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Trial registered on ANZCTR


Registration number
ACTRN12612000012875
Ethics application status
Approved
Date submitted
19/12/2011
Date registered
4/01/2012
Date last updated
13/03/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
Intranasal ketamine for moderate to severe pain in children- a dose finding study.
Scientific title
A dose-finding study assessing the effectiveness of sub-dissociative doses of intranasal ketamine in the treatment of moderate to severe acute pain in the emergency department in children. Part One of a two-part study protocol.
Secondary ID [1] 279632 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
acute pain 285432 0
musculoskeletal injury 285467 0
Condition category
Condition code
Anaesthesiology 285611 285611 0 0
Pain management
Injuries and Accidents 285649 285649 0 0
Other injuries and accidents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A single dose of intranasal ketamine (0.7mg/kg) will be administered to children aged 3 to 13 years and less than 50kg in weight, presenting to the emergency department with a musculoskeletal injury and verbal pain score of 6 or greater out of 10.

A second dose of 0.5 mg/kg will be administered 15 minutes later if the patient requests further analgesia or there has not been an appreciable drop in pain score (greater than or equal to 3 out of 10)

An analysis will be undertaken after 30 patients to assess response to analgesia and/or presence of sedation. The dose of ketamine will be adjusted up or down depending on response in these first 30 patients.

If patients do not attain a drop in pain score of 3/10 or greater at 30 minutes with the initial dosing regimen, the initial dose of ketamine will be increased to 1 mg/kg and admnistered to another 30 patients. Data will then be analysed for this dose.

OR

If the patients attain adequate analgesia (pain score fall greater than or equal to 3/10) but show signs of significant sedation, the initial dose of ketamine will be reduced to 0.5mg/kg for the second 30 patients followed by analysis of the data for this second cohort of patients.

The second dose of ketamine at t=15 minutes (if required) will remain at 0.5mg/kg
Intervention code [1] 283912 0
Treatment: Drugs
Comparator / control treatment
Nil
Control group
Uncontrolled

Outcomes
Primary outcome [1] 286176 0
Mean change in Visual Analog Scale pain score from pre-administration (T0) to 30 minutes post-administration (T30)
Timepoint [1] 286176 0
30 minutes post-administration of ketamine
Secondary outcome [1] 295305 0
a) Mean change in Visual Analog Scale pain score from pre-administration (T0) to 15 minutes (T15) and 60 minutes (T60) post-administration.
Timepoint [1] 295305 0
15 and 60 minutes after ketamine administration
Secondary outcome [2] 295306 0
b) Percentage responding to each description of change in pain severity (a lot better, a little better, the same, a little worse, a lot worse)
Timepoint [2] 295306 0
T 15, T30, T60 minutes
Secondary outcome [3] 295307 0
c) Percentage requiring an additional dose of ketamine
Timepoint [3] 295307 0
T15 minutes
Secondary outcome [4] 295308 0
d) Percentage responding to each description of satisfaction with amount of analgesia experienced (satisfied, not satisfied, uncertain)
Timepoint [4] 295308 0
T15, T30, T60.
Secondary outcome [5] 295309 0
e) Percentage in which study termination was required and the reason for this:

i) requiring additional analgesia such as extra ketamine or a different analgesic.

ii) other (eg adverse effects or interference of study requirements with necessary therapeutic interventions)
Timepoint [5] 295309 0
at T15, T30, T60
Secondary outcome [6] 295310 0
f) Adverse event profile, specifically including:

i) Observed level of sedation using the Ramsay Sedation Scale (anxious/restless/both, cooperative/orientated/tranquil, respond to commands, brisk response to stimulus, sluggish response to stimulus, no response to stimulus).

ii) Self-reported opinion on level of sedation
iii) Local adverse effects: presence of nasal irritation, bleeding or any local effects reported by the patient.

iv) Systemic adverse effects: changes in vital signs (tachycardia, hyper/hypotension), hallucinations (visual or other).

v) Suspected allergic reaction (incl type)


vi) Any other
Timepoint [6] 295310 0
T15, T30, T60

Eligibility
Key inclusion criteria
Children aged three to 13 years and under 50kg body weight

Musculoskeletal injury to upper and/or lower limbs

Visual analog pain score greater than or equal to 6/10 on the standard 11-point verbal rating scale (0 = none, 10 = worst pain imaginable) and patient would normally be considered for intranasal fentanyl administration.

Use of simple analgesia such as paracetamol or ibuprofen or inhalational methoxyflurane during ambulance transport are not exclusion criteria
Minimum age
3 Years
Maximum age
13 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Inability to gain informed consent from parent or guardian

Prior administration of parenteral or intranasal analgesics (morphine, fentanyl)

Prior administration of oral opioid analgesia (oxycodone, codeine)

Allergy to ketamine

Aberrant nasal anatomy

Acute or chronic nasal problems or nasal trauma that may preclude adequate administration or absorption of intranasal medication.

Presence of multiple trauma or injuries.

Sustained a head injury with loss of consciousness.
Presence of cognitive impairment.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
In general, patients who are eligible for this study are triaged as Australasian Triage Scale (ATS) Category 2 because it is felt that they need analgesia within 10 minutes.

The ED triage nurse will notify the nominated Paediatric ED ‘Cat 2 doctor’ in the usual way. (Note: At the study ED, both the Cat 2 doctor and the ED Consultant In Charge (CIC) receive a pager notification of the arrival of a Category 2 patient (with whatever diagnosis), and so are usually aware of such patients prior to their reaching an ED cubicle.

The Cat 2 doctor will perform a rapid assessment of the patient in the usual way, which during the study period will include consideration of the study inclusion and exclusion criteria. Obtaining a verbal numerical rating of pain severity is standard in this setting.

If the patient is eligible and the Cat 2 doctor or CIC believe that the time involved in patient recruitment will not have an adverse effect on either that patient’s management or the concurrent work of the ED, then either of these doctors or another delegate may broach study participation with the patient and their parent/guardian.

Initially, verbal consent for the administration of ketamine as a pain reliever will be sought from the parent/guardian by reading a pre-prepared information sheet describing the study. This will be done to prevent delays to analgesia and the increased distress that are likely to occur in the recruitment of study subjects when a complete written PICF must be read and completed by the patient’s parent/guardian prior to the administration of analgesia. A similar approach to consent has been approved for a parallel adult dose-finding study by Southern Health HREC-A

Written consent will then be obtained once the printed PICF is given to the parent/guardian after analgesia has been ordered and administered, for the data collection, analysis and storage of pain scores, adverse events and other clinical data.

When the patient parent/guardian’s initial verbal consent is obtained, the attending doctor will calculate the appropriate dosage of Ketamine from the chart attached to the data collection form and chart this for administration via the intranasal route.

The drug will be prepared by the attending nurse(s) who will also refer to the Study Ketamine Dosing Table
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable - cohort treatment study
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
24/02/2012
Actual
1/02/2012
Date of last participant enrolment
Anticipated
30/06/2012
Actual
30/06/2012
Date of last data collection
Anticipated
Actual
Sample size
Target
60
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 284408 0
Hospital
Name [1] 284408 0
Department of Emergency Medicine, Monash Medical Centre, Clayton
Country [1] 284408 0
Australia
Primary sponsor type
Hospital
Name
Southern Health
Address
Clayton Rd,
Clayton, Vic, 3168
Country
Australia
Secondary sponsor category [1] 283338 0
None
Name [1] 283338 0
Address [1] 283338 0
Country [1] 283338 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 286363 0
Southern Health Humans Research and Ethics Committee
Ethics committee address [1] 286363 0
Ethics committee country [1] 286363 0
Australia
Date submitted for ethics approval [1] 286363 0
08/12/2011
Approval date [1] 286363 0
01/01/2012
Ethics approval number [1] 286363 0
11370B

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 33554 0
Prof Andis Graudins
Address 33554 0
Dept of Emergency Medicine
135 Dandenong Hospital,
David Street,
Dandenong, Victoria, 3175
Country 33554 0
Australia
Phone 33554 0
+61 3 9554 9340
Fax 33554 0
Email 33554 0
[email protected]
Contact person for public queries
Name 16801 0
Professor Andis Graudins
Address 16801 0
Dept of Emergency Medicine
135 Dandenong Hospital,
David Street,
Dandenong, Victoria, 3175
Country 16801 0
Australia
Phone 16801 0
+61395943193
Fax 16801 0
Email 16801 0
[email protected]
Contact person for scientific queries
Name 7729 0
Professor Andis Graudins
Address 7729 0
Dept of Emergency Medicine
135 Dandenong Hospital,
David Street,
Dandenong, Victoria, 3175
Country 7729 0
Australia
Phone 7729 0
+61395943193
Fax 7729 0
Email 7729 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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No documents have been uploaded by study researchers.

Documents added automatically
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