Subdissociative Dose Ketamine for Treatment of Acute Pain in Subjects With Chronic Pain

Subdissociative Dose Ketamine for Treatment of Acute Pain in Subjects With Chronic Pain: A Randomized Controlled Trial

This is a prospective, randomized controlled trial which will be conducted to determine whether sub-dissociative dose ketamine (SDDK) can improve pain control in subjects with chronic pain syndrome presenting to the emergency department with exacerbation of their chronic pain. The investigators also aim to determine whether use of SDDK can reduce the amount of subsequent opioid pain medications required for adequate pain relief in this population.

Study Overview

• Status: Completed
• Conditions: Chronic Pain
• Intervention / Treatment: Drug: Placebo; Drug: Ketamine

Detailed Description

1. The informed consent process will be initiated by investigators in the emergency department.
2. All potential subjects will be informed that participation in the study could lead to a positive urine drug test that could remain positive for up to a month after the conclusion of the study.
3. Female subjects of child bearing age, will have a pregnancy test performed prior to enrollment; any subjects who are pregnant will be excluded from this project.
4. Each subject will be asked to grade his/her pain severity on a 100mm non-hatched visual analog scale (VAS) ranging from 0 (no pain) to 100 (worst, maximum pain).
5. Each subject will be asked to fill out a baseline pain questionnaire
6. Each subject will be placed on monitors for continuous pulse oximetry, Heart Rate, Respiratory Rate, and blood pressure every 5 minutes for the duration of the study of one hour and longer for any patient who needs continued care. The patients temperature will be taken prior to the start of the protocol.
7. Each subject will have an intravenous catheter placed.
8. Each subject will be sequentially assigned to one of three treatment groups, based on a computer-generated randomization schedule, to receive an intravenous infusion of sub-dissociative Ketamine (0.25mg/kg), sub-dissociative dose Ketamine (0.5mg/kg), or an equal amount of normal saline.
9. All medications will be prepared by an emergency department pharmacist and all study medication intravenous bags will be identical in appearance and will be administered by the emergency department nurse caring for the patient who will be blinded to the study drug.
10. Each subject will receive lightly tinted sunglasses to wear during the duration of the study to minimize bias as ketamine can evoke a tell-tale short- lived nystagmus
11. Each subject will receive the study medication over a 20 minute period via an automated pump. At this point, the subjects will be asked to rate their pain on a VAS and asked if they need additional pain medication that will consist of intravenous hydromorphone with the dose and frequency determined by the discretion of the treating physician and documented on the data collection sheet.

• Study Type: Interventional
• Enrollment (Actual): 106
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Torrance, California, United States, 90501
      • Emergency Department, Harbor-UCLA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All adult subjects over the age of 18 with chronic pain* presenting to the emergency department with exacerbation of their chronic pain as their primary complaint
• Subjects who are willing and able to provide informed consent. *Chronic pain defined as greater > 3 months of symptoms and an initial VAS pain score > 70

Exclusion Criteria:

• History of overt psychosis, severe hypertension as defined by Systolic Blood Pressure > 180 mm Hg or Diastolic Blood Pressure >110 mm Hg, unstable angina, Coronary Artery Disease, Congestive Heart Failure, porphyrias, thyroid disease, seizure disorder, inability to provide informed consent: dementia, non-English/Spanish speakers, subjects in custody, suicidal, or clinically intoxicated.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; placebo controlled arm	Drug: Placebo; Normal Saline; Other Names: Normal Saline
Experimental: very low dose ketamine; 0.25 mg/kg of sub-dissociative ketamine as an experimental arm	Drug: Ketamine; sub-dissociative ketamine; Other Names: ketalar
Experimental: low dose ketamine; 0.50 mg/kg of sub-dissociative ketamine as an experimental arm	Drug: Ketamine; sub-dissociative ketamine; Other Names: ketalar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Compare the Percentage of Subjects Who Achieved Significant Pain Relief Between the 3 Treatment Groups as Measured by a Visual Analog Pain Scale at 60 Minutes A Decrease of at Least 20 mm on the VAS Will be Considered "Significant" Pain Relief	The primary endpoint was clinically significant pain relief defined a priori as a decrease in the pain VAS of at least 20 mm from baseline, which was arbitrarily chosen as the minimal amount that may be important to this group of patients and was extrapolated from studies of acute pain management in the ED. Using an effect size of 20-mm change in VAS as the marker for a successful outcome and the proportion of successes by group as the analysis point, we performed a power analysis using three groups: 0.5 mg/kg ketamine, 0.25 mg/kg ketamine, and placebo and found that a sample size of 96 subjects would be required to detect a statistically significant difference among groups with a power of 90% (a = 0.05). Expecting a loss of 10% of subjects due to patient withdrawal or incomplete data, 106 subjects were recruited. Only subjects who completed the 60-minute study and had data recorded for each of the time points were included in the analysis.	60 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess the Risk for Adverse Events Associated With Sub-dissociative Dose Ketamine	Subjects will be continuously assessed for complications secondary to the sub-dissociative ketamine	1 hour

Collaborators and Investigators

• Sponsor: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
• Collaborators: Air Force Research Laboratory
• Investigators: Principal Investigator: David Tanen, MD, Los Angeles Biomedical Institute

Publications and helpful links

General Publications

• Lumanauw DD, Youn S, Horeczko T, Yadav K, Tanen DA. Subdissociative-dose Ketamine Is Effective for Treating Acute Exacerbations of Chronic Pain. Acad Emerg Med. 2019 Sep;26(9):1044-1051. doi: 10.1111/acem.13755. Epub 2019 Apr 29.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2017
• Primary Completion (Actual): June 22, 2018
• Study Completion (Actual): September 1, 2019

Study Registration Dates

• First Submitted: September 28, 2016
• First Submitted That Met QC Criteria: September 29, 2016
• First Posted (Estimate): September 30, 2016

Study Record Updates

• Last Update Posted (Actual): April 15, 2021
• Last Update Submitted That Met QC Criteria: March 18, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Chronic Pain; Acute Pain; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Ketamine
• Other Study ID Numbers: 30612-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No