IN Sub-Dissociative Ketamine vs IN Fentanyl

Randomized Controlled Trial of Intranasal Ketamine Compared to Intranasal Fentanyl for Analgesia in Children With Suspected, Isolated Extremity Fractures in the Pediatric Emergency Department

This single center, randomized control, double blind trial will prospectively examine the feasibility of intranasal, sub-dissociative (IN) ketamine versus intranasal fentanyl for pain control in the pediatric emergency department setting. The investigators hypothesize that IN ketamine may provide a safe and effective alternative to IN fentanyl for children with suspected, isolated extremity fractures.

Eighty children ages 3-17 years with a suspected, isolated extremity fracture that requires analgesia will be randomized to receive IN ketamine or IN fentanyl upon presentation to the emergency department and will be followed for 2 hours for efficacy and 6 hours for safety.

Study Overview

• Status: Completed
• Conditions: Bone Fracture
• Intervention / Treatment: Drug: ketamine; Drug: ibuprofen or acetaminophen; Drug: fentanyl

Detailed Description

Intranasal medications are commonly used in place of parenteral opioids in children. IN fentanyl is the most commonly used intranasal analgesic medication in the pediatric population with demonstrated safety and efficacy comparable to IV fentanyl and IV morphine. IN ketamine, at sub-dissociative doses, offers similar safety and efficacy to IN fentanyl and the additional advantage of potentially reducing the total use of opioid agents during the emergency department visit. Ketamine is easily stored and has a wide therapeutic window with an extremely low risk of cardiorespiratory complications. This study will compare the safety and efficacy of IN ketamine to IN fentanyl in children with suspected, isolated extremity fractures in the pediatric emergency department.

The primary aim of the study is to examine the feasibility of future protocol expansion. The investigators will conclude that additional studies are NOT feasible if the observed rate of side effects for ketamine that exceeds fentanyl by three-fold or event rate of 5% or more for ketamine-related SAEs. The primary aim of the study will compare the frequency of adverse events over 6-hours among children randomized to receive either intranasal sub-dissociative ketamine (IN ketamine) or intranasal fentanyl (IN fentanyl) for pain control in the emergency department. The exploratory aim of the study will compare the efficacy of intranasal ketamine to intranasal fentanyl as measured by a reduction in age appropriate pain scale scores over 2-hours. The secondary aim of the study will compare the total dose of opioid pain medication in morphine equivalents/kg/hour required during the ED evaluation of children with suspected, isolated extremity fractures after randomization and treatment with IN ketamine or IN fentanyl.

Eighty children ages 3-17 years with a suspected, isolated extremity fracture that requires analgesia will be randomized to receive IN ketamine or IN fentanyl upon presentation to the emergency department and will be followed for 2 hours for efficacy and 6 hours for safety.

All participants will be premedicated with acetaminophen or ibuprofen and baseline data, including pain level, will be collected. The trial consists of two treatment arms. (IN ketamine 1 mg/kg or IN fentanyl 1.5 mcg/kg). Randomization will follow a 1:1 ratio, with approximately 40 per group. Randomization will be stratified by ages 3-10 and 11-17. The participants will be assessed by a research coordinator for adverse events every 5 minutes using an adverse events checklist for the first fifteen minutes post study medication administration and every 30 minutes for the first two hours after drug administration. The vital signs and pain scale assessment will be repeated every 10 minutes for the first 30 minutes and then every 30 minutes for the first two hours after drug administration. A final assessment will be made 6 hours after the last dose of study drug or at discharge from the ED to assess for late side effects or adverse events. Study medication may be repeated times one at a reduced dose after 20 minutes when the full effects of the first dose are known. The decision to administer additional study medication (0.5 mg/kg ketamine or 0.75 mcg/kg fentanyl ) will at be at the discretion of the treating physician. Should a second dose of study medication be required, a new schedule of patient assessments will commence following the same schedule as for the first dose. Participant assessments will continue until the 2 hour endpoint is reached from the time of the last drug administration, with a final assessment at 6 hours after the last dose of study drug or at discharge from the ED to assess for late side effects or adverse events.

• Study Type: Interventional
• Enrollment (Actual): 87
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Medical Center Main - Levine Children's Hospital Emergency Department

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• single suspected, isolated extremity fracture that requires analgesia

Exclusion Criteria:

• GCS < 15 at ED presentation,
• reported allergy or adverse reaction to ketamine or fentanyl,
• pregnancy,
• intoxication,
• hypotension (less than 70 mmHg +2x age or less than 90 mm Hg for patients greater than 11 years of age)
• weight > 70 kg
• patients receiving opioid analgesia administered prior to arrival
• multiply injured patients (injuries to multiple extremities)
• aberrant nasal anatomy that precludes IN medications

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ketamine; ketamine (1mg/kg)	Drug: ketamine; intranasal (IN) sub-dissociative ketamine (1mg/kg); Other Names: intranasal pain medication; Drug: ibuprofen or acetaminophen; 10 mg/kg of ibuprofen or 15 mg/kg of acetaminophen will be given to participants prior to the randomized intervention
Active Comparator: fentanyl; fentanyl (1.5 micrograms/kg)	Drug: ibuprofen or acetaminophen; 10 mg/kg of ibuprofen or 15 mg/kg of acetaminophen will be given to participants prior to the randomized intervention; Drug: fentanyl; Intranasal (IN) fentanyl (1.5 micrograms/kg); Other Names: intranasal pain medication

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Outcome: Number of Participants With Minor Side Effects and Significant Adverse Events	We will conclude that such a study is NOT feasible if we observe a rate of side effects for ketamine that exceeds fentanyl by three-fold or event rate of 5% or more for ketamine-related significant adverse events. Side effects are common events experienced by patients receiving ketamine or fentanyl that do not change outcomes for the patient but may affect the patient experience. A significant adverse event (SAE) includes any adverse event that begins after the short form consent has been completed that causes a threat to life, limb or an organ system, causes prolongation of hospitalization, or requires new medical or surgical treatment to correct.	60 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Outcome: Total Dose of Opioid Pain Medication in Morphine Equivalents/kg/Hour	Compare the total dose of opioid pain medication in morphine equivalents/kg/hour required during the ED evaluation of children with suspected forearm fractures after randomization and treatment with IN ketamine or IN fentanyl.	participants will be followed during the emergency department length of stay, estimated to average 6 hours

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory Outcome: Reduction in Age Appropriate Pain Scale Scores	Mean difference in the reduction of the pain scale scores at 20 minutes. Two commonly used, age appropriate and previously validated, pediatric pain assessment tools were used: FACES Pain Scale - Revised for children ages 4-10 and the Visual Analog Scale for children ages 11-17. The FACES Pain Scale - Revised is a self-reported measure of pain intensity developed for children with pain intensity represented by images of grimacing faces on a scale of 0 (no pain) to 10 (maximum pain). The Visual Analog Scale is a self-reported measure of pain intensity where patients mark their pain level on a 10 cm line that represents a continuum of no pain at 0 cm and worst pain at 10 cm. For analysis, pain scale data were merged and reported as values form 0 to 100. The minimum clinically significant reduction in pain was defined as a decrease of 20.	20 minutes
Secondary Safety Outcome: Adverse Events Over 6 Hours	Compare the frequency of types of adverse events over 6-hours among children randomized to receive either intranasal sub-dissociative ketamine (IN ketamine) or intranasal fentanyl (IN fentanyl) for pain control in the emergency department.	6 hours

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: Carolinas Trauma Network Research Group; Charlotte, Houston, Milwaukee Prehospital Emergency Research Nodal Center-CHaMP-ERNC
• Investigators: Principal Investigator: Stacy Reynolds, MD, Carolinas Medical Center

Publications and helpful links

General Publications

• Reynolds SL, Studnek JR, Bryant K, VanderHave K, Grossman E, Moore CG, Young J, Hogg M, Runyon MS. Study protocol of a randomised controlled trial of intranasal ketamine compared with intranasal fentanyl for analgesia in children with suspected, isolated extremity fractures in the paediatric emergency department. BMJ Open. 2016 Sep 8;6(9):e012190. doi: 10.1136/bmjopen-2016-012190.

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Actual): November 1, 2016
• Study Completion (Actual): November 1, 2016

Study Registration Dates

• First Submitted: August 5, 2015
• First Submitted That Met QC Criteria: August 11, 2015
• First Posted (Estimate): August 13, 2015

Study Record Updates

• Last Update Posted (Actual): July 26, 2022
• Last Update Submitted That Met QC Criteria: June 30, 2022
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Fractures, Bone; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Enzyme Inhibitors; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antipyretics; Analgesics, Opioid; Narcotics; Adjuvants, Anesthesia; Ketamine; Fentanyl; Acetaminophen; Ibuprofen; Analgesics
• Other Study ID Numbers: INK-2015