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Bone FracturesPhase 3INKNCT02828566

Intranasal Ketamine for Procedural Sedation

A Phase 3 study testing IN ketamine, IV ketamine and IN saline 0.9% in people with Bone Fractures and Dislocations, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 4 to 17 years
Conditions the study is for
Bone Fractures, Dislocations
What is being tested?
IN ketamine, IV ketamine and IN saline 0.9%
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
470 participants
Where
No sites listed yet
Study dates
Oct 2017to Feb 2019
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 4 to 17 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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)

Who cannot join

  • 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
Show all 19Show fewer
  • 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)

Trial locations and contacts

No sites are listed yet.

About this study

Official title: Intranasal Ketamine Versus Intravenous Ketamine for Procedural Sedation in Children: a Multi-centre Randomized Controlled Non-inferiority Trial

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).

Read the 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

Being tested
IN ketamine, IV ketamine, IN saline 0.9%, IV saline 0.9%
Medical subject headings
Fractures, Bone, Joint Dislocations

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IN ketamineDrug

    Also called ketamine hydrochloride

    Intranasal ketamine 100 mg/mL solution (10 mg/kg, maximum 800 mg)

  • IV ketamineDrug

    Also called ketamine hydrochloride

    Intravenous ketamine 50 mg/mL solution (1 to 1.5 mg/kg, maximum 120 mg)

  • IN saline 0.9%Drug

    Intranasal 0.9% normal saline

  • IV saline 0.9%Drug

    Intravenous 0.9% normal saline

Study groups in NCT02828566
Study groupRoleWhat they receive
IN ketamine and IV salineExperimentalKetamine, 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
Receives: Drug: IN ketamine; Drug: IV saline 0.9%
IV ketamine and IN salineActive comparatorKetamine, 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
Receives: Drug: IV ketamine; Drug: IN saline 0.9%

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Adequacy of sedation

    Proportion with DOCS score -2 to +2 for duration of fracture reduction

    Measured: Duration of fracture reduction

Secondary outcomes (21)
  1. Depth of sedation

    Score using Pediatric Sedation State Scale

    Measured: Duration of fracture reduction

  2. Onset of adequate sedation

    Time interval from first IN sprays to first DOCS score between -2 and +2 in minutes

    Measured: Within 1 hour following intervention

  3. 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

    Measured: Within 2 hours following intervention

  4. Proportion of time participant adequately sedated during fracture reduction

    Proportion of time DOCS score is -2 to +2 during fracture reduction.

    Measured: Within 2 hours following intervention

  5. 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.

    Measured: Within 2 hours following intervention

  6. Length of stay due to PSA

    Time interval from the first pair of IN sprays to discharge

    Measured: Within 3 hours of intervention

  7. Duration of procedure

    Time of the first pair of IN sprays to the end of cast or splint application

    Measured: Within 3 hours of intervention

  8. 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

    Measured: Within 2 hours of intervention

  9. 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.

    Measured: Within 2 hours of intervention

  10. Physician satisfaction

    Obtained immediately prior to discharge using a Visual Analog Scale

    Measured: Within 2 hours of intervention

  11. Nurse satisfaction

    Obtained immediately prior to discharge using a Visual Analog Scale

    Measured: Within 2 hours of intervention

  12. 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)

    Measured: Within 2 hours of intervention

  13. Analgesic medication

    Number of doses and type of analgesic medication required

    Measured: Within 2 hours of intervention

  14. Pain

    Pain scores will be recorded using the FPS-R on arrival and when the child is awake and drinking

    Measured: Within 2 hours of intervention

  15. 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

    Measured: 20 to 80 minutes post-IV intervention

  16. Nasal irritation

    Measured using the Faces Pain Scale - Revised when awake and drinking

    Measured: Within 2 hours following intervention

  17. 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

    Measured: Within 2 hours following intervention

  18. Adjunctive IV therapy

    Other reasons for IV insertion (analgesia, anxiolysis, fluids, etc.)

    Measured: Within 2 hours following intervention

  19. Number of IN sprays received / Intended number of sprays

    Number of IN sprays received / Intended number of sprays

    Measured: Within 2 hours following intervention

  20. Number of IV attempts

    Number of IV attempts and time to IV insertion Number of IV attempts

    Measured: Within 2 hours following intervention

  21. Time to IV insertion

    Time from first breakage of skin to establishment of successful flow with a flush

    Measured: Within 2 hours following intervention

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Jul 2016 (estimated)
  2. Study startOct 2017 (estimated)
  3. Primary completionJan 2019 (estimated)
  4. Study completionFeb 2019 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
470 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02828566
Sponsor's protocol ID
106550
Acronym
INK
Status last verified
Mar 2017
First submitted
30 Jun 2016
Last updated
29 Aug 2017
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

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.

    PubMed 32300671

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing IN ketamine, IV ketamine and IN saline 0.9% in people with Bone Fractures and Dislocations, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 29 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Naveen Poonai, MD (5196858500 ext. 52011, naveen.poonai@lhsc.on.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Adequacy of sedation (time frame: Duration of fracture reduction). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02828566, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Aug 2017.

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