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

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ClinicalTrials.gov Identifier: NCT03009409
Recruitment Status : Completed
First Posted : January 4, 2017
Last Update Posted : May 6, 2019
Sponsor:
Collaborators:
Fraser Health
Office of Naval Research (ONR)
Information provided by (Responsible Party):
NeuroWave Systems Inc.

Tracking Information
First Submitted Date  ICMJE December 29, 2016
First Posted Date  ICMJE January 4, 2017
Last Update Posted Date May 6, 2019
Actual Study Start Date  ICMJE March 13, 2018
Actual Primary Completion Date October 17, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 30, 2016)
Controller performance [ Time Frame: Through study completion, an average of 1 year ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 30, 2016)
  • Vital signs [ Time Frame: Through study completion, an average of 1 year ]
    In the OR, the investigators will record other indications of anesthetic quality, such as vital signs and the occurrence of any unwanted intra-operative events. Propofol and remifentanil consumption will be quantified, and the requirement of any other interventions will be recorded. The investigators will also record post-operative patient outcomes that have previously been associated with ketamine administration, such as acute post-operative pain intensity, opioid requirements, the occurrence of PONV, and shivering occurring in the post-anesthesia care unit (PACU). Analysis of group differences in secondary intra-operative and post-operative measures will be mainly exploratory, as this study was not designed to detect a definitive difference between these variables. Rather, these data may contribute to a developing body of evidence elucidating the potential benefits of low dose ketamine. Any outliers will be described and discussed on a case-by-base / incidence basis.
  • Number of unwanted intra-operative events [ Time Frame: Through study completion, an average of 1 year ]
    In the OR, the investigators will record other indications of anesthetic quality, such as vital signs and the occurrence of any unwanted intra-operative events. Propofol and remifentanil consumption will be quantified, and the requirement of any other interventions will be recorded. The investigators will also record post-operative patient outcomes that have previously been associated with ketamine administration, such as acute post-operative pain intensity, opioid requirements, the occurrence of PONV, and shivering occurring in the post-anesthesia care unit (PACU). Analysis of group differences in secondary intra-operative and post-operative measures will be mainly exploratory, as this study was not designed to detect a definitive difference between these variables. Rather, these data may contribute to a developing body of evidence elucidating the potential benefits of low dose ketamine. Any outliers will be described and discussed on a case-by-base / incidence basis.
  • Propofol consumption [ Time Frame: Through study completion, an average of 1 year ]
    In the OR, the investigators will record other indications of anesthetic quality, such as vital signs and the occurrence of any unwanted intra-operative events. Propofol and remifentanil consumption will be quantified, and the requirement of any other interventions will be recorded. The investigators will also record post-operative patient outcomes that have previously been associated with ketamine administration, such as acute post-operative pain intensity, opioid requirements, the occurrence of PONV, and shivering occurring in the post-anesthesia care unit (PACU). Analysis of group differences in secondary intra-operative and post-operative measures will be mainly exploratory, as this study was not designed to detect a definitive difference between these variables. Rather, these data may contribute to a developing body of evidence elucidating the potential benefits of low dose ketamine. Any outliers will be described and discussed on a case-by-base / incidence basis.
  • Remifentanil consumption [ Time Frame: Through study completion, an average of 1 year ]
    In the OR, the investigators will record other indications of anesthetic quality, such as vital signs and the occurrence of any unwanted intra-operative events. Propofol and remifentanil consumption will be quantified, and the requirement of any other interventions will be recorded. The investigators will also record post-operative patient outcomes that have previously been associated with ketamine administration, such as acute post-operative pain intensity, opioid requirements, the occurrence of PONV, and shivering occurring in the post-anesthesia care unit (PACU). Analysis of group differences in secondary intra-operative and post-operative measures will be mainly exploratory, as this study was not designed to detect a definitive difference between these variables. Rather, these data may contribute to a developing body of evidence elucidating the potential benefits of low dose ketamine. Any outliers will be described and discussed on a case-by-base / incidence basis.
  • Post-operative pain intensity [ Time Frame: Through study completion, an average of 1 year ]
    In the OR, the investigators will record other indications of anesthetic quality, such as vital signs and the occurrence of any unwanted intra-operative events. Propofol and remifentanil consumption will be quantified, and the requirement of any other interventions will be recorded. The investigators will also record post-operative patient outcomes that have previously been associated with ketamine administration, such as acute post-operative pain intensity, opioid requirements, the occurrence of PONV, and shivering occurring in the post-anesthesia care unit (PACU). Analysis of group differences in secondary intra-operative and post-operative measures will be mainly exploratory, as this study was not designed to detect a definitive difference between these variables. Rather, these data may contribute to a developing body of evidence elucidating the potential benefits of low dose ketamine. Any outliers will be described and discussed on a case-by-base / incidence basis.
  • Number of participants experiencing PONV [ Time Frame: Through study completion, an average of 1 year ]
    In the OR, the investigators will record other indications of anesthetic quality, such as vital signs and the occurrence of any unwanted intra-operative events. Propofol and remifentanil consumption will be quantified, and the requirement of any other interventions will be recorded. The investigators will also record post-operative patient outcomes that have previously been associated with ketamine administration, such as acute post-operative pain intensity, opioid requirements, the occurrence of PONV, and shivering occurring in the post-anesthesia care unit (PACU). Analysis of group differences in secondary intra-operative and post-operative measures will be mainly exploratory, as this study was not designed to detect a definitive difference between these variables. Rather, these data may contribute to a developing body of evidence elucidating the potential benefits of low dose ketamine. Any outliers will be described and discussed on a case-by-base / incidence basis.
  • Number of participants experiencing shivering in PACU [ Time Frame: Through study completion, an average of 1 year ]
    In the OR, the investigators will record other indications of anesthetic quality, such as vital signs and the occurrence of any unwanted intra-operative events. Propofol and remifentanil consumption will be quantified, and the requirement of any other interventions will be recorded. The investigators will also record post-operative patient outcomes that have previously been associated with ketamine administration, such as acute post-operative pain intensity, opioid requirements, the occurrence of PONV, and shivering occurring in the post-anesthesia care unit (PACU). Analysis of group differences in secondary intra-operative and post-operative measures will be mainly exploratory, as this study was not designed to detect a definitive difference between these variables. Rather, these data may contribute to a developing body of evidence elucidating the potential benefits of low dose ketamine. Any outliers will be described and discussed on a case-by-base / incidence basis.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Effect of Low Dose Intra-operative Ketamine on Closed-loop Controlled General Anesthesia
Official Title  ICMJE The Effect of Low Dose Intra-operative Ketamine on Closed-loop Controlled General Anesthesia
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.

Detailed Description

For the primary outcome measure, the investigators hypothesize that controller performance with low-dose ketamine will be equivalent to the controller performance without low-dose ketamine. The primary outcome measure, controller performance, is the percentage of time during the maintenance phase when the depth-of-hypnosis (DOH) measure is within +-10 points of the set point in patients receiving low dose ketamine versus those receiving saline control.

This study will consider other clinical data of interest from both intra- and post-operative contexts in order to establish a broader understanding of the potential implications of the use of a low dose of ketamine during closed-loop controlled anesthesia. In the OR, the investigators will record other indications of anesthetic quality, such as vital signs and the occurrence of any unwanted intra-operative events. Propofol and remifentanil consumption will be quantified, and the requirement of any other interventions will be recorded. The investigators will also record post-operative patient outcomes that have previously been associated with ketamine administration, such as acute post-operative pain intensity, opioid requirements, the occurrence of PONV, and shivering occurring in the post-anesthesia care unit (PACU).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Other
Condition  ICMJE Anesthesia
Intervention  ICMJE
  • Drug: Ketamine Injectable Solution

    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.

  • Other: Placebo
    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.
Study Arms  ICMJE
  • Active Comparator: Ketamine Group
    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.
    Intervention: Drug: Ketamine Injectable Solution
  • Placebo Comparator: Control Group
    Participants in the control group will receive an equivalent volume bolus and infusion of normal saline to mimic the ketamine infusion.
    Intervention: Other: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 30, 2016)
60
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE October 17, 2018
Actual Primary Completion Date October 17, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 19 Years to 54 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03009409
Other Study ID Numbers  ICMJE 925-0702-DCI
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party NeuroWave Systems Inc.
Study Sponsor  ICMJE NeuroWave Systems Inc.
Collaborators  ICMJE
  • Fraser Health
  • Office of Naval Research (ONR)
Investigators  ICMJE
Principal Investigator: Richard Merchant, MD FRCPC Fraser Health
PRS Account NeuroWave Systems Inc.
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP