Sub-Dissociative Ketamine and Fentanyl to Treat Moderate to Severe Pain

September 9, 2020 updated by: Mercy Health Ohio

A Combination Study With Sub-Dissociative Ketamine and Fentanyl to Treat Moderate to Severe Pain in the Emergency Department

The objective of this study is to evaluate the potential opioid-sparing effect associated with the novel combination of fentanyl and sub-dissociative ketamine in adult patients with moderate to severe pain in the emergency department.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Pain is a very common complaint in the emergency department (ED). The use of opioids to treat moderate to severe pain has increased over the last decade as well as the number of opioid related deaths. In 1999 to 2016, more than 630,000 people died from a drug overdose. Treatment for acute pain has been assessed in the ED, with review of several different pain medications. Sub-dissociative ketamine (SDK) has become a valuable treatment option for acute pain and in recent years, has been of increased interest due to the growing concerns regarding opioid abuse and opioid shortage in the United States. Sub-dissociative ketamine, an NMDA receptor antagonist, has been studied in dose ranges of 1-4.5 mg/kg for dissociative sedation, as well as dose ranges of 0.1-0.3 mg/kg to treat pain. The onset of action for an IV dose of 2 mg/kg has been studied, with onset usually within 30 seconds after injection and anesthetic effect lasting 5-10 minutes. Common side effects include elevated blood pressure, diplopia or nystagmus, nausea and vomiting. More rare and more severe side effects in dissociative doses include respiratory depression, emergency phenomenon, tonic and clonic movements, and anaphylaxis. However, these were rarely, if ever seen, findings in sub-dissociative doses. Several studies indicate that SDK is a safe and effective alternative to opioids for patients with complaints of moderate to severe pain that provides adequate analgesic effect by itself. In particular, several studies have compared SDK versus morphine, particularly looking at pain in individuals with abdominal pain, flank pain, low back pain or musculoskeletal pain, and acute fractures. SDK has also shown to decrease opioid consumption and the need for rescue analgesia. The studies showed that that there was no difference in average pain scores, but the amount of morphine required was significantly decreased. SDK has proven to be a safe alternative, but the side effects, although short, make it less desirable to use. To the investigator's knowledge, there has never been a study focusing on the use of combination fentanyl and SDK. Fentanyl, an opioid agonist, has been studied in low dose forms of 2 mcg/kg for pain, moderate dose forms of 2-20 mcg/kg for major surgical procedures, and high dose forms of 20-50 mcg/kg for orthopedic and open heart surgeries. Onset of action is almost immediate when given IV, and maximal effect of the drug may take several minutes. The usual duration of action is 30-60 minutes. Common side effects include hypertension, hypotension, dizziness, blurred vision, nausea, vomiting and laryngospasm. Serious side effects included respiratory depression, apnea, rigidity, bradycardia, serotonin syndrome, adrenal insufficiency, and if left untreated could cause cardiac arrest and circulatory depression. There have been several combination studies with SDK, but none regarding fentanyl and ketamine. In one study, combination SDK and reduced dose hydromorphone produced rapid pain relief without significant side effects. Another study indicated that morphine and SDK both provided adequate pain relief alone, but combined morphine and SDK required less morphine administration, had faster onset of relief, and provided sustained reduction in pain intensity for up to 2 hours.

Study Type

Interventional

Enrollment (Actual)

6

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Boardman, Ohio, United States, 44512
        • St. Elizabeth Boardman Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • 18 - 65 years old
  • Moderate pain defined as 4-6 out of 10, severe pain defined as ≥ 7 out of 10 as defined by the numeric rating pain scale (NRS)
  • Proficient in reading and understanding English
  • Are deemed by the attending physician to require opioid therapy.

Exclusion Criteria:

  • Inability to give consent,
  • Inability to use the numeric rating scale (NRS) score
  • Long-term use of opioids, history of chronic pain
  • Known substance abuse known as excessive use of a drug such as (e.g. alcohol, narcotics or cocaine)
  • Known hypersensitivity to ketamine or fentanyl
  • Pregnancy
  • Alcohol intoxication
  • Depression
  • Anxiety
  • Chronic obstructive pulmonary disease
  • Asthma
  • Cirrhosis
  • On dialysis
  • Acute ischemic stroke
  • Heart rate (HR) less < 60 bpm or > 120 bpm
  • Systolic blood pressure (SBP) < 90 mmHg or > 180 mmHg
  • Ischemic heart disease
  • Ketamine prior to arrival
  • Trauma patients
  • Sepsis or septic shock
  • Weight > 100 kg.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Sub-Dissociative Ketamine alone
0.3 mg/kg of Sub-Dissociative Ketamine IV administered over at least 1 minute
Drug: Ketamine
0.3 mg/kg of Sub-Dissociative Ketamine IV administered over at least 1 minute
Other Names:
  • Ketamine Hydrochloride
Active Comparator: Fentanyl alone
1 mg/kg of Fentanyl IV administered over at least 1 minute
Drug: Fentanyl
1 mg/kg of Fentanyl IV administered over at least 1 minute
Other Names:
  • Fentanyl Citrate
Experimental: Sub-dissociative Ketamine and Fentanyl
Combined dose of 0.15 mg/kg of Sub-dissociative Ketamine and 0.5 mg/kg of Fentanyl IV administered over at least 1 minute
Combination product: Fentanyl and Ketamine
Combined dose of 0.15 mg/kg of Sub-dissociative Ketamine and 0.5 mg/kg of Fentanyl IV administered over at least 1 minute.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Analgesia of combination fentanyl and SDK as assessed using the pain scale 1-10
Time Frame: ED encounter (less than 24 hours)
Analgesia of combination fentanyl and SDK as assessed using the pain scale 1-10
ED encounter (less than 24 hours)
Analgesia of fentanyl as assessed using the pain scale 1-10
Time Frame: ED encounter (less than 24 hours)
Analgesia of fentanyl as assessed using the pain scale 1-10
ED encounter (less than 24 hours)
Analgesia of ketamine as assessed using the pain scale 1-10
Time Frame: ED encounter (less than 24 hours)
Analgesia of katamine as assessed using the pain scale 1-10
ED encounter (less than 24 hours)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
OARRS report
Time Frame: ED encounter (less than 24 hours)
A retrospective review of OARRS report will be performed with each patient.
ED encounter (less than 24 hours)
Opioid sparing response as assessed by number of times additional rescue doses of fentanyl were required
Time Frame: ED encounter (less than 24 hours)
Opioid sparing response as assessed by number of times additional rescue doses of fentanyl were required
ED encounter (less than 24 hours)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mercy Health Ohio

Investigators

  • Study Director: David Gemmel, Director of research

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 18, 2019

Primary Completion (Actual)

June 5, 2020

Study Completion (Actual)

June 5, 2020

Study Registration Dates

First Submitted

March 12, 2019

First Submitted That Met QC Criteria

May 21, 2019

First Posted (Actual)

May 22, 2019

Study Record Updates

Last Update Posted (Actual)

September 11, 2020

Last Update Submitted That Met QC Criteria

September 9, 2020

Last Verified

September 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 18-040

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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