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Enrolling by Invitation

NCT Number: NCT06179485

Effect of Ketamine and Etomidate During RSI on Long Term Outcomes

The RSI-LTO study collects long-term outcomes from the RSI trial (NCT05277896). One-third of adults who are intubated in the ED or ICU experience symptoms of posttraumatic stress disorder (PTSD). PTSD is a psychiatric disorder triggered by a "shocking, scary, or dangerous event." Critical illness, tracheal intubation, and mechanical ventilation can be traumatic and distressing events. Patients may recall the intubation procedure, the feeling of the breathing tube in their throat, or being unable to move ("paralyzed"). While on the breathing machine, patients may experience delirium, frightening hallucinations, and delusions. Patients with PTSD after critical illness can be hypervigilant, anxious, and troubled by intrusive thoughts, nightmares, and flashbacks that last months to years after critical illness and that PTSD negatively impacts patients' marriages, work, and quality of life and increases patients' risk of depression, anxiety, substance use disorder, and suicide. Ketamine may prevent PTSD symptoms by blocking the pathways in the brain's glutaminergic system that are responsible for the formation of traumatic memories In outpatients with chronic PTSD, a single dose of ketamine has been shown to reduce PTSD symptoms for up to 2 weeks. Even a modest reduction in PTSD would translate into tens of thousands of fewer cases of PTSD each year, more cases of PTSD each year than any other medical intervention evaluated to date.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

University of Alabama Hospital, Birmingham, Alabama, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Enrolled in RSI trial (NCT05277896)

Exclusion criteria

  • Aphasic or non-verbal prior to tracheal intubation
  • Cannot follow commands prior to tracheal intubation
  • Non-English speaking
  • Deaf

Treatment and study plan

ketamine

Drug

The RSI-LTO study collects long-term outcomes from the RSI trial (NCT05277896). In the RSI trial, 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). 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.

Etomidate

Drug

The RSI-LTO study collects long-term outcomes from the RSI trial (NCT05277896). In the RSI trial, 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). 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.

Primary outcomes

  1. PTSD Symptoms at 12 months

    Time frame: 12 months

    The investigators will measure PTSD symptoms at 3 and 12 months using the Checklist for Diagnostic and Statistical Manual of Mental Disorders (DSM-5) (PCL-5). The PCL-5 is a widely used 5-10 minute patient survey validated to characterize severity of symptoms of PTSD. Patients rate 20 items corresponding to the DSM-5 criteria for PTSD on a 5-point Likert scale ranging from 0 (not bothersome) to 4 (extremely bothersome). Total scores range from 0 to 80, with higher scores indicating more severe symptoms of PTSD. Because a value for the PCL-5 score will not exist for patients who die prior to assessment, the main analysis will use a composite endpoint approach where patients whose PCL-5 could not be assessed because they died will be assigned a value of 81 (higher than the worst value on the PTSD symptom scale).

Other outcomes

  1. Vital status

    Time frame: 12 months

    Date and location of death will be assessed from enrollment until 12 months after enrollment by trial personnel using review of electronic health records, phone calls with families, and national death indices.

  2. Awareness of paralysis

    Time frame: 3 months

    This will be determined by the modified Brice questionnaire and ICU Memory Tool (15-20 minutes). These semi-structured interviews ask subjects about their recollection of the ICU experience, including of being paralyzed. Possible awareness with paralysis event (Present/Absent) will be defined as: (1)reporting memories of the period between losing consciousness and waking up and (2) a sensation/feeling of wakeful paralysis.

  3. ICU Memories

    Time frame: 3 months

    This will be determined by the ICU Memory Tool (15-20 minutes). These semi-structured interviews ask subjects about their recollection of the ICU experience, including emotions, memories, and the worst thing experienced during mechanical ventilation. Patients will be classified as having (1) factual memories, (2) delusional memories, (3) memories of feelings. These choices are not mutually exclusive as they may have more than one or none of these memories.

  4. Threat perception

    Time frame: 3 months

    This 7-item questionnaire assesses the patient's perception of feeling threatened during the intubation experience. Scores range from 0 (none at all) to 21 (extremely threatened).

  5. Anxiety

    Time frame: 12 months

    Anxiety symptoms will be characterized using the General Anxiety Disorder-7 (GAD-7) which is a 7-item questionnaire that ranges from 0 (no anxiety) to 21 (severe anxiety).

  6. Depression

    Time frame: 12 months

    Depression symptoms will be characterized using the Patient Health Questionnaire-9 (PHQ-9) which is a 9-item questionnaire that ranges from 0 (no depression) to 27 (severe depression).

  7. Quality of life (EQ-5D-5L)

    Time frame: 12 months

    Quality of life will be characterized using the EuroQol 5-Dimension, 5 level version (EQ-5D-5L) is a 5-question instrument that captures impairments in mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. EQ-5D-5L scores will be summarized using the index value validated for the US population. Index scores range range from -0.573 (quality of life worse than death) to 1.000 (perfect quality of life).

  8. Global Cognition

    Time frame: 12 months

    Global cognition will be characterized using the Montreal Cognitive Assessment - Blind (MoCA-Blind). The MoCA-Blind assesses memory, attention, language, abstraction, delayed recall, and orientation. Scores range from 0 (severe cognitive impairment) to 22 (no cognitive impairment).

  9. Executive Function

    Time frame: 12 months

    Oral Trailmaking Test - Patient counts from 1 to 25 and then alternates between numbers and letters (i.e., 1-A-2-B-3-C, etc.,)

  10. Loss of Employment

    Time frame: 12 months

    Patients are asked what their employment status is prior to the acute illness and at 12-months. Patients will be considered to be have loss of employment if they go from: (1) full to partial employment, (2) full to no employment, or (3) partial to no employment.

  11. Physical disability

    Time frame: 12 months

    Duke Activity Status Index (DASI) - An 11-item survey that assesses the patient's current ability to perform various physical activities. Scores range from 0 (poor physical function) to 58.2 (excellent physical function).

Sponsors and collaborators

Lead sponsor

Vanderbilt University Medical Center

Other

Collaborators

  • Patient-Centered Outcomes Research Institute

Registry information

Official study title

Effect of Ketamine and Etomidate During Rapid Sequence Intubation on Long- Term Outcomes (Long-Term Outcomes of the RSI Trial)

Acronym: RSI-LTO

Important dates

Study start
2022
Primary completion
2027
Study completion
2028
First posted
Dec 22, 2023
Registry last updated
Jun 2, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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