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RecruitingNCT04195256KetodexUpdated Nov 5, 2024

Intranasal Dexmedetomidine Plus Ketamine for Procedural Sedation

A Phase 2/3 interventional study of IN Ketodex (D4K2) and IN Ketodex (D3K3) in Fracture and Dislocation, sponsored by Naveen Poonai. Recruiting at 6 sites in Canada. Open to participants aged 2 Years to 17 Years. Per ClinicalTrials.gov, last updated 2024-11-05.

Sponsored by Naveen Poonai · Phase 2/3, Interventional, and Treatment

From the registry’s dates

  • Started Mar 2020; still recruiting 6 years 8 months later.
Phase
Phase 2/3
Study type
Interventional
Enrollment
400
Allocation
Randomized
Ages
2 Years to 17 Years
Sex
All
01

Study 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).

Read the detailed description

Intranasal medications may offer a technically easier and pain-free approach to procedural sedation (PSA); one that may have widespread applicability in patients with needle-phobia, difficult IV access, resource-limited settings, or when experience placing an IV is limited. Although IN ketamine has been found to be effective for fracture pain, procedural pain, anesthetic pre-induction, and diagnostic imaging, a recent shortage of this agent in the highest concentration of 100 mg/mL has severely limited out ability to study its effectiveness and consequent clinical uptake. Our research team conducted three systematic reviews of randomized trials of IN ketamine and IN dexmedetomidine in children undergoing painful procedures. The latter review included 18 trials (n=2128) of children age 1 month to 14 years. Our review found that IN dexmedetomidine, dosed from 1-4 mcg/kg, was well tolerated and superior to conventional sedatives (midazolam and chloral hydrate) in providing adequate sedation to 525/669 (78.5%) children. A number of studies found that IN dexmedetomidine was in fact superior to IN ketamine. Surendar et al. found that IN dexmedetomidine at 1.5 mcg/kg facilitated successful sedation in 18/21 (86%) of children undergoing dental procedures and was more effective than IN ketamine 5 mg/kg. Gyanesh et al. found that the proportion of children with satisfactory IV sedation was greater with IN dexmedetomidine 1 mcg/kg compared to IN ketamine 5 mg/kg [47/52 (90%) versus 43/52 (83%), respectively]. Mostafa et al. found that IN dexmedetomidine 1 mcg/kg was more effective at facilitating caregiver separation than IN ketamine 5 mg/kg or IN midazolam 0.2 mg/kg [30/32 (92%) versus 22/32 (69%) versus 28/32 (88%), respectively]. Moreover, a combination of dexmedetomidine and ketamine appeared to be superior than either agent alone. Qiao et al. found that IN dexmedetomidine 2 mcg/kg and oral ketamine 3 mg/kg in children undergoing IV insertion was superior to both IN dexmedetomidine 2.5 mcg/kg and oral ketamine 6 mg/kg alone (80.1% versus 47.6% versus 68.3%, respectively). Bhat et al. found that a combination of IN dexmedetomidine 1 mcg/kg and IN ketamine 2 mg/kg versus IN dexmedetomidine 1 mcg/kg alone facilitated greater acceptance of face mask (67% versus 52%, respectively) and greater tolerance of caregiver separation (93% versus 89%, respectively) (38). We also found evidence that higher doses of IN dexmedetomidine were more effective. More specifically, at the higher end of the dosing range (1-4 mcg/kg), IN dexmedetomidine 3 mcg/kg was superior to IN ketamine 7 mg/kg; providing adequate sedation to 25/29 (86.3%) versus 23/29 (79.4%) of children undergoing IV insertion, respectively. A dose-finding study of IN dexmedetomidine in children \< 3 years who were post-operative from cardiac surgery and were undergoing transthoracic echocardiography found an optimal median effective dose of 3.3 mcg/kg (range 2.72-3.78 mcg/kg). Taken together, our review suggests that the most effective and tolerable intranasal agent for procedural sedation for fracture reduction is a combination of IN dexmedetomidine 4 mcg/kg and IN ketamine 2-3 mg/kg. There is ample and ongoing evidence of suboptimal management for procedural pain in children, a high frequency of orthopedic injuries requiring IV placement for PSA, and a lack of evidence to support the use of strategies that reduce the pain of IVs. However, there are no studies that have shown the effectiveness of IN ketamine for fracture reduction in children. In order to provide robust evidence supporting an alternate approach that precludes the need for an IV in children undergoing PSA, the investigators propose a study to answer the important research question: In children presenting to the ED with an orthopedic injury requiring PSA, does IN Ketodex provide as effective sedation as IV ketamine?

02

Conditions studied

  • Fracture
  • Dislocation
03

In context

Fractures, Bone

723 studies on the registry are indexed under Fractures, Bone; 114 are open to participants now.

This study's planned enrollment of 400 is above the median of 80 across 458 interventional studies indexed under Fractures, Bone.

Browse Fractures, Bone studies →

Lead sponsor

Naveen Poonai is the lead sponsor of 3 studies on the registry; 2 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
2 Years to 17 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

General Criteria

  1. Provision of signed and dated 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

EXCLUSION CRITERIA

  1. Previous 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. (ASA) class 3 or greater;
  8. Previous diagnosis of schizophrenia or active psychosis as per the treating physician
  9. Neuro-cognitive impairment that precludes , 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
Terms in these criteria, in plain language(3)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Hypersensitivity

An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.

ASA physical status

The anaesthetists’ scale of health before surgery: I is healthy, II has a mild illness that is under control, III a severe one, IV a severe illness that is a constant threat to life. V and VI are used for the critically ill and for organ donors.

05

Study design

Phase
Phase 2 / Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
400 participants (estimated)

Study 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

    Drug: IN Ketodex (D4K2)

  • 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

    Drug: IN Ketodex (D3K3)

  • 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

    Drug: IN Ketodex (D2K4)

  • 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

    Drug: IV Ketamine

Interventions

  • DrugIN 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

    Also known as: Ketamine+Dexmedetomidine

  • DrugIN 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

    Also known as: IN Ketodex II

  • DrugIN 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

    Also known as: IN Ketodex III

  • DrugIV 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

    Also known as: Ketamine hydrochloride

06

What researchers measure

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-discharge

Other 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)

  5. Volume of IN intervention received / Volume of IN intervention intended

    Volume of IN intervention received / Volume of IN intervention intended

    Time frame: Through study completion in the ED (4 hours)

  6. Adjunctive IV therapy and medications

    The number of participants requiring an IV for therapy unrelated to sedation (eg. analgesics, antibiotics, antiemetics, fluids) will be recorded.

    Time frame: Through study completion in the ED (4 hours)

  7. Pre-sedation Pain

    Will be recorded by the research nurse from the participant using the Faces Pain Scale - Revised (FPS-R) immediately prior to the first pair of intranasal sprays

    Time frame: Through study completion in the ED (4 hours)

  8. Patient Preference

    The following question will be posed to the child: "If you were to be put to sleep again for an injury, what would you prefer, an intravenous needle or nasal sprays (choose one)?"

    Time frame: Through study completion in the ED (4 hours)

  9. Exploratory subgroup analyses

    A planned subgroup analyses to determine whether the between group difference in adequacy of sedation is dependent on (i) pain score prior to sedation.

    Time frame: Through study completion in the ED (4 hours)

07

Study locations

1 of 6 sites recruiting
08

References and documents

Publications

  • 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. PubMed 33407719 ↗

Individual participant data

Plan to share: No

09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Started Mar 2020 (actual). Primary completion is estimated for Dec 2026, 81 months after the start.

How these figures are worked out, and which studies are left out of them.

Registered
Aug 15, 2019
First posted
Dec 11, 2019
StartActual
Mar 11, 2020
Primary completionEst.
Dec 2026
CompletionEst.
Dec 2026
Last update
Nov 5, 2024
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Nov 5, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT04195256
Lead sponsor
Naveen Poonai
Responsible party
Naveen Poonai (Sponsor-Investigator/Associate Professor, London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's) — Sponsor-investigator
First posted
Dec 11, 2019
Start date
Mar 11, 2020
Primary completion
Dec 2026 (estimated)
Completion
Dec 2026 (estimated)
Last update
Nov 5, 2024

Study contacts

Naveen Poonai, MD
Contact
naveen.poonai@lhsc.on.ca
5196858500
Kamary Coriolano, PhD
Contact
kamary.coriolanodasilva@lhsc.on.ca
5196858500
Naveen Poonai, MD
principal investigator · Western University

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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