Perioperative Ketamine in Opioid-Tolerant Patients Undergoing Lumbar Spine Surgery

NCT04220489 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: STUDY19020144
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to determine whether comprehensive perioperative administration of the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine can increase postoperative pain tolerance and reduce opiate consumption in chronic back pain patients undergoing spinal laminectomy/fusion when compared to placebo Opioid dependence will be defined as daily opioid use (2 or more doses per day) for a period of two-months or longer. Intraoperatively, patients will receive a 1 mg/kg dose of intravenous ketamine or saline with 15 minutes after induction of general anesthesia. Thereafter, a continuous infusion of 0.20 mg/kg/hr ketamine with a maximum dose of 20 mg/hr or saline will be run to conclude at 24 hours after the end of the surgery (fascial closure). The primary outcome measure will be hydromorphone PCA usage during the first 72 hours postoperatively. Secondary outcome measures will be VAS pain scores at rest and with movement in PACU, 24 hr, 48 hr, 72 hr, 2 week (post-op visit), 6 week follow-up visit, as well as, McGill Pain Questionnaire, Pain Catastrophizing Scale, and emotional distress surveys assessing depression and anxiety at preop/screening, postop and 6 week follow-up (PROMIS Emotional Distress-Anxiety Short Form, PROMIS Emotional Distress-Depression Short Form), as well as a Neuro-QOL Short Form v1.1 - Satisfaction with Social Roles and Activities .

Conditions

Opioid Dependence; Chronic Pain

Keywords

Ketamine; Lumbar Spine Surgery; Opioid Tolerant

Outcome Measures

Primary Outcomes (6)

• Post-surgical Hydromorphone Patient Care Assistance (PCA) Opioid Utilization

  Hydromorphone Patient Care Assistant (PCA) usage during the first 72 hours postoperatively will be recorded. Hydromorphone opioid usage will be assessed and converted to morphine equivalents/24 hour. The higher the values, the worse the outcomes.

  72 hours postoperatively

• Post-surgical Pain Rating Using the Visual Analog Scale (VAS)

  Post-surgical pain ratings will be measured by the assessment of participant's answers to the Visual Analog Scale (VAS). This measurement is a visual scale from 0-10, 0 being no pain, 5 being moderate pain and 10 being the worst imaginable pain. The lowest possible score is 0 and the highest possible score is 10. The participant will be asked to score pain at its best and worst over the period since they were last asked. Higher scores present a worse outcome. Pain will be monitored every four hours from the time the participant enters the PACU until discharge from the hospital, except during the night when the participant is asleep. The value reported consists of the average of all pain scores collected.

  72 hours post-operatively

• Post-surgical Opioid Utilization Using Electronic Medication Review

  Post-surgical opioid utilization will be measured by reviewing participant's electronic medical records and recording opioid usage. Daily opioid usage will be assessed and converted to morphine equivalents/24 hr. The higher the values, the worse the outcomes.

  72 hours post-operatively

• Post-surgical Opioid Utilization Using Electronic Medication Review

  Post-surgical opioid utilization will be measured by reviewing participant's electronic medical records and recording opioid usage. Daily opioid usage will be assessed and converted to morphine equivalents/24 hr. The higher the values, the worse the outcomes.

  6-week follow-up visit

• Pre-surgical Opioid Utilization Using the Pain Medication Review Form

  Pre-surgical opioid utilization will be measured by the Pain Medication Review Form where patients will record all of the medications they are currently taking.

  Screening visit

• Pre-surgical Pain Rating Using the Visual Analog Scale (VAS)

  Post-surgical pain ratings will be measured by the assessment of participant's answers to the Visual Analog Scale (VAS). This measurement is a visual scale from 0-10, 0 being no pain, 5 being moderate pain and 10 being the worst imaginable pain. The lowest possible score is 0 and the highest possible score is 10. Higher scores present a worse outcome.

  Screening visit

Secondary Outcomes (14)

• Pre-surgical Emotional Distress Related to Depression

  Screening visit

• Post-surgical Emotional Distress Related to Depression

  Day 10-14 Post-Operative Visit

• Post-surgical Emotional Distress Related to Depression

  6-week follow-up visit

• Pre-surgical Emotional Distress Related to Anxiety

  Screening visit

• Post-surgical Emotional Distress Related to Anxiety

  Day 10-14 Post-Operative Visit

Study Arms (2)

Ketamine Group

EXPERIMENTAL

Participants will receive a 1 mg/kg dose of intravenous ketamine 15 minutes after induction of general anesthesia. Thereafter, a continuous infusion of 0.20 mg/kg/hr ketamine with a maximum dose of 20 mg/hr will be run to conclude at 48 hours after the end of the surgery (fascial closure).

Drug: Ketamine

Placebo Group

PLACEBO COMPARATOR

Participants will receive a 1 mg/kg dose of intravenous saline 15 minutes after induction of general anesthesia. Thereafter, a continuous infusion of 0.20 mg/kg/hr saline with a maximum dose of 20 mg/hr will be run to conclude at 48 hours after the end of the surgery (fascial closure).

Drug: Placebo Comparator

Interventions

Ketamine DRUG

Intraoperative ketamine and post operative 48 hour ketamine infusion with a standardized general anesthesia protocol.

Also known as: Ketalar

Ketamine Group

Placebo Comparator DRUG

Participants will receive a 1 mg/kg dose of intravenous saline 15 minutes after induction of general anesthesia. Thereafter, a continuous infusion of 0.20 mg/kg/hr saline with a maximum dose of 20 mg/hr will be run to conclude at 48 hours after the end of the surgery (fascial closure)

Also known as: Placebo Group

Placebo Group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients undergoing lumbar, thoracic or cervical spine surgery of at least one level, and no more than 6 levels.
• Patients with chronic back pain (\>3 months)
• Anaesthetic risk assessment (ASA) 1-3
• Opiate-dependent with daily opiate use for at least 2 months and regimented daily narcotic dose twice a day/bis in die (BID) or greater or use of a regimented opioid pump

You may not qualify if:

• Intolerance or known allergy to ketamine
• History of increased intraocular pressure (\> 22mmHg)
• Uncontrolled hypertension (systolic blood pressure greater than or equal to 180, diastolic blood pressure greater than equal to 100)
• Increased intracranial pressure
• History of psychosis
• Pregnancy
• Patients with significant liver disease {signs and symptoms of liver injury, such as discolored skin and eyes that appear yellowish, abdominal pain and swelling, Itchy skin that doesn't seem to go away, dark urine color, pale stool color, bloody or tar-colored stool, chronic fatigue, nausea, loss of appetite, with or without elevated Liver Function Tests (LFTs): aspartate aminotransferase (AST) \> 120 IU/ml, alkaline phosphatase (AP) \>130 IU/ml, and alanine aminotransferase (ALT) \>40 IU/ml}
• Patients with exposure to Cytochrome P450, family 3, subfamily A (CYP3A) and / or Cytochrome P450 Family 2 Subfamily B Member 6 (CYP2B6) inhibitors, including the herbs and the over-the-counter compounds (list of drugs can be found at http://www.fda.gov/drugs/developmentapprovalprocess/developmentresources/druginteractionslabeling/ucm093664.htm)

Sponsors & Collaborators

• Jacques E. Chelly: lead

Study Sites (1)

Jacques E Chelly, MD

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Opioid-Related Disorders; Chronic Pain

Interventions

Ketamine

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Jacques E. Chelly, MD, PhD, MBA
• Organization: UPMC

chelje@anes.upmc.edu

412-623-6904

Study Officials

• Jacques E Chelly, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Anesthesiology and Perioperative Medicine and Orthopedic Surgery Director, Regional Anesthesiology Fellowship Program

Model Details: Prospective, Randomized, Double-Blind, Placebo Controlled trial involving opiate-dependent patients undergoing lumbar spine surgery

Study Record Dates

• First Submitted: November 21, 2019
• First Posted: January 7, 2020
• Study Start: December 17, 2019
• Primary Completion: November 19, 2022
• Study Completion: November 19, 2022
• Last Updated: January 30, 2024
• Results First Posted: January 30, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)