The Effect of Low Dose Intra-operative Ketamine on Closed-loop Controlled General Anesthesia

NCT03009409 | Completed Phase 1

• 1 other identifier: 925-0702-DCI
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Closed-loop control of anesthesia involves using feedback from a measure of clinical effect to continuously adjust drug infusion rates. As a result, anesthetic drugs are delivered at a variable rate that is frequently personalized to each individual patient. The aim is to provide greater stability at an optimal depth of anesthesia, reducing the occurrence of under- or overdosing, with the goal of ultimately improving patient outcomes. The purpose of this randomized, controlled equivalence trial is to compare controller performance during closed-loop controlled induction and maintenance of total intravenous anesthesia, using iControl system, with the addition of a low (analgesic) dose of ketamine versus saline control.

Conditions

Anesthesia

Outcome Measures

Primary Outcomes (1)

• Controller performance

  The primary outcome measure for this equivalence trial is 'controller performance', calculated as the percentage of time during the maintenance phase when the depth-of-hypnosis (DOH) measure is within ±10 points of the set point.

  Through study completion, an average of 1 year

Secondary Outcomes (7)

• Vital signs

  Through study completion, an average of 1 year

• Number of unwanted intra-operative events

  Through study completion, an average of 1 year

• Propofol consumption

  Through study completion, an average of 1 year

• Remifentanil consumption

  Through study completion, an average of 1 year

• Post-operative pain intensity

  Through study completion, an average of 1 year

Study Arms (2)

Ketamine Group

ACTIVE COMPARATOR

Participants randomized to the ketamine group will receive a 0.25 mg/kg loading dose of intravenous ketamine immediately before induction of anesthesia, followed by a continuous 5 mcg/kg/min infusion throughout maintenance of anesthesia, for approximately 45 minutes, up to a maximum cumulative dose of 100 mg. This dose is in accordance with the guidelines from the recently published Clinical Practice Guidelines for the management of post-operative pain. The attending anesthesiologist will confirm whether the use of ketamine is appropriate for each patient prior to enrolling the patient in the study.

Drug: Ketamine Injectable Solution

Control Group

PLACEBO COMPARATOR

Participants in the control group will receive an equivalent volume bolus and infusion of normal saline to mimic the ketamine infusion.

Other: Placebo

Interventions

Ketamine Injectable Solution DRUG

Once IV access has been obtained and a facemask has been applied for pre-oxygenation, the loading dose (0.25 mg/kg) of the study drug will be given over 60 seconds and the fixed infusion (5 mcg/kg/min to a maximum of 60 mg/hour) will be initiated by the anesthetist through the pump interface. The study drug will be infused at a constant rate of 5 mcg/kg/min throughout the maintenance phase, until the end of the procedure (last suture), up to a maximum cumulative dose of 100 mg. If at any point the anesthesiologist feels that it is clinically necessary to reduce the amount of study drug infusion rate, they may opt to reduce the infusion rate by 50% (to 2.5 mcg/kg/min), or stop the infusion entirely.

Ketamine Group

Placebo OTHER

Participants in the control group will receive an equivalent volume bolus and infusion of normal saline to mimic the ketamine infusion in the ketamine group.

Control Group

Eligibility Criteria

• Age: 19 Years - 54 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age 19-54
• ASA I-II
• BMI 15-45
• Elective ACL repair surgery requiring general anesthesia
• Ability to read and understand the informed consent form

You may not qualify if:

• Contraindications to ketamine use Those in whom a significant elevation of blood pressure would constitute a serious hazard (e.g. severe cardiovascular disease, pacemaker, pheochromocytoma, malignant hypertension, intraocular pressure pathology, acute globe injury, hyperthyroidism)
• Contraindications to propofol Anaphylactic reaction to eggs, egg products, soybeans or soy products
• Contraindications to remifentanil Hypersensitivity to fentanyl analogues
• Known or suspected neurological disease Tumor, stroke, neurodegenerative disease, major head injury, seizure disorder Abnormality in any previous EEG examination Cognitive deficits (e.g. dementia, developmental delay)
• Acquired scalp or skull abnormalities
• Psychiatric illness Severe depression, PTSD, psychosis Any psychotropic medication taken in the past 7 days
• History of drug misuse/abuse within past 30 days Ketamine, cocaine, heroin, amphetamines, phencyclindine, lysergic acid (LSD), mescaline, psilocybin Chronic alcoholism
• Requirement for pre-operative sedative medication (e.g. midazolam) for anxiolysis
• Anticipated intra-operative or pre-operative use of nitrous oxide, catecholamines (dopamine, epinephrine, norepinephrine) or thyroid hormones
• Pregnant or nursing
• Currently enrolled in any other research study involving drugs or devices

Sponsors & Collaborators

• NeuroWave Systems Inc.: lead
• Fraser Health: collaborator
• Office of Naval Research (ONR): collaborator

Study Sites (1)

Fraser Health: Eagle Ridge Hospital

Port Moody, British Columbia, V3H 3W9, Canada

Location

Study Officials

• Richard Merchant, MD FRCPC

  Fraser Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 29, 2016
• First Posted: January 4, 2017
• Study Start: March 13, 2018
• Primary Completion: October 17, 2018
• Study Completion: October 17, 2018
• Last Updated: May 6, 2019

Record last verified: 2019-05

Locations

CA (1)