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

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ClinicalTrials.gov Identifier: NCT03959852
Recruitment Status : Recruiting
First Posted : May 22, 2019
Last Update Posted : September 6, 2019
Sponsor:
Information provided by (Responsible Party):
Mercy Health Ohio

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Pain, Acute Drug: Fentanyl Combination Product: Fentanyl and Ketamine Drug: Ketamine Phase 4

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 334 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: A Combination Study With Sub-Dissociative Ketamine and Fentanyl to Treat Moderate to Severe Pain in the Emergency Department
Estimated Study Start Date : September 2019
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine


Arms and Interventions
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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 Name: 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 Name: 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.


Outcome Measures
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Primary Outcome Measures :
  1. 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

  2. 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

  3. 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


Secondary Outcome Measures :
  1. OARRS report [ Time Frame: ED encounter (less than 24 hours) ]
    A retrospective review of OARRS report will be performed with each patient.

  2. 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


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03959852


Contacts
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Contact: Amanda Mason, DO 3307747142 afmason@mercy.com
Contact: Kenneth Shum, DO 4024304243 Kshum2@mercy.com

Locations
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United States, Ohio
St. Elizabeth Boardman Hospital Recruiting
Boardman, Ohio, United States, 44512
Contact: Amanda Mason, DO    330-774-7142      
Sponsors and Collaborators
Mercy Health Ohio
Investigators
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Study Director: David Gemmel Director of Research
More Information
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Additional Information:
(WONDER), W.-r. o. (2017, August 30). Centers for Disease Control and Prevention. Retrieved August 18, 2018, from CDC.gov: https://www.cdc.gov/drugoverdose/epidemic/index.html  This link exits the ClinicalTrials.gov site U.S. Department of Health and Human Services. (2018, October 15). U.S. Food and Drug Administration. Retrieved October 15, 2018, from https://www.accessdata.fda.gov/scripts/drugshortages/  This link exits the ClinicalTrials.gov site

Publications:

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Responsible Party: Mercy Health Ohio
ClinicalTrials.gov Identifier: NCT03959852     History of Changes
Other Study ID Numbers: 18-040
First Posted: May 22, 2019    Key Record Dates
Last Update Posted: September 6, 2019
Last Verified: September 2019

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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
Keywords provided by Mercy Health Ohio:
Moderate
Severe
Pain
Additional relevant MeSH terms:
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Acute Pain
Pain
Neurologic Manifestations
Signs and Symptoms
Fentanyl
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
Analgesics, Opioid
Narcotics
Adjuvants, Anesthesia