Intranasal Ketamine for Procedural Sedation (INK)
Primary Purpose
Bone Fractures, Dislocations
Status
Unknown status
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
IN ketamine
IV ketamine
IN saline 0.9%
IV saline 0.9%
Sponsored by
About this trial
This is an interventional treatment trial for Bone Fractures
Eligibility Criteria
Inclusion Criteria:
- Age 4 -17 years
- Up to 80 kg
- Presenting the paediatric emergency department
- Require a closed reduction by procedural sedation and analgesia
- Acute (=< 48 hours) distal radius and/or ulna fracture that is angulated with or without displacement
- No more than 0.5 cm shortening in either the radius or ulna (not both)
Exclusion Criteria:
- Previous hypersensitivity reaction to ketamine
- Globe rupture
- Traumatic brain injury with intracranial hemorrhage
- History of uncontrolled hypertension
- Nasal bone deformity
- Duration of reduction expected to be greater than 20 minutes
- Poor English or French fluency in the absence of a native language interpreter
- American Society of Anesthesiologists (ASA) class of 3 or greater
- Previous sedation with ketamine within 24 hours
- Previous diagnosis of schizophrenia or psychosis based on DSM-V criteria
- Pregnancy
- Neuro-cognitive impairment that precludes informed consent, assent, or ability to self-report pain and satisfaction
- Multi-limb trauma
- Hemodynamic compromise
- Glasgow coma score < 15
- Fracture is comminuted
- Fracture is associated with a dislocation
- Hematoma block at index visit
- Unilateral or bilateral nasal obstruction (due to infectious or allergic rhinitis, nasal polyps, septal hematoma, or septal deviation)
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
IN ketamine and IV saline
IV ketamine and IN saline
Arm Description
Ketamine, single dose, 10 mg/kg (0.1 mL/kg) of 100 mg/mL solution delivered intranasally using an atomizer and divided to both nares to a maximum of 800 mg (8 mL) AND 0.9% normal saline (NS) 0.02 to 0.03 mL/kg delivered intravenously to a maximum of 2.4 mL
Ketamine, single dose, 1 to 1.5 mg/kg (0.02 to 0.03 mL/kg) of 50 mg/mL solution delivered intravenously, to a maximum of 120 mg (2.4 mL) AND 0.9% normal saline (NS) 0.1 mL/kg delivered intranasally using an atomizer and divided to both nares, to a maximum of 8 mL
Outcomes
Primary Outcome Measures
Adequacy of sedation
Proportion with DOCS score -2 to +2 for duration of fracture reduction
Secondary Outcome Measures
Depth of sedation
Score using Pediatric Sedation State Scale
Onset of adequate sedation
Time interval from first IN sprays to first DOCS score between -2 and +2 in minutes
Duration of sedation
Duration of time between the first DOCS score -2 to +2 to last DOCS score between -2 and +2 post-fracture reduction
Proportion of time participant adequately sedated during fracture reduction
Proportion of time DOCS score is -2 to +2 during fracture reduction.
Adverse events
The proportion of participants with adverse effects between groups will be compared. The list of adverse effects was chosen based on known adverse effects associated with ketamine and consensus-based recommendations for reporting for procedural sedation and analgesia in children.
Length of stay due to PSA
Time interval from the first pair of IN sprays to discharge
Duration of procedure
Time of the first pair of IN sprays to the end of cast or splint application
Caregiver satisfaction
Obtained when patient is awake and drinking using a Visual Analog Scale; Parents not wishing to remain in proximity of child for sedation may opt out
Participant satisfaction
Obtained when patient is awake and drinking using a Visual Analog Scale; Satisfaction will only be assessed in children at least eight years of age as the VAS has not been validated in younger children.
Physician satisfaction
Obtained immediately prior to discharge using a Visual Analog Scale
Nurse satisfaction
Obtained immediately prior to discharge using a Visual Analog Scale
Requirement for additional sedative medication
Number of doses and type of adjunctive sedative medication required; Deemed inadequate if additional sedative medication given (for IN ketamine group only)
Analgesic medication
Number of doses and type of analgesic medication required
Pain
Pain scores will be recorded using the FPS-R on arrival and when the child is awake and drinking
Emergence delirium
The proportion of children experiencing emergence delirium will be compared using the Paediatric Anesthesia Emergence Delirium (PAED) scale scored from the video every 5 minutes by an outcome assessor starting when fracture reduction is complete to when awake and drinking
Nasal irritation
Measured using the Faces Pain Scale - Revised when awake and drinking
Successful sedation
Successful sedation - Based on the definition of Bhatt et al., this will be defined as no unpleasant patient recall of the procedure, no resistance or restraint required during the procedure, no permanent sedation-related complication or no sedation-related event requiring abandonment of the procedure.
Defined as: no unpleasant patient recall of the procedure, no resistance or restraint required during the procedure, no permanent sedation-related complication or no sedation-related event requiring abandonment of the procedure.
Defined as no unpleasant recall of procedure, no resistance or restraint, no permanent sedation related complication, no sedation-related event requiring abandonment of procedure
Adjunctive IV therapy
Other reasons for IV insertion (analgesia, anxiolysis, fluids, etc.)
Number of IN sprays received / Intended number of sprays
Number of IN sprays received / Intended number of sprays
Number of IV attempts
Number of IV attempts and time to IV insertion Number of IV attempts
Time to IV insertion
Time from first breakage of skin to establishment of successful flow with a flush
Full Information
NCT ID
NCT02828566
First Posted
June 30, 2016
Last Updated
August 25, 2017
Sponsor
Lawson Health Research Institute
1. Study Identification
Unique Protocol Identification Number
NCT02828566
Brief Title
Intranasal Ketamine for Procedural Sedation
Acronym
INK
Official Title
Intranasal Ketamine Versus Intravenous Ketamine for Procedural Sedation in Children: a Multi-centre Randomized Controlled Non-inferiority Trial
Study Type
Interventional
2. Study Status
Record Verification Date
March 2017
Overall Recruitment Status
Unknown status
Study Start Date
October 2017 (Anticipated)
Primary Completion Date
January 2019 (Anticipated)
Study Completion Date
February 2019 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Lawson Health Research Institute
4. Oversight
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.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study will examine the effectiveness of intranasal (IN) ketamine compared to standard intravenous (IV) ketamine administration for simple reductions of orthopaedic injuries in the paediatric population. The aim is to assess if IN administration is equivalent to the current standard of care, IV. The population to be studied is children 4-17 years of age who require a simple orthopaedic reduction. Following a double dummy approach to overcome the difficulty in masking interventions, each participant will receive both IV and IN interventions, only one of which will be the real drug. Procedural sedation and analgesia (PSA) will be assessed using the Dartmouth Operative Conditions Scale (DOCS).
Detailed Description
Randomization and concealment of allocation will be pharmacy-controlled using a computerized central randomization service. The treating physician, bedside nurse, research assistant, and participant will be blinded to the intervention. Eligible participants will be randomized in a 1:1 allocation ratio with a stratified block design of four or six to either (1) IN ketamine (each single dose, 10 mg/kg prepared in 0.9% NS in 3 mL syringe and atomizer, to a maximum of 8 mL) PLUS IV 0.9% NS 0.02 mL/kg or (2) IV ketamine (single dose, 1 mg/kg, to a maximum 80 mg) PLUS intranasal 0.9% NS 0.10 mL/kg divided to both nares. Due to the perceptible differences in interventional routes, each participant will receive both IV and IN interventions using this double-dummy approach. For IN dose volumes less than or equal to 0.5 mL, the entire dose will be delivered into 1 nostril and for doses greater than 0.5 mL, the dose will be divided equally between both nares. Adjunctive sedation will be given as needed in the form of IV ketamine, any dose, for participants who are adequately sedated 1 minute after IV administration at the discretion of the treating physician. Inadequate sedation in this context refers to one of the following: participant's vocalizations are consistent with pain OR participant withdraws or localizes due to pain. Eligible participants will be identified by the treating physician after viewing the radiographs and performing a clinical assessment. The physician will then inform a research assistant (RA) that the participant is eligible. The RA will then seek informed consent and explain the protocol to the family. Baseline demographic information will be obtained. Informed consent for PSA and a pre-anesthetic assessment will be performed by the treating physician in accordance with the usual standard of care. The RA will record a continuous video of the participant's entire body and monitor using an iPad starting immediately after the IV intervention until the participant is awake and able to tolerate oral fluids. DOCS scores will be obtained by two trained outcome assessors every 30 seconds for the entire duration of the video. The outcome assessors will also score the entire video for emergence delirium using the Paediatric Anesthesia Emergence Delirium (PAED) scale every 5 minutes beginning at the completion of fracture reduction until the participant is awake and drinking. Participants will receive standard monitoring of oxygen saturation, blood pressure, respiratory rate, apnea, heart rate, and rash by the attending nurse and physician every 5 minutes as per the usual standard of care. The usual standard of care also includes monitoring post-anesthetic for the presence of known idiosyncratic effects of ketamine that include vomiting, seizure, headache, emergence reaction, and hypersensitivity. The RA will obtain this information from the nursing record at discharge and based on consensus-based Canadian recommendations. Immediately prior to discharge, the RA will also record the duration of stay in the ED, parental, patient, and physician satisfaction with PSA using a 5-item Likert scale, and nasal irritation
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bone Fractures, Dislocations
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
470 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
IN ketamine and IV saline
Arm Type
Experimental
Arm Description
Ketamine, single dose, 10 mg/kg (0.1 mL/kg) of 100 mg/mL solution delivered intranasally using an atomizer and divided to both nares to a maximum of 800 mg (8 mL) AND 0.9% normal saline (NS) 0.02 to 0.03 mL/kg delivered intravenously to a maximum of 2.4 mL
Arm Title
IV ketamine and IN saline
Arm Type
Active Comparator
Arm Description
Ketamine, single dose, 1 to 1.5 mg/kg (0.02 to 0.03 mL/kg) of 50 mg/mL solution delivered intravenously, to a maximum of 120 mg (2.4 mL) AND 0.9% normal saline (NS) 0.1 mL/kg delivered intranasally using an atomizer and divided to both nares, to a maximum of 8 mL
Intervention Type
Drug
Intervention Name(s)
IN ketamine
Other Intervention Name(s)
ketamine hydrochloride
Intervention Description
Intranasal ketamine 100 mg/mL solution (10 mg/kg, maximum 800 mg)
Intervention Type
Drug
Intervention Name(s)
IV ketamine
Other Intervention Name(s)
ketamine hydrochloride
Intervention Description
Intravenous ketamine 50 mg/mL solution (1 to 1.5 mg/kg, maximum 120 mg)
Intervention Type
Drug
Intervention Name(s)
IN saline 0.9%
Intervention Description
Intranasal 0.9% normal saline
Intervention Type
Drug
Intervention Name(s)
IV saline 0.9%
Intervention Description
Intravenous 0.9% normal saline
Primary Outcome Measure Information:
Title
Adequacy of sedation
Description
Proportion with DOCS score -2 to +2 for duration of fracture reduction
Time Frame
Duration of fracture reduction
Secondary Outcome Measure Information:
Title
Depth of sedation
Description
Score using Pediatric Sedation State Scale
Time Frame
Duration of fracture reduction
Title
Onset of adequate sedation
Description
Time interval from first IN sprays to first DOCS score between -2 and +2 in minutes
Time Frame
Within 1 hour following intervention
Title
Duration of sedation
Description
Duration of time between the first DOCS score -2 to +2 to last DOCS score between -2 and +2 post-fracture reduction
Time Frame
Within 2 hours following intervention
Title
Proportion of time participant adequately sedated during fracture reduction
Description
Proportion of time DOCS score is -2 to +2 during fracture reduction.
Time Frame
Within 2 hours following intervention
Title
Adverse events
Description
The proportion of participants with adverse effects between groups will be compared. The list of adverse effects was chosen based on known adverse effects associated with ketamine and consensus-based recommendations for reporting for procedural sedation and analgesia in children.
Time Frame
Within 2 hours following intervention
Title
Length of stay due to PSA
Description
Time interval from the first pair of IN sprays to discharge
Time Frame
Within 3 hours of intervention
Title
Duration of procedure
Description
Time of the first pair of IN sprays to the end of cast or splint application
Time Frame
Within 3 hours of intervention
Title
Caregiver satisfaction
Description
Obtained when patient is awake and drinking using a Visual Analog Scale; Parents not wishing to remain in proximity of child for sedation may opt out
Time Frame
Within 2 hours of intervention
Title
Participant satisfaction
Description
Obtained when patient is awake and drinking using a Visual Analog Scale; Satisfaction will only be assessed in children at least eight years of age as the VAS has not been validated in younger children.
Time Frame
Within 2 hours of intervention
Title
Physician satisfaction
Description
Obtained immediately prior to discharge using a Visual Analog Scale
Time Frame
Within 2 hours of intervention
Title
Nurse satisfaction
Description
Obtained immediately prior to discharge using a Visual Analog Scale
Time Frame
Within 2 hours of intervention
Title
Requirement for additional sedative medication
Description
Number of doses and type of adjunctive sedative medication required; Deemed inadequate if additional sedative medication given (for IN ketamine group only)
Time Frame
Within 2 hours of intervention
Title
Analgesic medication
Description
Number of doses and type of analgesic medication required
Time Frame
Within 2 hours of intervention
Title
Pain
Description
Pain scores will be recorded using the FPS-R on arrival and when the child is awake and drinking
Time Frame
Within 2 hours of intervention
Title
Emergence delirium
Description
The proportion of children experiencing emergence delirium will be compared using the Paediatric Anesthesia Emergence Delirium (PAED) scale scored from the video every 5 minutes by an outcome assessor starting when fracture reduction is complete to when awake and drinking
Time Frame
20 to 80 minutes post-IV intervention
Title
Nasal irritation
Description
Measured using the Faces Pain Scale - Revised when awake and drinking
Time Frame
Within 2 hours following intervention
Title
Successful sedation
Description
Successful sedation - Based on the definition of Bhatt et al., this will be defined as no unpleasant patient recall of the procedure, no resistance or restraint required during the procedure, no permanent sedation-related complication or no sedation-related event requiring abandonment of the procedure.
Defined as: no unpleasant patient recall of the procedure, no resistance or restraint required during the procedure, no permanent sedation-related complication or no sedation-related event requiring abandonment of the procedure.
Defined as no unpleasant recall of procedure, no resistance or restraint, no permanent sedation related complication, no sedation-related event requiring abandonment of procedure
Time Frame
Within 2 hours following intervention
Title
Adjunctive IV therapy
Description
Other reasons for IV insertion (analgesia, anxiolysis, fluids, etc.)
Time Frame
Within 2 hours following intervention
Title
Number of IN sprays received / Intended number of sprays
Description
Number of IN sprays received / Intended number of sprays
Time Frame
Within 2 hours following intervention
Title
Number of IV attempts
Description
Number of IV attempts and time to IV insertion Number of IV attempts
Time Frame
Within 2 hours following intervention
Title
Time to IV insertion
Description
Time from first breakage of skin to establishment of successful flow with a flush
Time Frame
Within 2 hours following intervention
10. Eligibility
Sex
All
Minimum Age & Unit of Time
4 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age 4 -17 years
Up to 80 kg
Presenting the paediatric emergency department
Require a closed reduction by procedural sedation and analgesia
Acute (=< 48 hours) distal radius and/or ulna fracture that is angulated with or without displacement
No more than 0.5 cm shortening in either the radius or ulna (not both)
Exclusion Criteria:
Previous hypersensitivity reaction to ketamine
Globe rupture
Traumatic brain injury with intracranial hemorrhage
History of uncontrolled hypertension
Nasal bone deformity
Duration of reduction expected to be greater than 20 minutes
Poor English or French fluency in the absence of a native language interpreter
American Society of Anesthesiologists (ASA) class of 3 or greater
Previous sedation with ketamine within 24 hours
Previous diagnosis of schizophrenia or psychosis based on DSM-V criteria
Pregnancy
Neuro-cognitive impairment that precludes informed consent, assent, or ability to self-report pain and satisfaction
Multi-limb trauma
Hemodynamic compromise
Glasgow coma score < 15
Fracture is comminuted
Fracture is associated with a dislocation
Hematoma block at index visit
Unilateral or bilateral nasal obstruction (due to infectious or allergic rhinitis, nasal polyps, septal hematoma, or septal deviation)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Naveen Poonai, MD
Phone
5196858500
Ext
52011
Email
naveen.poonai@lhsc.on.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Cindy Langford, RN
Phone
5196858500
Ext
52011
Email
cindy.langford@lhsc.on.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Naveen Poonai, MD
Organizational Affiliation
Western University
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
32300671
Citation
Heath A, Offringa M, Pechlivanoglou P, Rios JD, Klassen TP, Poonai N, Pullenayegum E; KidsCAN PERC Innovative Paediatric Clinical Trials Team. Determining a Bayesian predictive power stopping rule for futility in a non-inferiority trial with binary outcomes. Contemp Clin Trials Commun. 2020 Apr 8;18:100561. doi: 10.1016/j.conctc.2020.100561. eCollection 2020 Jun.
Results Reference
derived
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Intranasal Ketamine for Procedural Sedation
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