Intranasal Dexmedetomidine Plus Ketamine for Procedural Sedation

Study Details

Brief summary:

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).

Conditions

Fracture

Dislocation

Study ID

NCT04195256

Start date

Mar 11, 2020

Status verified date

Nov, 2024

Completion date

Dec, 2026

Anticipated

Primary completion date

Dec, 2026

Anticipated

Eligibility Criteria

Sex: All

Age: 2 - 17

Healthy Volunteers: Not accepted

INCLUSION CRITERIA

General Criteria

1. Provision of signed and dated informed consent form
2. Stated willingness to comply with all study procedures and availability for the duration of the study
3. Deemed by treating physician to require procedural sedation

Specific criteria

1. Children presenting to the paediatric EDs of participating sites age 2-17 years
2. Weighing up to and including 100 kg
3. One of the following injuries:

Closed forearm fracture
Metacarpal or phalangeal fracture
Dislocation of a shoulder or elbow
Type II supracondylar fracture

4. Expected to not require more than one dose of IV sedative medication if they were not in the trial (as determined by the procedure physician and not including cast or splint application).
5. Both nares are fully patent
6. Physician plans to sedate patient

EXCLUSION CRITERIA

1. Previous hypersensitivity reaction to ketamine or dexmedetomidine including rash, difficulty breathing, hypotension, apnea, or laryngospasm;
2. Suspected globe rupture;
3. Concomitant traumatic brain injury with intracranial hemorrhage;
4. Uncontrolled hypertension;
5. Nasal bone deformity or septal deviation;
6. Poor English or French fluency in the absence of native language interpreter;
7. American Society of Anesthesiologists (ASA) class 3 or greater;
8. Previous diagnosis of schizophrenia or active psychosis as per the treating physician
9. Neuro-cognitive impairment that precludes informed consent, assent, or ability to self-report pain and satisfaction;
10. More than one fracture or dislocation requiring reduction;
11. Hemodynamic compromise as per the treating physician;
12. Glasgow coma score < 15;
13. Previous sedation with ketamine or hematoma block within 24 hours;
14. Fracture is comminuted or associated with a dislocation;
15. Participant has undergone a hematoma block within 24 hours;
16. Obstructive sleep apnea
17. Previous enrollment in the trial;
18. Suspected pregnancy
19. Congenital heart disease or known cardiac dysrhythmia
20. Known or suspected hepatic impairment
21. Known renal insufficiency
22. Uncorrected mineralocorticoid deficiency

Study Design

Enrollment

400 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: IN Ketodex (D4K2)

Dexmedetomidine (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

experimental: IN Ketodex (D3K3)

Dexmedetomidine (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

experimental: IN Ketodex (D2K4)

Dexmedetomidine (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

active comparator: IV Ketamine

Ketamine, 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

Interventions

IN Ketodex (D4K2)

Dexmedetomidine (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)

Dexmedetomidine (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)

Dexmedetomidine (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

Ketamine, 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

Primary outcome measure

Adequate sedation [ Time Frame: Through study completion in the ED (4 hours) ]

Central Contacts and Locations

Central contacts

Naveen Poonai, MD

5196858500 naveen.poonai@lhsc.on.ca

Kamary Coriolano, PhD

5196858500 kamary.coriolanodasilva@lhsc.on.ca

Locations

London Health Sciences Centre

Recruiting

London, Ontario, Canada, N6A5W9

Contacts

Naveen Poonai, MD

5196945309 naveen.poonai@lhsc.on.ca

Dexmedetomidine & KetamineIntranasal Dexmedetomidine Plus Ketamine for Procedural Sedation

Study Details

Eligibility Criteria

Study Design

Interventions and Outcome Measures

Central Contacts and Locations

More Information