Intranasal Ketamine for Procedural Sedation

Bone Fractures Clinical Trial

— INK  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02828566
• Other study ID #: 106550
• Status: Not yet recruiting
• Phase: Phase 3
• First received: June 30, 2016
• Last updated: August 25, 2017
• Start date: October 2017
• Est. completion date: February 2019

Study information

• Verified date: March 2017
• Source: Lawson Health Research Institute
• Contact: Naveen Poonai, MD
• Phone: 5196858500
• Email: naveen.poonai[@]lhsc.on.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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).

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

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 470
• Est. completion date: February 2019
• Est. primary completion date: January 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years to 17 Years

Eligibility

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)

Related Conditions & MeSH terms

• Bone Fractures
• Dislocations
• Fractures, Bone

Intervention

Drug:
• IN ketamine
Intranasal ketamine 100 mg/mL solution (10 mg/kg, maximum 800 mg)
• IV ketamine
Intravenous ketamine 50 mg/mL solution (1 to 1.5 mg/kg, maximum 120 mg)
• IN saline 0.9%
Intranasal 0.9% normal saline
• IV saline 0.9%
Intravenous 0.9% normal saline

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Lawson Health Research Institute

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adequacy of sedation	Proportion with DOCS score -2 to +2 for duration of fracture reduction	Duration of fracture reduction
Secondary	Depth of sedation	Score using Pediatric Sedation State Scale	Duration of fracture reduction
Secondary	Onset of adequate sedation	Time interval from first IN sprays to first DOCS score between -2 and +2 in minutes	Within 1 hour following intervention
Secondary	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	Within 2 hours following intervention
Secondary	Proportion of time participant adequately sedated during fracture reduction	Proportion of time DOCS score is -2 to +2 during fracture reduction.	Within 2 hours following intervention
Secondary	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.	Within 2 hours following intervention
Secondary	Length of stay due to PSA	Time interval from the first pair of IN sprays to discharge	Within 3 hours of intervention
Secondary	Duration of procedure	Time of the first pair of IN sprays to the end of cast or splint application	Within 3 hours of intervention
Secondary	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	Within 2 hours of intervention
Secondary	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.	Within 2 hours of intervention
Secondary	Physician satisfaction	Obtained immediately prior to discharge using a Visual Analog Scale	Within 2 hours of intervention
Secondary	Nurse satisfaction	Obtained immediately prior to discharge using a Visual Analog Scale	Within 2 hours of intervention
Secondary	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)	Within 2 hours of intervention
Secondary	Analgesic medication	Number of doses and type of analgesic medication required	Within 2 hours of intervention
Secondary	Pain	Pain scores will be recorded using the FPS-R on arrival and when the child is awake and drinking	Within 2 hours of intervention
Secondary	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	20 to 80 minutes post-IV intervention
Secondary	Nasal irritation	Measured using the Faces Pain Scale - Revised when awake and drinking	Within 2 hours following intervention
Secondary	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	Within 2 hours following intervention
Secondary	Adjunctive IV therapy	Other reasons for IV insertion (analgesia, anxiolysis, fluids, etc.)	Within 2 hours following intervention
Secondary	Number of IN sprays received / Intended number of sprays	Number of IN sprays received / Intended number of sprays	Within 2 hours following intervention
Secondary	Number of IV attempts	Number of IV attempts and time to IV insertion Number of IV attempts	Within 2 hours following intervention
Secondary	Time to IV insertion	Time from first breakage of skin to establishment of successful flow with a flush	Within 2 hours following intervention