Clinical trial NCT04220489: Perioperative Ketamine in Opioid-Tolerant Patients Undergoing Lumbar Spine Surgery
Official title: Perioperative Ketamine in Opioid-Tolerant Patients Undergoing Lumbar Spine Surgery: A Randomized, Double-blind, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Opioid Dependence
Chronic Pain
Keywords: Ketamine
Lumbar Spine Surgery
Opioid Tolerant
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
First posted: 2020-01-07
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, Randomized, Double-Blind, Placebo Controlled trial involving opiate-dependent patients undergoing lumbar spine surgery
Primary purpose: TREATMENT

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 .

Detailed description: Patients will be recruited from the University of Pittsburgh Medical Center (UPMC) Neurosurgery Clinic and Operating Room Schedule. The primary surgeon will identify patients who would be eligible for inclusion, ask them if they would be interested in participating, and if so, the enrollment and consent process would be initiated. The participating neurosurgeons include Dr. Okonkwo and Dr. Hamilton, who have agreed to allow us access to their patients. Informed consent will be performed by the surgeon or the PI. Enrollment will be performed by the study coordinator and/or trained representative from the Acute Interventional Perioperative Pain Service (AIPPS). Enrollment will include review of eligibility, and detailed explanation of the study.

Screening Visit:

After patients are enrolled into the study at the preoperative neurosurgery clinic, a number of forms will be filled out by the participants: McGill Pain questionaire-Short form, pain medication review form, and the Pain Catastrophizing Scale (PCS) (Sullivan, 1995). PROMIS Emotional Distress-Anxiety Short Form and PROMIS Emotional Distress-Depression Short Form, Brief Psychiatric Rating Scale and Neuro-QoL Short Form v1.1 - Satisfaction with Social Roles and Activities will also be completed.

Pre-Operative Visit:

The participant will be asked to come into the Aiken Medical Building, Suite 407 on a date after the clinic visit but before their day of surgery for a Pre-Operative Visit. Investigators will work with the participant to determine their opioid dose regimen, and the participant will be asked to come into the Aiken Medical Building thirty minutes before their opioid dose is due and will be asked to bring with them their upcoming dose of pain medication. Prior to taking their pain medication, the participant will then be administered a cold-pressor pain sensitivity test. Heart rate and blood pressure will be recorded before and after the cold-pressor test. Once the cold pressor test is completed, the McGill Pain Questionnaire will be administered. After this questionnaire is complete, the participant will take the dose of opioid medication they have brought from home and are scheduled to receive and will wait in the clinic for 30 minutes for the pain medication to take effect. Once the 30 minutes is complete, the cold-pressor test will be repeated, heart rate and blood pressure collected before and after, and McGill Pain Questionnaire will be administered again.

Surgical Visit:

At the day of surgery, participants will be seen by team members of the Acute Interventional Perioperative Pain Service preoperatively. Patients will be randomized into the Ketamine Group or the Placebo Group.

A standardized general anesthesia protocol will be used by the hands-on provider. All drugs used intraoperatively, including total hydromorphone dose, will be collected from the electronic chart.

The amount of narcotics and non-narcotic analgesics administered in the operative and postoperative period will be collected from the electronic chart from day of surgery until discharge. Visual Analogue Scale (VAS) pain scores will be collected.

Post-Op Visit:

Patients will follow-up at Neurosurgery clinic at 10-14 days postoperatively. At this time daily opioid usage will be assessed and converted to morphine equivalents/24 hr. At this visit: pain medication review form, and the Pain Catastrophizing Scale (PCS) (Sullivan, 1995). PROMIS Emotional Distress-Anxiety Short Form and PROMIS Emotional Distress-Depression Short Form, Brief Psychiatric Rating Scale and Neuro-QoL Short Form v1.1 - Satisfaction with Social Roles and Activities will also be completed by the participant.

6-Week Follow-Up Visit:

The participant will be asked to come to the Aiken Medical Building, Suite 407 approximately 6 weeks after their surgery. Investigators will work with the participant to determine their post-operative opioid dose regimen. Prior to taking their pain medication, the participant will then be administered a cold-pressor pain sensitivity test, in a manner identical to that use during the pre-operative assessment.In addition to the McGill Pain Questionnaire-Short form, a pain medication review form, the Pain Catastrophizing Scale (PCS) (Sullivan, 1995), the PROMIS Emotional Distress-Anxiety Short Form, the PROMIS Emotional Distress-Depression Short Form, Brief Psychiatric Rating Scale and Neuro-QoL Short Form v1.1 - Satisfaction with Social Roles and Activities will also be completed.

Eligibility criteria: Inclusion Criteria

* 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

Exclusion Criteria

* 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)

Primary outcomes:
measure: Post-surgical Hydromorphone Patient Care Assistance (PCA) Opioid Utilization
timeFrame: 72 hours postoperatively
measure: Post-surgical Pain Rating Using the Visual Analog Scale (VAS)
timeFrame: 72 hours post-operatively
measure: Post-surgical Opioid Utilization Using Electronic Medication Review
timeFrame: 72 hours post-operatively
measure: Post-surgical Opioid Utilization Using Electronic Medication Review
timeFrame: 6-week follow-up visit
measure: Pre-surgical Opioid Utilization Using the Pain Medication Review Form
timeFrame: Screening visit
measure: Pre-surgical Pain Rating Using the Visual Analog Scale (VAS)
timeFrame: Screening visit
Secondary outcomes:
measure: Pre-surgical Emotional Distress Related to Depression
timeFrame: Screening visit
measure: Post-surgical Emotional Distress Related to Depression
timeFrame: Day 10-14 Post-Operative Visit
measure: Post-surgical Emotional Distress Related to Depression
timeFrame: 6-week follow-up visit
measure: Pre-surgical Emotional Distress Related to Anxiety
timeFrame: Screening visit
measure: Post-surgical Emotional Distress Related to Anxiety
timeFrame: Day 10-14 Post-Operative Visit
measure: Post-surgical Emotional Distress Related to Anxiety
timeFrame: 6-week follow-up visit
measure: Pre-surgical Satisfaction With Social Roles and Activities
timeFrame: Screening visit
measure: Post-surgical Satisfaction With Social Roles and Activities
timeFrame: Day 10-14 Post-Operative Visit
measure: Post-surgical Satisfaction With Social Roles and Activities
timeFrame: 6-week follow-up visit
measure: Pre-surgical Pain Rating Using the Pain Catastrophizing Scale
timeFrame: Screening visit
measure: Post-surgical Pain Rating Using the Pain Catastrophizing Scale
timeFrame: Day 10-14 Post-Operative Visit
measure: Post-surgical Pain Rating Using the Pain Catastrophizing Scale
timeFrame: 6-week follow-up visit
measure: Pre-surgical Opioid Analgesic Efficacy Using the Cold-Pressor Pain Sensitivity Test
timeFrame: Screening visit
measure: Post-surgical Opioid Analgesic Efficacy Using the Cold-Pressor Pain Sensitivity Test
timeFrame: 6-week follow-up visit
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: Jacques E Chelly, MD
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Jacques E Chelly, MD
role: PRINCIPAL_INVESTIGATOR
References: