Trial Outcomes & Findings for Ketamine Versus Etomidate for Rapid Sequence Intubation (NCT NCT01823328)

NCT ID: NCT01823328

Last Updated: 2019-05-24

Results Overview

\*Maximum SOFA score within three hospital days: all patients. SOFA score is the Sequential Organ Failure Assessment. The minimum score is 0, the maximum score is 24, with higher scores indicating higher likelihood of worse outcome.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 143 participants
• Primary outcome timeframe: up to 3 days
• Results posted on: 2019-05-24

Participant Flow

14 patients withdrew consent.

Participant milestones

Measure	Ketamine Subjects in the ketamine arm will receive ketamine for sedation prior to rapid sequence intubation (RSI). Ketamine: Subjects will receive ketamine for sedation prior to rapid sequence intubation.	Etomidate Subjects in the etomidate arm will receive etomidate for sedation prior to rapid sequence intubation (RSI). Etomidate: Subjects will receive etomidate for sedation prior to rapid sequence intubation.
Overall Study STARTED	70	73
Overall Study COMPLETED	62	67
Overall Study NOT COMPLETED	8	6

Reasons for withdrawal

Measure	Ketamine Subjects in the ketamine arm will receive ketamine for sedation prior to rapid sequence intubation (RSI). Ketamine: Subjects will receive ketamine for sedation prior to rapid sequence intubation.	Etomidate Subjects in the etomidate arm will receive etomidate for sedation prior to rapid sequence intubation (RSI). Etomidate: Subjects will receive etomidate for sedation prior to rapid sequence intubation.
Overall Study Withdrawal by Subject	8	6

Baseline Characteristics

Ketamine Versus Etomidate for Rapid Sequence Intubation

Baseline characteristics by cohort

Measure	Ketamine n=62 Participants Subjects in the ketamine arm will receive ketamine for sedation prior to rapid sequence intubation (RSI). Ketamine: Subjects will receive ketamine for sedation prior to rapid sequence intubation.	Etomidate n=67 Participants Subjects in the etomidate arm will receive etomidate for sedation prior to rapid sequence intubation (RSI). Etomidate: Subjects will receive etomidate for sedation prior to rapid sequence intubation.	Total n=129 Participants Total of all reporting groups
Age, Continuous	49 years STANDARD_DEVIATION 20 • n=5 Participants	49 years STANDARD_DEVIATION 19 • n=7 Participants	49 years STANDARD_DEVIATION 19 • n=5 Participants
Sex: Female, Male Female	25 Participants n=5 Participants	23 Participants n=7 Participants	48 Participants n=5 Participants
Sex: Female, Male Male	37 Participants n=5 Participants	44 Participants n=7 Participants	81 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	18 Participants n=5 Participants	18 Participants n=7 Participants	36 Participants n=5 Participants
Race (NIH/OMB) White	38 Participants n=5 Participants	37 Participants n=7 Participants	75 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	7 Participants n=7 Participants	7 Participants n=5 Participants

PRIMARY outcome

Timeframe: up to 3 days

*Maximum SOFA score within three hospital days: all patients. SOFA score is the Sequential Organ Failure Assessment. The minimum score is 0, the maximum score is 24, with higher scores indicating higher likelihood of worse outcome.

Outcome measures

Measure	Ketamine n=62 Participants Subjects in the ketamine arm will receive ketamine for sedation prior to rapid sequence intubation (RSI). Ketamine: Subjects will receive ketamine for sedation prior to rapid sequence intubation.	Etomidate n=67 Participants Subjects in the etomidate arm will receive etomidate for sedation prior to rapid sequence intubation (RSI). Etomidate: Subjects will receive etomidate for sedation prior to rapid sequence intubation.
SOFA Score	6.5 units on a scale Interval 5.0 to 9.0	7 units on a scale Interval 5.0 to 9.0

SECONDARY outcome

Timeframe: 30 Days

Population: Subgroup of those with sepsis

Evaluate mortality for the sub-group diagnosed with sepsis and septic shock, defined as:

• Suspected infection, and at least 2 of 4 systemic inflammatory response syndrome (SIRS) criteria:

1. Temperature >38C or <36C

2. Respiratory Rate >20 or PaCO2 <32 mmHg

3. Heart Rate >90

4. White blood cell count >12,000 or <4,000, or > 10% bands

Septic shock:

defined as sepsis plus either: 1) Systolic blood pressure <90 after 1L of intravenous fluid or 2) lactate >=4mmol/L

Outcome measures

Measure	Ketamine n=9 Participants Subjects in the ketamine arm will receive ketamine for sedation prior to rapid sequence intubation (RSI). Ketamine: Subjects will receive ketamine for sedation prior to rapid sequence intubation.	Etomidate n=16 Participants Subjects in the etomidate arm will receive etomidate for sedation prior to rapid sequence intubation (RSI). Etomidate: Subjects will receive etomidate for sedation prior to rapid sequence intubation.
Mortality in Sepsis and Septic Shock	1 Participants	4 Participants

SECONDARY outcome

Timeframe: up to 5 minutes (average time frame)

The rate of first pass success, defined as successful tracheal intubation on the first attempt. An attempt is defined as the insertion and subsequent removal of the laryngoscopic device from the patient's mouth, regardless of whether an endotracheal tube was inserted.

Outcome measures

Measure	Ketamine n=62 Participants Subjects in the ketamine arm will receive ketamine for sedation prior to rapid sequence intubation (RSI). Ketamine: Subjects will receive ketamine for sedation prior to rapid sequence intubation.	Etomidate n=67 Participants Subjects in the etomidate arm will receive etomidate for sedation prior to rapid sequence intubation (RSI). Etomidate: Subjects will receive etomidate for sedation prior to rapid sequence intubation.
Number of Patients With First-pass Success	59 Participants	60 Participants

SECONDARY outcome

Timeframe: up to 6 hours

The number of bolus doses of sedative administered post-intubation will be compared up to 6 hours (including morphine, dexmedetomidine, propofol , etomidate, ketamine, lorazepam (Ativan), midazolam (Versed), diazepam (Valium), fentanyl, hydromorphone (Dilaudid)). Infusions of these medications will be recorded separately but will not be part of this outcome.

Outcome measures

Measure	Ketamine n=62 Participants Subjects in the ketamine arm will receive ketamine for sedation prior to rapid sequence intubation (RSI). Ketamine: Subjects will receive ketamine for sedation prior to rapid sequence intubation.	Etomidate n=67 Participants Subjects in the etomidate arm will receive etomidate for sedation prior to rapid sequence intubation (RSI). Etomidate: Subjects will receive etomidate for sedation prior to rapid sequence intubation.
Doses of Post-intubation Sedation	1 bolus doses of sedation Interval 0.0 to 2.0	1 bolus doses of sedation Interval 0.0 to 2.0

SECONDARY outcome

Timeframe: up to 2 hours

Population: Those with oxygen saturation data

The following will be compared between the two groups:

• Hypoxemia and severe hypoxemia in the peri-intubation period. Peri-intubation hypoxemia was defined as during after the 5 minutes immediately after intubation.
• Hypoxemia within the first 2 hours intubation

Hypoxemia is defined as SpO2 less than 90%. Severe hypoxemia is defined as SpO2 less than 90% for 60 seconds or more.

Outcome measures

Measure	Ketamine n=59 Participants Subjects in the ketamine arm will receive ketamine for sedation prior to rapid sequence intubation (RSI). Ketamine: Subjects will receive ketamine for sedation prior to rapid sequence intubation.	Etomidate n=66 Participants Subjects in the etomidate arm will receive etomidate for sedation prior to rapid sequence intubation (RSI). Etomidate: Subjects will receive etomidate for sedation prior to rapid sequence intubation.
Number of Patients With Post-intubation Hypoxemia Peri-intubation hypoxemia	8 Participants	13 Participants
Number of Patients With Post-intubation Hypoxemia Hypoxemia within 2 h of ICU admission	1 Participants	5 Participants

SECONDARY outcome

Timeframe: up to 6 hours

The following will be compared between the two groups:

• Hypotension in the ED post-intubation
• Hypotension within the first 6 hours of the hospital stay, including time spent in the ED

Hypotension is defined as a systolic blood pressure less than 90 mm Hg

Outcome measures

Measure	Ketamine n=62 Participants Subjects in the ketamine arm will receive ketamine for sedation prior to rapid sequence intubation (RSI). Ketamine: Subjects will receive ketamine for sedation prior to rapid sequence intubation.	Etomidate n=67 Participants Subjects in the etomidate arm will receive etomidate for sedation prior to rapid sequence intubation (RSI). Etomidate: Subjects will receive etomidate for sedation prior to rapid sequence intubation.
Number of Patients With Hypotension Hypotension in the first 6 hours of hospitalizatio	24 Participants	30 Participants
Number of Patients With Hypotension Hypotension in the ED	16 Participants	17 Participants

SECONDARY outcome

Timeframe: up to 30 minutes (average time frame)

Population: Those with peak and plateau pressure available

The Peak and plateau pressures will be compared between the two groups, with a pre-defined subgroup analysis of patients who are being intubated for severe asthma and chronic obstructive pulmonary disease (COPD). The ventilator was used to measure these values.

Outcome measures

Measure	Ketamine n=60 Participants Subjects in the ketamine arm will receive ketamine for sedation prior to rapid sequence intubation (RSI). Ketamine: Subjects will receive ketamine for sedation prior to rapid sequence intubation.	Etomidate n=65 Participants Subjects in the etomidate arm will receive etomidate for sedation prior to rapid sequence intubation (RSI). Etomidate: Subjects will receive etomidate for sedation prior to rapid sequence intubation.
Peak and Plateau Pressure Plateau Pressure	16 cm water Interval 14.0 to 20.0	17 cm water Interval 16.0 to 20.0
Peak and Plateau Pressure Peak pressure	25 cm water Interval 23.0 to 30.0	26 cm water Interval 22.0 to 31.0

SECONDARY outcome

Timeframe: 30 Days or Discharge

Mortality will be assessed at 30 days or at discharge from the hospital, whichever occurs first. This study is not powered to detect a significant difference in mortality, however; this will primarily be a safety study comparing the use ketamine versus etomidate as sedative agents for rapid sequence intubation (RSI) in the Emergency Department (ED).

Outcome measures

Measure	Ketamine n=62 Participants Subjects in the ketamine arm will receive ketamine for sedation prior to rapid sequence intubation (RSI). Ketamine: Subjects will receive ketamine for sedation prior to rapid sequence intubation.	Etomidate n=67 Participants Subjects in the etomidate arm will receive etomidate for sedation prior to rapid sequence intubation (RSI). Etomidate: Subjects will receive etomidate for sedation prior to rapid sequence intubation.
Mortality	8 Participants	15 Participants

Adverse Events

Ketamine

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Etomidate

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Ketamine n=62 participants at risk Subjects in the ketamine arm will receive ketamine for sedation prior to rapid sequence intubation (RSI). Ketamine: Subjects will receive ketamine for sedation prior to rapid sequence intubation.	Etomidate n=67 participants at risk Subjects in the etomidate arm will receive etomidate for sedation prior to rapid sequence intubation (RSI). Etomidate: Subjects will receive etomidate for sedation prior to rapid sequence intubation.
Cardiac disorders Severe hypertension	1.6% 1/62 • Number of events 1	0.00% 0/67

Other adverse events

Adverse event data not reported

Additional Information

Audrey Hendrickson

Hennepin Healthcare

Phone: 612-873-9528

Email: Audrey.Hendrickson@hcmed.org

Results disclosure agreements

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