Medical Center

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Assistant Professor

Study Record Dates

First Submitted

March 3, 2022

First Posted

March 14, 2022

Study Start

April 6, 2022

Primary Completion

September 6, 2025

Study Completion

September 6, 2025

Last Updated

March 25, 2026

Results First Posted

March 25, 2026

Record last verified: 2026-03

Data Sharing

IPD Sharing
Will share

Following publication, individual patient data will be made available for sharing to researchers with 1) a signed data access agreement, 2) research testing a hypothesis, 3) a protocol that has been approved by an institutional review board, and 4) a proposal that has received approval from the principal investigator

Shared Documents
STUDY PROTOCOL, SAP, ICF
Time Frame
Following publication. No end date
Access Criteria
1. a signed data access agreement 2. research testing a hypothesis 3. a protocol that has been approved by an institutional review board 4. a proposal that has received approval from the principal investigator

Locations

US(6)