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Pain Reduction With Intranasal Medications for Extremity Injuries (PRIME)

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ClinicalTrials.gov Identifier: NCT02778880
Recruitment Status : Completed
First Posted : May 20, 2016
Results First Posted : September 1, 2020
Last Update Posted : September 1, 2020
Sponsor:
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati

Tracking Information
First Submitted Date  ICMJE April 19, 2016
First Posted Date  ICMJE May 20, 2016
Results First Submitted Date  ICMJE July 28, 2020
Results First Posted Date  ICMJE September 1, 2020
Last Update Posted Date September 1, 2020
Actual Study Start Date  ICMJE March 31, 2016
Actual Primary Completion Date February 22, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 18, 2020)
Difference From Baseline in Visual Analog Scale Pain Score [ Time Frame: 30 minutes after study medication ]
A VAS score is a self reported pain score of 0-100 millimeters (0 = no pain; 100 = worst possible pain). A decrease in a VAS score indicates a decrease in pain severity.
Original Primary Outcome Measures  ICMJE
 (submitted: May 19, 2016)
Visual Analog Scale Pain Score [ Time Frame: 30 minutes ]
Self reported pain score 30 minutes after study medication administration. Score is 0-100 mm (0 = no pain; 100 = worst pain imaginable)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 18, 2020)
  • Difference From Baseline in Visual Analog Scale Pain Score [ Time Frame: 15 minutes after study medication ]
    A VAS score is a self reported pain score of 0-100 millimeters (0 = no pain; 100 = worst possible pain). A decrease in a VAS score indicates a decrease in pain severity.
  • Difference From Baseline in Visual Analog Scale Pain Score [ Time Frame: 60 minutes after study medication ]
    A VAS score is a self reported pain score of 0-100 millimeters (0 = no pain; 100 = worst possible pain). A decrease in a VAS score indicates a decrease in pain severity.
  • Highest Achieved University of Michigan Sedation Scale (UMSS) Score [ Time Frame: 15, 30, and 60 minutes after study medication administration ]
    The University of Michigan Sedation Scale is a valid and reliable tool that allows for rapid assessment of the depth of sedation in children. It is a simple observational tool that assesses the level of alertness on a five-point scale. It has been validated in children and has shown to have significant inter-rater reliability. Score is 0-4 (0 = awake and alert; 1= minimally sedated; 2 = moderately sedated; 3 = deeply sedated; 4 = unarousable)
  • Rescue Analgesia [ Time Frame: Within the first 60 minutes after study medication ]
    Documentation of additional pain medication after study medication administration
  • Heart Rate [ Time Frame: 15 minutes after study medication ]
  • Heart Rate [ Time Frame: 30 minutes after study medication ]
  • Heart Rate [ Time Frame: 60 minutes after study medication ]
  • Respiratory Rate [ Time Frame: 15 minutes after study medication ]
  • Respiratory Rate [ Time Frame: 30 minutes after study medication ]
  • Respiratory Rate [ Time Frame: 60 minutes after study medication ]
  • Systolic Blood Pressure [ Time Frame: 15 minutes after study medication ]
  • Systolic Blood Pressure [ Time Frame: 30 minutes after study medication ]
  • Systolic Blood Pressure [ Time Frame: 60 minutes after study medication ]
  • Diastolic Blood Pressure [ Time Frame: 15 minutes after study medication ]
  • Diastolic Blood Pressure [ Time Frame: 30 minutes after study medication ]
  • Diastolic Blood Pressure [ Time Frame: 60 minutes after study medication ]
  • Oxygen Saturation [ Time Frame: 15 minutes after study medication ]
  • Oxygen Saturation [ Time Frame: 30 minutes after study medication ]
  • Oxygen Saturation [ Time Frame: 60 minutes after study medication ]
  • Capnometry Value [ Time Frame: 15 minutes after study medication ]
  • Capnometry Value [ Time Frame: 30 minutes after study medication ]
  • Capnometry Value [ Time Frame: 60 minutes after study medication ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 19, 2016)
  • University of Michigan Sedation Scale Score [ Time Frame: 15, 30 and 60 minutes ]
    Clinician reported sedation score 15, 30 and 60 minutes after study medication administration. Score is 0-4 (0 = awake and alert; 4 = unarousable)
  • Adverse Events [ Time Frame: 15, 30 and 60 minutes ]
    Self and clinician reported adverse events 15, 30 and 60 minutes after study medication administration
  • Additional opioid pain medication administration after study medication [ Time Frame: 15, 30 and 60 minutes ]
    Documentation of additional pain medication at 15, 30 and 60 minutes after study medication administration
  • Visual Analog Scale Pain Score [ Time Frame: 15 and 60 minutes ]
    Self reported pain score 15 and 60 minutes after study medication administration. Score is 0-100 mm (0 = no pain; 100 = worst pain imaginable)
  • Heart Rate [ Time Frame: 15, 30 and 60 minutes ]
    Clinician obtained heart rate 15, 30 and 60 minutes after study medication administration.
  • Respiratory Rate [ Time Frame: 15, 30 and 60 minutes ]
    Clinician obtained respiratory rate 15, 30 and 60 minutes after study medication administration.
  • Blood pressure [ Time Frame: 15, 30 and 60 minutes ]
    Clinician obtained blood pressure 15, 30 and 60 minutes after study medication administration.
  • Oxygen saturation [ Time Frame: 15, 30 and 60 minutes ]
    Clinician obtained oxygen saturation 15, 30 and 60 minutes after study medication administration.
  • Capnometry value [ Time Frame: 15, 30 and 60 minutes ]
    Clinician obtained capnometry value 15, 30 and 60 minutes after study medication administration.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pain Reduction With Intranasal Medications for Extremity Injuries
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Pain
  • Traumatic Limb Injury
Intervention  ICMJE
  • Drug: Ketamine
    Other Name: Ketalar
  • Drug: Fentanyl
Study Arms  ICMJE
  • Experimental: Ketamine
    Ketamine 1.5 mg/kg intranasally for one dose
    Intervention: Drug: Ketamine
  • Active Comparator: Fentanyl
    Fentanyl 2 mcg/kg intranasally for one dose
    Intervention: Drug: Fentanyl
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 19, 2016)
90
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE March 21, 2017
Actual Primary Completion Date February 22, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 8 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02778880
Other Study ID Numbers  ICMJE CIN_PRIME_001
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Children's Hospital Medical Center, Cincinnati
Study Sponsor  ICMJE Children's Hospital Medical Center, Cincinnati
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Theresa M Frey, MD Children's Hospital Medical Center, Cincinnati
Principal Investigator: Matthew R Mittiga, MD Children's Hospital Medical Center, Cincinnati
PRS Account Children's Hospital Medical Center, Cincinnati
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP