Trial Outcomes & Findings for The Impact of Perioperative Ketamine Infusion on Surgical Recovery (NCT NCT04625283)

NCT ID: NCT04625283

Last Updated: 2025-02-04

Results Overview

The participants length of stay, from anesthesia beginning to discharge, measured in days

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 1570 participants
• Primary outcome timeframe: From surgery start until discharge, typically 3-5 days
• Results posted on: 2025-02-04

Participant Flow

Participant milestones

Measure	Ketamine Participants in this arm will receive intraoperative ketamine bolus (0.5mg/kg) followed by continuous infusion 5 mcg/kg/min and also will receive postoperative ketamine infusion (2.5 mcg/kg/min, up to 100kg max) for 48 hours. Ketamine: Participants in the ketamine arm will receive intraoperative and postoperative ketamine.	Saline Participants in this arm will receive an equivalent volume of intraoperative saline bolus followed by continuous saline infusion and also will receive postoperative saline infusion for 48 hours. Placebo: Participants in the placebo arm will receive intraoperative and postoperative saline.
Overall Study STARTED	798	772
Overall Study COMPLETED	770	752
Overall Study NOT COMPLETED	28	20

Reasons for withdrawal

Measure	Ketamine Participants in this arm will receive intraoperative ketamine bolus (0.5mg/kg) followed by continuous infusion 5 mcg/kg/min and also will receive postoperative ketamine infusion (2.5 mcg/kg/min, up to 100kg max) for 48 hours. Ketamine: Participants in the ketamine arm will receive intraoperative and postoperative ketamine.	Saline Participants in this arm will receive an equivalent volume of intraoperative saline bolus followed by continuous saline infusion and also will receive postoperative saline infusion for 48 hours. Placebo: Participants in the placebo arm will receive intraoperative and postoperative saline.
Overall Study post randomization exclusion	28	20

Baseline Characteristics

The Impact of Perioperative Ketamine Infusion on Surgical Recovery

Baseline characteristics by cohort

Measure	Ketamine n=770 Participants Participants in this arm will receive intraoperative ketamine bolus (0.5mg/kg) followed by continuous infusion 5 mcg/kg/min and also will receive postoperative ketamine infusion (2.5 mcg/kg/min, up to 100kg max) for 48 hours. Ketamine: Participants in the ketamine arm will receive intraoperative and postoperative ketamine.	Saline n=752 Participants Participants in this arm will receive an equivalent volume of intraoperative saline bolus followed by continuous saline infusion and also will receive postoperative saline infusion for 48 hours. Placebo: Participants in the placebo arm will receive intraoperative and postoperative saline.	Total n=1522 Participants Total of all reporting groups
Age, Continuous	58.9 years n=5 Participants	57.8 years n=7 Participants	58.3 years n=5 Participants
Sex: Female, Male Female	371 Participants n=5 Participants	380 Participants n=7 Participants	751 Participants n=5 Participants
Sex: Female, Male Male	399 Participants n=5 Participants	372 Participants n=7 Participants	771 Participants n=5 Participants
Race/Ethnicity, Customized White	686 Participants n=5 Participants	660 Participants n=7 Participants	1346 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	58 Participants n=5 Participants	67 Participants n=7 Participants	125 Participants n=5 Participants
Race/Ethnicity, Customized Asian	3 Participants n=5 Participants	11 Participants n=7 Participants	14 Participants n=5 Participants
Race/Ethnicity, Customized Other	15 Participants n=5 Participants	9 Participants n=7 Participants	24 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic/Latino	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	5 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants
Region of Enrollment United States	770 Participants n=5 Participants	752 Participants n=7 Participants	1522 Participants n=5 Participants
Opioid status Exposed	82 Participants n=5 Participants	76 Participants n=7 Participants	158 Participants n=5 Participants
Opioid status Naive	688 Participants n=5 Participants	676 Participants n=7 Participants	1364 Participants n=5 Participants
BMI (kg/m²)	27.3 kg/m² n=5 Participants	27.6 kg/m² n=7 Participants	27.4 kg/m² n=5 Participants

PRIMARY outcome

Timeframe: From surgery start until discharge, typically 3-5 days

The participants length of stay, from anesthesia beginning to discharge, measured in days

Outcome measures

Measure	Ketamine n=770 Participants Participants in this arm will receive intraoperative ketamine bolus (0.5mg/kg) followed by continuous infusion 5 mcg/kg/min and also will receive postoperative ketamine infusion (2.5 mcg/kg/min, up to 100kg max) for 48 hours. Ketamine: Participants in the ketamine arm will receive intraoperative and postoperative ketamine.	Saline n=752 Participants Participants in this arm will receive an equivalent volume of intraoperative saline bolus followed by continuous saline infusion and also will receive postoperative saline infusion for 48 hours. Placebo: Participants in the placebo arm will receive intraoperative and postoperative saline.
Length of Stay	5.0 days Interval 4.0 to 8.0	5.0 days Interval 3.0 to 7.2

SECONDARY outcome

Timeframe: From hospital admission until discharge, typically 3-5 days

Inpatient opioid consumption measured in morphine milligram equivalents

Outcome measures

Measure	Ketamine n=770 Participants Participants in this arm will receive intraoperative ketamine bolus (0.5mg/kg) followed by continuous infusion 5 mcg/kg/min and also will receive postoperative ketamine infusion (2.5 mcg/kg/min, up to 100kg max) for 48 hours. Ketamine: Participants in the ketamine arm will receive intraoperative and postoperative ketamine.	Saline n=752 Participants Participants in this arm will receive an equivalent volume of intraoperative saline bolus followed by continuous saline infusion and also will receive postoperative saline infusion for 48 hours. Placebo: Participants in the placebo arm will receive intraoperative and postoperative saline.
Total Consumption of Inpatient Opioids	82.5 MME Interval 37.5 to 158.0	90.0 MME Interval 45.0 to 158.0

SECONDARY outcome

Timeframe: From hospital admission until discharge, typically 3-5 days

Number of participants reporting ileus requiring gastric decompression as defined by orogastric or nasogastric tube placement in the postoperative period.

Outcome measures

Measure	Ketamine n=770 Participants Participants in this arm will receive intraoperative ketamine bolus (0.5mg/kg) followed by continuous infusion 5 mcg/kg/min and also will receive postoperative ketamine infusion (2.5 mcg/kg/min, up to 100kg max) for 48 hours. Ketamine: Participants in the ketamine arm will receive intraoperative and postoperative ketamine.	Saline n=752 Participants Participants in this arm will receive an equivalent volume of intraoperative saline bolus followed by continuous saline infusion and also will receive postoperative saline infusion for 48 hours. Placebo: Participants in the placebo arm will receive intraoperative and postoperative saline.
Number of Participants With Ileus	71 Participants	37 Participants

SECONDARY outcome

Timeframe: From hospital admission until discharge, typically 3-5 days

Number of participants who encounter rapid response team activation within 72 hours post-operation. This is as a binary outcome

Outcome measures

Measure	Ketamine n=770 Participants Participants in this arm will receive intraoperative ketamine bolus (0.5mg/kg) followed by continuous infusion 5 mcg/kg/min and also will receive postoperative ketamine infusion (2.5 mcg/kg/min, up to 100kg max) for 48 hours. Ketamine: Participants in the ketamine arm will receive intraoperative and postoperative ketamine.	Saline n=752 Participants Participants in this arm will receive an equivalent volume of intraoperative saline bolus followed by continuous saline infusion and also will receive postoperative saline infusion for 48 hours. Placebo: Participants in the placebo arm will receive intraoperative and postoperative saline.
Number of Participants Who Encounter Rapid Response Team Activation	39 Participants	26 Participants

SECONDARY outcome

Timeframe: From hospital admission until discharge, typically 3-5 days

Number of participants who experienced transfer to ICU. This is as a binary outcome

Outcome measures

Measure	Ketamine n=770 Participants Participants in this arm will receive intraoperative ketamine bolus (0.5mg/kg) followed by continuous infusion 5 mcg/kg/min and also will receive postoperative ketamine infusion (2.5 mcg/kg/min, up to 100kg max) for 48 hours. Ketamine: Participants in the ketamine arm will receive intraoperative and postoperative ketamine.	Saline n=752 Participants Participants in this arm will receive an equivalent volume of intraoperative saline bolus followed by continuous saline infusion and also will receive postoperative saline infusion for 48 hours. Placebo: Participants in the placebo arm will receive intraoperative and postoperative saline.
Number of Participants Who Experienced ICU Transfer	44 Participants	22 Participants

SECONDARY outcome

Timeframe: From hospital admission until discharge, typically 3-5 days

Total number of side effects (hallucination, sedation, lightheadedness, patient request) as adverse reactions requiring early cessation.

Outcome measures

Measure	Ketamine n=770 Participants Participants in this arm will receive intraoperative ketamine bolus (0.5mg/kg) followed by continuous infusion 5 mcg/kg/min and also will receive postoperative ketamine infusion (2.5 mcg/kg/min, up to 100kg max) for 48 hours. Ketamine: Participants in the ketamine arm will receive intraoperative and postoperative ketamine.	Saline n=752 Participants Participants in this arm will receive an equivalent volume of intraoperative saline bolus followed by continuous saline infusion and also will receive postoperative saline infusion for 48 hours. Placebo: Participants in the placebo arm will receive intraoperative and postoperative saline.
Number of Participants Who Experienced Adverse Side Effects Other Severe Side Effect	71 Participants	37 Participants
Number of Participants Who Experienced Adverse Side Effects Met Early Discharge Milestones	96 Participants	130 Participants
Number of Participants Who Experienced Adverse Side Effects Patient Preference for Mild Side Effects	83 Participants	39 Participants
Number of Participants Who Experienced Adverse Side Effects Debilitating Hallucinations	19 Participants	7 Participants
Number of Participants Who Experienced Adverse Side Effects Debilitating Dizziness	64 Participants	11 Participants
Number of Participants Who Experienced Adverse Side Effects Hemodynamic Instability	12 Participants	6 Participants

Adverse Events

Ketamine

Serious events: 0 serious events

Other events: 322 other events

Deaths: 1 deaths

Saline

Serious events: 1 serious events

Other events: 163 other events

Deaths: 0 deaths

Serious adverse events

Measure	Ketamine n=770 participants at risk Participants in this arm will receive intraoperative ketamine bolus (0.5mg/kg) followed by continuous infusion 5 mcg/kg/min and also will receive postoperative ketamine infusion (2.5 mcg/kg/min, up to 100kg max) for 48 hours. Ketamine: Participants in the ketamine arm will receive intraoperative and postoperative ketamine.	Saline n=752 participants at risk Participants in this arm will receive an equivalent volume of intraoperative saline bolus followed by continuous saline infusion and also will receive postoperative saline infusion for 48 hours. Placebo: Participants in the placebo arm will receive intraoperative and postoperative saline.
General disorders Fall	0.00% 0/770 • Monitored from enrollment to time of hospital discharge, approximately 28 days	0.13% 1/752 • Monitored from enrollment to time of hospital discharge, approximately 28 days

Other adverse events

Measure	Ketamine n=770 participants at risk Participants in this arm will receive intraoperative ketamine bolus (0.5mg/kg) followed by continuous infusion 5 mcg/kg/min and also will receive postoperative ketamine infusion (2.5 mcg/kg/min, up to 100kg max) for 48 hours. Ketamine: Participants in the ketamine arm will receive intraoperative and postoperative ketamine.	Saline n=752 participants at risk Participants in this arm will receive an equivalent volume of intraoperative saline bolus followed by continuous saline infusion and also will receive postoperative saline infusion for 48 hours. Placebo: Participants in the placebo arm will receive intraoperative and postoperative saline.
General disorders Patient Preference forMild Side Effects	10.8% 83/770 • Monitored from enrollment to time of hospital discharge, approximately 28 days	5.2% 39/752 • Monitored from enrollment to time of hospital discharge, approximately 28 days
Psychiatric disorders Debilitating Hallucinations	2.5% 19/770 • Monitored from enrollment to time of hospital discharge, approximately 28 days	0.93% 7/752 • Monitored from enrollment to time of hospital discharge, approximately 28 days
Nervous system disorders Debilitating Dizziness	8.3% 64/770 • Monitored from enrollment to time of hospital discharge, approximately 28 days	1.5% 11/752 • Monitored from enrollment to time of hospital discharge, approximately 28 days
Vascular disorders Hemodynamic Instability	1.6% 12/770 • Monitored from enrollment to time of hospital discharge, approximately 28 days	0.80% 6/752 • Monitored from enrollment to time of hospital discharge, approximately 28 days
General disorders Rapid Response Activation	5.1% 39/770 • Monitored from enrollment to time of hospital discharge, approximately 28 days	3.5% 26/752 • Monitored from enrollment to time of hospital discharge, approximately 28 days
Surgical and medical procedures Transfer to the ICU	5.7% 44/770 • Monitored from enrollment to time of hospital discharge, approximately 28 days	2.9% 22/752 • Monitored from enrollment to time of hospital discharge, approximately 28 days
Gastrointestinal disorders Ileus Requiring NG Decompression	8.2% 63/770 • Monitored from enrollment to time of hospital discharge, approximately 28 days	6.4% 48/752 • Monitored from enrollment to time of hospital discharge, approximately 28 days
General disorders Other Severe Side Effect	9.2% 71/770 • Monitored from enrollment to time of hospital discharge, approximately 28 days	4.9% 37/752 • Monitored from enrollment to time of hospital discharge, approximately 28 days

Additional Information

Dr. Britany Martin

Vanderbilt University Medical Center

Phone: +1 (615)322-8476

Email: britany.l.raymond@vumc.org

Results disclosure agreements

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