Single-dose Ketamine for the Reduction of Pain and Depression in the Emergency Department

Single-dose Ketamine to Reduce Pain Severity, Depressive Symptoms and the Need for Opiates Both During and After Emergency Department Care

In this proposal, the investigators will determine if a single dose of intravenous (IV) ketamine (in combination with midazolam) reduces pain severity, depressive symptoms and need for opiate analgesics both in the ED and in the acute recovery period after ED discharge. The investigators will compare the ketamine arm to an active placebo-controlled arm (with midazolam).

Study Overview

• Status: Withdrawn
• Conditions: Depression; Acute Pain
• Intervention / Treatment: Drug: Ketamine; Drug: Midazolam; Drug: Placebo

Detailed Description

The investigators will enroll 120 medically stable adult patients who present to two Emergency Departments with a chief complaint of acute pain.

The investigators will randomly assign subjects using a blocked randomization schedule to either: 1) a single dose of IV ketamine (0.3 mg.kg) + midazolam, or 2) placebo + midazolam. ED providers and patients will be blind to treatment allocation.

All participants will complete measures of pain and mood scores every 30 minutes, and the investigators will record any analgesics administered in the ED until discharge. At 7-days and 14-days post- discharge, the investigators will measure summary reports of pain severity, mood, and analgesic medication used.

• Study Type: Interventional
• Phase: Phase 2; Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adults between the ages of 18-65
2. A chief complaint of painful condition (pain score ≥ 5 on the numeric rating scale [NRS] from 0-10 with anchors of 0 = "no pain" and 10 = "worst pain imaginable")
3. Expected to be in the ED for at least 2 hours

Exclusion Criteria:

1. Non-English speaking
2. Not medically suitable for ketamine per treating MD (e.g. medical condition where ketamine is contraindicated); ketamine or midazolam may be unsafe (e.g., known sensitivity, glaucoma, or other concerns)
3. Not alert and oriented
4. Active psychosis, self-injury, suicidal/homicidal intentions on initial evaluation by treating team
5. Seeking treatment due to a mental health or substance use disorder
6. History of chronic opioid use
7. Prescribed opioid use within the past 24 hours
8. Any use of recreational narcotics throughout lifetime
9. Sensitivity or allergy or intolerance to ketamine, opioids, and/or benzodiazepines
10. Weight > 170kg (375 lbs)
11. Current neurological disease (e.g., multiple sclerosis, stroke, brain tumor, seizure disorder, etc.)
12. Pregnancy
13. Prisoner

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Arm; Participants will be assigned to receive a single dose of IV ketamine (0.3 mg.kg) + midazolam	Drug: Ketamine; Ketamine is a medication approved by the US Food and Drug Administration (FDA) for anesthesia, sedation, and post-surgical pain treatment. It is not approved for emergency patients complaining of pain but is often used "off-label." Ketamine may be useful for acute pain management and in treatment of depressed mood. The purpose of this study is to determine whether a single low dose of ketamine can relieve pain and reduce negative mood for 2 weeks after emergency department (ED) treatment.; Drug: Midazolam; In this study, all patients will also receive midazolam. Midazolam is a sedative that typically makes people feel relaxed and is intended to increase comfort with ketamine and reduce anxiety.
Active Comparator: Active Placebo Arm; Participants will be assigned to receive a single dose of IV placebo + midazolam	Drug: Midazolam; In this study, all patients will also receive midazolam. Midazolam is a sedative that typically makes people feel relaxed and is intended to increase comfort with ketamine and reduce anxiety.; Drug: Placebo; In this study, patients in the active comparator group will receive midazolam first, then placebo. A placebo is an inactive solution that looks like the study drug, but contains no active ingredients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Intensity in the ED	Pain Numeric Rating Scale (PNRS)- this item is anchored to pain intensity "right now" on a scale from 0(no pain)-10 (worst pain imaginable)	Pain intensity rating in the ED at 1-hour post-study drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Intensity at Follow-Up	Pain Numeric Rating Scale (PNRS): this item is anchored to pain intensity within the past 7-days on a scale from 0 (no pain) to 10 (worst pain imaginable)	Pain Intensity at 1-week post-ED Discharge

Collaborators and Investigators

• Sponsor: Maria Pacella
• Collaborators: University of Pittsburgh Physicians
• Investigators: Principal Investigator: Maria L Pacella, PhD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2019
• Primary Completion (Actual): February 5, 2020
• Study Completion (Actual): February 5, 2020

Study Registration Dates

• First Submitted: January 31, 2018
• First Submitted That Met QC Criteria: February 9, 2018
• First Posted (Actual): February 19, 2018

Study Record Updates

• Last Update Posted (Actual): February 11, 2020
• Last Update Submitted That Met QC Criteria: February 7, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Pathologic Processes; Mood Disorders; Pain; Neurologic Manifestations; Disease Attributes; Depression; Depressive Disorder; Emergencies; 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; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Ketamine; Midazolam
• Other Study ID Numbers: PRO17090065

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: There is no plan in place yet because it is undecided whether the investigators will need to share the data with additional investigators/researchers not listed on the protocol.

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.: Yes