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

• ClinicalTrials.gov Identifier: NCT02920528
• Recruitment Status: Completed
• First Posted: September 30, 2016
• Last Update Posted: July 31, 2020
• Sponsor: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
• Collaborator: Air Force Research Laboratory
• Information provided by (Responsible Party): David Tanen, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Chronic Pain	Drug: Ketamine; Drug: Placebo	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 106 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Subdissociative Dose Ketamine for Treatment of Acute Pain in Subjects With Chronic Pain: A Randomized Controlled Trial
• Actual Study Start Date: May 1, 2017
• Actual Primary Completion Date: June 22, 2018
• Actual Study Completion Date: September 1, 2019

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; placebo controlled arm	Drug: Placebo; Normal Saline; Other Name: 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 Name: ketalar
Experimental: low dose ketamine; 0.50 mg/kg of sub-dissociative ketamine as an experimental arm	Drug: Ketamine; sub-dissociative ketamine; Other Name: ketalar

Outcome Measures

Primary Outcome Measures :

1. Compare pain relief between the 3 treatment groups as measured by the VAS. A decrease of at least 20mm on the VAS will be considered "significant" pain relief [ Time Frame: 1 hour ]
   Subjects pain will be assessed by VAS at 20, 40 and 60 minutes. Differences at 60 minutes will be compared for the primary outcome

Secondary Outcome Measures :

1. Compare total dosage of IV hydromorphone needed as rescue therapy to achieved adequate pain relief [ Time Frame: 1 hour ]
   Compare need for rescue therapy at the completion of the 1 hour study
2. Assess the risk for complications of sub-dissociative dose ketamine [ Time Frame: 1 hour ]
   Subjects will be continuously assessed for complications secondary to the sub-dissociative ketamine

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, California

Emergency Department, Harbor-UCLA Medical Center

Torrance, California, United States, 90501

Sponsors and Collaborators

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Air Force Research Laboratory

Investigators

• Principal Investigator: David Tanen, MD; Los Angeles Biomedical Institute

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: David Tanen, Professor of Emergency Medicine, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
• ClinicalTrials.gov Identifier: NCT02920528
• Other Study ID Numbers: 30612-01
• First Posted: September 30, 2016
• Last Update Posted: July 31, 2020
• Last Verified: July 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Additional relevant MeSH terms:

Chronic Pain; Acute Pain; Pain; Neurologic Manifestations; Ketamine; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Central Nervous System Depressants; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action