Intranasal Dexmedetomidine Plus Ketamine for Procedural Sedation
Trial statusRecruiting
Trial phasePhase 2, Phase 3
Trial typeInterventional
Biological sexAll
Age2-17
SponsorNaveen Poonai
About this trial
Orthopedic injuries comprise more than 10% of ED visits in children and 25 to 50% of children will sustain a fracture before age 16 years. Distal radius fractures account for 20-32% of fractures in children, making them the most common fracture type. Between 20 and 40% of extremity fractures in children require a closed reduction, often necessitating procedural sedation and analgesia (PSA). Intravenous (IV) ketamine is the most commonly used sedative agent used to perform a closed reduction. However, children rate IV insertion as the most painful hospital experience, second only to the injury itself. IV insertion can be more technically difficult in children because of smaller veins and lack of cooperation, often leading to multiple IV attempts. A combination of intranasal (IN) dexmedetomidine plus ketamine (IN Ketodex) may provide effective sedation for children undergoing a closed reduction without the distress and pain related to IV insertion. A less painful experience has been found to correlate with child satisfaction which may reduce caregiver anxiety and improve the therapeutic relationship with the health care team. This study is a multi-centre, two-arm, randomized, blinded, controlled, non-inferiority trial designed to test the hypothesis that IN Ketodex is non-inferior to intravenous (IV) ketamine with respect to depth of sedation as measured using the Pediatrics Sedation State Scale (PSSS).
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Provision of signed and dated informed consent form
Stated willingness to comply with all study procedures and availability for the duration of the study
Deemed by treating physician to require procedural sedation
Children presenting to the paediatric EDs of participating sites age 2-17 years
Disqualifiers
Previous hypersensitivity reaction to ketamine or dexmedetomidine including rash, difficulty breathing, hypotension, apnea, or laryngospasm;
Suspected globe rupture;
Concomitant traumatic brain injury with intracranial hemorrhage;
Uncontrolled hypertension;
Trial design
Design model
Parallel
Treatments tested in this trial
IN Ketodex (D4K2)
DrugDexmedetomidine (Pfizer, Kirkland, Quebec), single-dose, 4 mcg/kg (0.04 mL/kg) of 100 mcg/mL solution, maximum of 200 mcg (2 mL) THEN Ketamine (Sandoz, Mississauga, Ontario), single dose, 2 mg/kg (0.04 mL/kg) of 50 mg/mL solution, maximum of 200 mg (4 mL) (D4K2), both delivered intranasally using a mucosal atomizer device (MAD) and divided to both nares AND 0.9% normal saline 0.03 mL/kg delivered intravenously to a maximum of 2 mL
IN Ketodex (D3K3)
DrugDexmedetomidine (Pfizer, Kirkland, Quebec), single-dose, 3 mcg/kg (0.03 mL/kg) of 100 mcg/mL solution, maximum of 200 mcg (2 mL) THEN Ketamine (Sandoz, Mississauga, Ontario), single dose, 3 mg/kg (0.06 mL/kg) of 50 mg/mL solution, maximum of 300 mg (6 mL) (D3K3), both delivered intranasally using a mucosal atomizer device (MAD) and divided to both nares AND 0.9% normal saline 0.03 mL/kg delivered intravenously to a maximum of 2 mL
IN Ketodex (D2K4)
DrugDexmedetomidine (Pfizer, Kirkland, Quebec), single-dose, 2 mcg/kg (0.02 mL/kg) of 100 mcg/mL solution, maximum of 200 mcg (2 mL) THEN Ketamine (Sandoz, Mississauga, Ontario), single dose, 4 mg/kg (0.08 mL/kg) of 50 mg/mL solution, maximum of 400 mg (8 mL) (D2K4), both delivered intranasally using a mucosal atomizer device (MAD) and divided to both nares AND 0.9% normal saline 0.03 mL/kg delivered intravenously to a maximum of 2 mL
IV Ketamine
DrugKetamine, single dose, 1.5 mg/kg (0.03 mL/kg) of 50 mg/mL solution delivered intravenously, to a maximum of 100 mg (2 mL) AND two aliquots of 0.9% normal saline in 3 possible combinations: (i) 0.04 mL/kg (max 2 mL) then 0.04 mL/kg (max 4 mL) (placebo D4K2), (ii) 0.03 mL/kg (max 2 mL) then 0.06 mL/kg (max 6 mL) (placebo D3K3), (iii) 0.02 mL/kg (max 2 mL) then 0.08 mL/kg (max 8 mL) (placebo D2K4), delivered intranasally using a MAD and divided to both nares
Treatment groups
400 Participants
are divided into 4 treatment groupsGroup A: IN Ketodex (D4K2)Experimental treatment 1 intervention
Group B: IN Ketodex (D3K3)Experimental treatment 1 intervention
Group C: IN Ketodex (D2K4)Experimental treatment 1 intervention
Group D: IV KetamineActive comparator 1 intervention
Trial outcomes
Primary outcomes
1
Adequate sedation
Adequate is defined as fulfillment of all three of the following criteria: (i) A Pediatric Sedation State Scale (PSSS) score of 2 or 3 for the duration of the procedure (defined for closed reduction as the interval of time from the first application of traction or manipulation of the injured limb for the purpose of anatomical realignment to the last application of a realigning force). The PSSS is scored from 0 to 5 in discrete integer values every 15 seconds. A score of 4 or 5 indicates under-sedation and a score of 0 or 1 indicates over sedation. (ii) No additional medication is given during the procedure for the purpose of sedation. (iii) The patient did not actively resist, cry, or require physical restraint for completion of the closed reduction.
Time frame
Through study completion in the ED (4 hours)Secondary outcomes
1
Length of stay
Defined as the time recorded in the medical record between triage and discharge.
Time frame
Through study completion in the ED (4 hours)2
Time to wakening
This will be defined as the duration of time between the first pair of IN sprays and the first PSSS score of \> 3 post-closed reduction.
Time frame
Through study completion in the ED (4 hours)3
Adverse effects
Adverse effects as defined by Health Canada reporting standards
Time frame
Through study completion in the ED and up to 72 hours post-dischargeOther outcomes
1
Length of stay due to procedural sedation
Defined as the time interval from the first pair of IN sprays/IV dose to discharge, reflective of the time difference associated with different routes of administration.
Time frame
Through study completion in the ED (4 hours)2
Duration of procedure
Defined as time of the first pair of IN sprays to the end of cast or splint application (closed reduction) in minutes
Time frame
Through study completion in the ED (4 hours)3
Caregiver, participant, bedside nurse or respiratory therapist, and physician satisfaction
Satisfaction will be measured using a visual analog scale (VAS) when the participant is deemed ready for discharge. The following questions will be posed: How satisfied were you with your child's sedation? (Caregiver if at bedside), How happy were you with your sleep? (Participant), or How satisfied were you with the level of sedation in your patient? (Sedating physician \& nurse/respiratory therapist as per who is at bedside).
Time frame
Through study completion in the ED (4 hours)4
Nasal irritation
Discomfort associated with nasal sprays will be assessed by the research nurse using the Faces Pain Scale -Revised (FPS-R) when the participant is deemed ready for discharge. The FPS-R is a self-report measure scored as either 0,2,4,6,8,10, with increasing numbers indicating greater pain.
Time frame
Through study completion in the ED (4 hours)Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Naveen Poonai
Lead sponsor
London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor institution
Source ClinicalTrials.gov