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Intranasal Ketamine for Procedural Sedation (INK)

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ClinicalTrials.gov Identifier: NCT02828566
Recruitment Status : Unknown
Verified March 2017 by Lawson Health Research Institute.
Recruitment status was:  Not yet recruiting
First Posted : July 11, 2016
Last Update Posted : August 29, 2017
Sponsor:
Information provided by (Responsible Party):
Lawson Health Research Institute

Tracking Information
First Submitted Date  ICMJE June 30, 2016
First Posted Date  ICMJE July 11, 2016
Last Update Posted Date August 29, 2017
Estimated Study Start Date  ICMJE October 2017
Estimated Primary Completion Date January 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 29, 2017)
Adequacy of sedation [ Time Frame: Duration of fracture reduction ]
Proportion with DOCS score -2 to +2 for duration of fracture reduction
Original Primary Outcome Measures  ICMJE
 (submitted: July 7, 2016)
Dartmouth Operative Conditions Scale [ Time Frame: 20 minutes post IV intervention ]
Scored by an outcome assessor of a video every 30 seconds
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 15, 2017)
  • Depth of sedation [ Time Frame: Duration of fracture reduction ]
    Score using Pediatric Sedation State Scale
  • Onset of adequate sedation [ Time Frame: Within 1 hour following intervention ]
    Time interval from first IN sprays to first DOCS score between -2 and +2 in minutes
  • Duration of sedation [ Time Frame: Within 2 hours following intervention ]
    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 [ Time Frame: Within 2 hours following intervention ]
    Proportion of time DOCS score is -2 to +2 during fracture reduction.
  • Adverse events [ Time Frame: Within 2 hours following intervention ]
    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 Frame: Within 3 hours of intervention ]
    Time interval from the first pair of IN sprays to discharge
  • Duration of procedure [ Time Frame: Within 3 hours of intervention ]
    Time of the first pair of IN sprays to the end of cast or splint application
  • Caregiver satisfaction [ Time Frame: Within 2 hours of intervention ]
    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 [ Time Frame: Within 2 hours of intervention ]
    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 [ Time Frame: Within 2 hours of intervention ]
    Obtained immediately prior to discharge using a Visual Analog Scale
  • Nurse satisfaction [ Time Frame: Within 2 hours of intervention ]
    Obtained immediately prior to discharge using a Visual Analog Scale
  • Requirement for additional sedative medication [ Time Frame: Within 2 hours of intervention ]
    Number of doses and type of adjunctive sedative medication required; Deemed inadequate if additional sedative medication given (for IN ketamine group only)
  • Analgesic medication [ Time Frame: Within 2 hours of intervention ]
    Number of doses and type of analgesic medication required
  • Pain [ Time Frame: Within 2 hours of intervention ]
    Pain scores will be recorded using the FPS-R on arrival and when the child is awake and drinking
  • Emergence delirium [ Time Frame: 20 to 80 minutes post-IV intervention ]
    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 [ Time Frame: Within 2 hours following intervention ]
    Measured using the Faces Pain Scale - Revised when awake and drinking
  • Successful sedation [ Time Frame: Within 2 hours following intervention ]
    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 [ Time Frame: Within 2 hours following intervention ]
    Other reasons for IV insertion (analgesia, anxiolysis, fluids, etc.)
  • Number of IN sprays received / Intended number of sprays [ Time Frame: Within 2 hours following intervention ]
    Number of IN sprays received / Intended number of sprays
  • Number of IV attempts [ Time Frame: Within 2 hours following intervention ]
    Number of IV attempts and time to IV insertion Number of IV attempts
  • Time to IV insertion [ Time Frame: Within 2 hours following intervention ]
    Time from first breakage of skin to establishment of successful flow with a flush
Original Secondary Outcome Measures  ICMJE
 (submitted: July 7, 2016)
  • Onset of adequate sedation [ Time Frame: Within 1 hour following intervention ]
    Time interval from first IN spray to DOCS score between -2 and +2 in minutes
  • Duration of sedation [ Time Frame: Within 2 hours following intervention ]
    This will be defined as the duration of time between the first DOCS score between -2 to +2 post-intervention to the last DOCS score between -2 and +2 post-procedure.
  • Adverse events [ Time Frame: Within 2 hours following intervention ]
    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 [ Time Frame: Within 3 hours of intervention ]
    This will be described as the time interval from being checked in by a nurse once in an ED bed to discharge in minutes
  • Length of stay due to PSA [ Time Frame: Within 3 hours of intervention ]
    This will be from the time of the first IN spray to discharge in minutes
  • Duration of procedure [ Time Frame: Within 3 hours of intervention ]
    This will be defined as time of first IN spray to the end of cast or splint application .
  • Caregiver satisfaction [ Time Frame: Within 2 hours of intervention ]
    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 [ Time Frame: Within 2 hours of intervention ]
    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 [ Time Frame: Within 2 hours of intervention ]
    Obtained immediately prior to discharge using a Visual Analog Scale
  • Rescue sedation medication [ Time Frame: Within 2 hours of intervention ]
    Number of doses and type of adjunctive sedative medication required
  • Analgesic medication [ Time Frame: Within 2 hours of intervention ]
    Number of doses and type of analgesic medication required
  • Pain [ Time Frame: Within 2 hours of intervention ]
    Pain scores will be recorded using the FPS-R immediately prior to the first IN spray and post administration of the IV intervention when the child is awake and drinking.
  • Emergence delirium [ Time Frame: 20 to 80 minutes post-IV intervention ]
    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
  • Nasal irritation [ Time Frame: Within 2 hours following intervention ]
    The participant's self-reported perception of nasal irritation using five-item Likert scale as has been previously published when the child is awake and able to tolerate oral fluids
  • Successful sedation [ Time Frame: Within 2 hours of following intervention ]
    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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Intranasal Ketamine for Procedural Sedation
Official Title  ICMJE Intranasal Ketamine Versus Intravenous Ketamine for Procedural Sedation in Children: a Multi-centre Randomized Controlled Non-inferiority Trial
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
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
  • Bone Fractures
  • Dislocations
Intervention  ICMJE
  • Drug: IN ketamine
    Intranasal ketamine 100 mg/mL solution (10 mg/kg, maximum 800 mg)
    Other Name: ketamine hydrochloride
  • Drug: IV ketamine
    Intravenous ketamine 50 mg/mL solution (1 to 1.5 mg/kg, maximum 120 mg)
    Other Name: ketamine hydrochloride
  • Drug: IN saline 0.9%
    Intranasal 0.9% normal saline
  • Drug: IV saline 0.9%
    Intravenous 0.9% normal saline
Study Arms  ICMJE
  • Experimental: IN ketamine and IV saline
    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
    Interventions:
    • Drug: IN ketamine
    • Drug: IV saline 0.9%
  • Active Comparator: IV ketamine and IN saline
    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
    Interventions:
    • Drug: IV ketamine
    • Drug: IN saline 0.9%
Publications * 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.

*   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 Unknown status
Estimated Enrollment  ICMJE
 (submitted: August 25, 2017)
470
Original Estimated Enrollment  ICMJE
 (submitted: July 7, 2016)
456
Estimated Study Completion Date  ICMJE February 2019
Estimated Primary Completion Date January 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Age 4 -17 years
  2. Up to 80 kg
  3. Presenting the paediatric emergency department
  4. Require a closed reduction by procedural sedation and analgesia
  5. Acute (=< 48 hours) distal radius and/or ulna fracture that is angulated with or without displacement
  6. No more than 0.5 cm shortening in either the radius or ulna (not both)

Exclusion Criteria:

  1. Previous hypersensitivity reaction to ketamine
  2. Globe rupture
  3. Traumatic brain injury with intracranial hemorrhage
  4. History of uncontrolled hypertension
  5. Nasal bone deformity
  6. Duration of reduction expected to be greater than 20 minutes
  7. Poor English or French fluency in the absence of a native language interpreter
  8. American Society of Anesthesiologists (ASA) class of 3 or greater
  9. Previous sedation with ketamine within 24 hours
  10. Previous diagnosis of schizophrenia or psychosis based on DSM-V criteria
  11. Pregnancy
  12. Neuro-cognitive impairment that precludes informed consent, assent, or ability to self-report pain and satisfaction
  13. Multi-limb trauma
  14. Hemodynamic compromise
  15. Glasgow coma score < 15
  16. Fracture is comminuted
  17. Fracture is associated with a dislocation
  18. Hematoma block at index visit
  19. Unilateral or bilateral nasal obstruction (due to infectious or allergic rhinitis, nasal polyps, septal hematoma, or septal deviation)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 4 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 Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02828566
Other Study ID Numbers  ICMJE 106550
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Lawson Health Research Institute
Study Sponsor  ICMJE Lawson Health Research Institute
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Naveen Poonai, MD Western University
PRS Account Lawson Health Research Institute
Verification Date March 2017

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