Intranasal Dexmedetomidine Plus Ketamine for Procedural Sedation

NCT04195256 | Recruiting Phase 2 DMC

• 1 other identifier: 091819
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 6

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

Outcome Measures

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.

  Through study completion in the ED (4 hours)

Secondary Outcomes (3)

• Length of stay

  Through study completion in the ED (4 hours)

• Time to wakening

  Through study completion in the ED (4 hours)

• Adverse effects

  Through study completion in the ED and up to 72 hours post-discharge

Other Outcomes (9)

• Length of stay due to procedural sedation

  Through study completion in the ED (4 hours)

• Duration of procedure

  Through study completion in the ED (4 hours)

• Caregiver, participant, bedside nurse or respiratory therapist, and physician satisfaction

  Through study completion in the ED (4 hours)

Study Arms (4)

IN Ketodex (D4K2)

EXPERIMENTAL

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

Drug: IN Ketodex (D4K2)

IN Ketodex (D3K3)

EXPERIMENTAL

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

Drug: IN Ketodex (D3K3)

IN Ketodex (D2K4)

EXPERIMENTAL

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

Drug: IN Ketodex (D2K4)

IV Ketamine

ACTIVE COMPARATOR

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

Drug: IV Ketamine

Interventions

IN Ketodex (D4K2) DRUG

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

Also known as: Ketamine+Dexmedetomidine

IN Ketodex (D4K2)

IN Ketodex (D3K3) DRUG

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

Also known as: IN Ketodex II

IN Ketodex (D3K3)

IN Ketodex (D2K4) DRUG

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

Also known as: IN Ketodex III

IN Ketodex (D2K4)

IV Ketamine DRUG

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

Also known as: Ketamine hydrochloride

IV Ketamine

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• General Criteria
• 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
• Specific criteria
• Children presenting to the paediatric EDs of participating sites age 2-17 years
• Weighing up to and including 100 kg
• One of the following injuries:
• Closed forearm fracture
• Metacarpal or phalangeal fracture
• Dislocation of a shoulder or elbow
• Type II supracondylar fracture
• 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).
• Both nares are fully patent
• Physician plans to sedate patient

You may not qualify if:

• 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;
• Nasal bone deformity or septal deviation;
• Poor English or French fluency in the absence of native language interpreter;
• American Society of Anesthesiologists (ASA) class 3 or greater;
• Previous diagnosis of schizophrenia or active psychosis as per the treating physician
• Neuro-cognitive impairment that precludes informed consent, assent, or ability to self-report pain and satisfaction;
• More than one fracture or dislocation requiring reduction;
• Hemodynamic compromise as per the treating physician;
• Glasgow coma score \< 15;
• Previous sedation with ketamine or hematoma block within 24 hours;
• Fracture is comminuted or associated with a dislocation;
• Participant has undergone a hematoma block within 24 hours;

Sponsors & Collaborators

• Naveen Poonai: lead

Study Sites (6)

Stollery Children's Hospital

Edmonton, Alberta, Canada

COMPLETED

BC Children's Hospital

Vancouver, British Columbia, Canada

COMPLETED

McMaster Children's Hospital

Hamilton, Ontario, Canada

COMPLETED

London Health Sciences Centre

London, Ontario, N6A5W9, Canada

RECRUITING

Children's Hospital of Eastern Ontario

Ottawa, Ontario, Canada

WITHDRAWN

Winnipeg Children's Hospital

Winnipeg, Ontario, Canada

COMPLETED

Related Publications (1)

• Heath A, Rios JD, Pullenayegum E, Pechlivanoglou P, Offringa M, Yaskina M, Watts R, Rimmer S, Klassen TP, Coriolano K, Poonai N; PERC-KIDSCAN Ketodex Study Group. The intranasal dexmedetomidine plus ketamine for procedural sedation in children, adaptive randomized controlled non-inferiority multicenter trial (Ketodex): a statistical analysis plan. Trials. 2021 Jan 6;22(1):15. doi: 10.1186/s13063-020-04946-3.

  PMID: 33407719 DERIVED

MeSH Terms

Conditions

Fractures, Bone; Joint Dislocations

Interventions

Ketamine

Condition Hierarchy (Ancestors)

Wounds and Injuries; Joint Diseases; Musculoskeletal Diseases

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Naveen Poonai, MD

  Western University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Naveen Poonai, MD

CONTACT

5196858500; naveen.poonai@lhsc.on.ca

Kamary Coriolano, PhD

CONTACT

5196858500; kamary.coriolanodasilva@lhsc.on.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-dummy
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator/Associate Professor

Model Details: Adaptive, multi-centre, two-arm, randomized, blinded, double-dummy, controlled, parallel group, non-inferiority, phase II/III trial

Study Record Dates

• First Submitted: August 15, 2019
• First Posted: December 11, 2019
• Study Start: March 11, 2020
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: November 5, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (6)