Clinical trial NCT02778880: Pain Reduction With Intranasal Medications for Extremity Injuries
Official title: A Randomized Controlled Trial of Intranasal Sub-dissociative Dosing of Ketamine Compared to Intranasal Fentanyl for Treatment of Pain Associated With Acute Extremity Injuries in Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pain
Traumatic Limb Injury
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
First posted: 2016-05-20
Enrollment: 90
Sex: ALL
Minimum age (years): 8
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study compares the analgesic effect of intranasal sub-dissociative dosing of ketamine and intranasal fentanyl in children presenting to the Emergency Department with acute extremity injuries.

Detailed description: Inadequate pain control, especially in the emergency department (ED), is a major public health concern. Despite increased awareness, pain continues to be underdiagnosed and undertreated, particularly in the pediatric population. Children often encounter long delays in medication administration, possibly due to the time required to obtain intravenous access. The intranasal administration route offers a more efficient alternative for faster and noninvasive delivery of pain medication. This route is gaining popularity secondary to its rapid onset of active, minimal discomfort and relative simplicity.

Opioids are the most commonly used class of analgesic pain medication for children presenting in severe pain due to traumatic injuries. Despite their potential effectiveness, opioids have several concerning adverse effects, particularly when administered prior to procedural sedation in children. Administration of pre-procedural sedation opioids is associated with an increased risk of serious adverse events (oxygen desaturation, apnea, and hypotension) as well as the need for significant interventions, such as bag-mask ventilation, intubation, and pharmacologic blood pressure support. In addition, due to genetic variations that may lead to increased or diminished opioid sensitivity, ideal dosing to adequately control severe pain yet avoid adverse medication-related side effects is difficult to ascertain. Many children in severe pain do not receive opioids, receive doses that are below those recommended or experience long delays in receiving opioids. The reasons for this are unclear, but the investigators speculate that this may be due in part to fear of adverse effects of opioids, provider inexperience with opioid use in children or fear of contributing to opioid tolerance or abuse. For all of these reasons, providers often seek non-opioid alternatives for pediatric patients with acute, severe pain.

Ketamine, in sub-dissociative doses administered by the intravenous or intranasal route, is emerging as an alternative medication for the treatment of moderate to severe pain in multiple settings. In adults, low dose ketamine is well tolerated and has been used successfully as an adjuvant and an alternative to opioids to provide rapid pain relief in the ED. As a dissociative anesthetic, ketamine is the most commonly used agent to facilitate painful procedures in the pediatric emergency department. At lower doses, it has been used in children to provide analgesia in a variety of acute and chronic pain settings, including terminal diagnoses, sickle cell disease, perioperative pain, traumatic injuries, extensive burns and conditions where opioids are contraindicated. Similar to adults, ketamine has been used via the intranasal route to provide adequate analgesia and sedation in children in the pre-hospital setting and in those undergoing procedures.

The objective of this study is to compare intranasal sub-dissociative ketamine with intranasal fentanyl for treatment of acute pain associated with traumatic limb injuries in children presenting to the ED and to document an objective respiratory side effect profile utilizing noninvasive capnometry. If found to be an effective analgesic, intranasal ketamine would be particularly useful in children who experience adverse effects with opioids, have developed opioid tolerance as a result of chronic painful conditions, have poor opioid sensitivity due to their genetic predisposition or in pediatric trauma patients with the potential for hypotension. Additionally, for patients that require procedural sedation for fracture reduction, avoiding opioids early in the emergency department visit may decrease sedation recovery time and the risk of serious adverse events during sedation.

Eligibility criteria: Inclusion Criteria:

* 8 years to 17 years (up to the 18th birthday)
* Presenting to emergency department with one or more extremity injuries
* Visual analog scale score 35 mm or greater
* Parent or legal guardian present and willing to provide written consent

Exclusion Criteria:

* Received narcotic pain medication prior to arrival
* Evidence of significant head, chest, abdomen, or spine injury
* Glasgow coma score less than 15 or unable to self report pain score
* Nasal trauma or aberrant nasal/airway anatomy
* Active epistaxis
* Allergy to ketamine, fentanyl or meperidine
* Non-English speaking parent and/or child
* History of psychosis
* Postmenarchal female without a urine or serum assay documenting the absence of pregnancy
* Brought in my juvenile detention center or in police custody
* Pregnancy

Primary outcomes:
measure: Difference From Baseline in Visual Analog Scale Pain Score
timeFrame: 30 minutes after study medication
Secondary outcomes:
measure: Difference From Baseline in Visual Analog Scale Pain Score
timeFrame: 15 minutes after study medication
measure: Difference From Baseline in Visual Analog Scale Pain Score
timeFrame: 60 minutes after study medication
measure: Highest Achieved University of Michigan Sedation Scale (UMSS) Score
timeFrame: 15, 30, and 60 minutes after study medication administration
measure: Rescue Analgesia
timeFrame: Within the first 60 minutes after study medication
measure: Heart Rate
timeFrame: 15 minutes after study medication
measure: Heart Rate
timeFrame: 30 minutes after study medication
measure: Heart Rate
timeFrame: 60 minutes after study medication
measure: Respiratory Rate
timeFrame: 15 minutes after study medication
measure: Respiratory Rate
timeFrame: 30 minutes after study medication
measure: Respiratory Rate
timeFrame: 60 minutes after study medication
measure: Systolic Blood Pressure
timeFrame: 15 minutes after study medication
measure: Systolic Blood Pressure
timeFrame: 30 minutes after study medication
measure: Systolic Blood Pressure
timeFrame: 60 minutes after study medication
measure: Diastolic Blood Pressure
timeFrame: 15 minutes after study medication
measure: Diastolic Blood Pressure
timeFrame: 30 minutes after study medication
measure: Diastolic Blood Pressure
timeFrame: 60 minutes after study medication
measure: Oxygen Saturation
timeFrame: 15 minutes after study medication
measure: Oxygen Saturation
timeFrame: 30 minutes after study medication
measure: Oxygen Saturation
timeFrame: 60 minutes after study medication
measure: Capnometry Value
timeFrame: 15 minutes after study medication
measure: Capnometry Value
timeFrame: 30 minutes after study medication
measure: Capnometry Value
timeFrame: 60 minutes after study medication
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Theresa M Frey, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital Medical Center, Cincinnati
name: Matthew R Mittiga, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Frey TM, Florin TA, Caruso M, Zhang N, Zhang Y, Mittiga MR. Effect of Intranasal Ketamine vs Fentanyl on Pain Reduction for Extremity Injuries in Children: The PRIME Randomized Clinical Trial. JAMA Pediatr. 2019 Feb 1;173(2):140-146. doi: 10.1001/jamapediatrics.2018.4582.