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Trial registered on ANZCTR


Registration number
ACTRN12611001102965
Ethics application status
Approved
Date submitted
19/10/2011
Date registered
24/10/2011
Date last updated
13/03/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
A study of the effectiveness of intranasal ketamine in the treatment of moderate to severe pain in the emergency department
Scientific title
A study of the efficacy of intranasal ketamine in sub-dissociative doses for the treatment of moderate to severe pain in adult patients in the emergency department.
Secondary ID [1] 273257 0
Nil
Universal Trial Number (UTN)
U1111-1125-3296
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
acute pain 278998 0
Condition category
Condition code
Injuries and Accidents 279180 279180 0 0
Other injuries and accidents
Anaesthesiology 279182 279182 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A single dose of intranasal ketamine (0.7mg/kg) will be administered to adult patients presenting to the emergency department with a 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 interim 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 achieve significant fall in pain score ar 30 minutes and do not require rescue analgesia with parenteral opioids and do not show signs of sedation with the initial dosing regimen, this will be continued for the remaining numbers in the proposed cohort.

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 for the remaining 120 patients.

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 remaning 120 patients.
Intervention code [1] 269573 0
Treatment: Drugs
Comparator / control treatment
Nil
Control group
Uncontrolled

Outcomes
Primary outcome [1] 279819 0
Mean change in Visual Analog Scale pain score from pre-administration (T0) to 30 minutes post-administration (T30)
Timepoint [1] 279819 0
30 minutes post-administration of ketamine
Secondary outcome [1] 294505 0
a) Mean change in Visual Analog Scale pain score from pre-administration (T0) to 15 minutes (T15) and 60 minutes (T60) post-administration (T30).
Timepoint [1] 294505 0
15 and 60 minutes after ketamine administration
Secondary outcome [2] 294553 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] 294553 0
T 15, T30, T60 minutes
Secondary outcome [3] 294554 0
c) Percentage requiring an additional dose of ketamine
Timepoint [3] 294554 0
T15 minutes
Secondary outcome [4] 294555 0
d) Percentage responding to each description of satisfaction with amount of analgesia experienced (satisfied, not satisfied, uncertain)
Timepoint [4] 294555 0
T15, T30, T60.
Secondary outcome [5] 294556 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] 294556 0
at T15, T30, T60
Secondary outcome [6] 294557 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) will be recorded at.

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] 294557 0
T15, T30, T60

Eligibility
Key inclusion criteria
Age greater than or equal to 18 years of age

Self-report pain severity as being greater than or equal to 6 on the standard 11-point verbal rating scale (0 = none, 10 = worst pain imaginable)

Medical recommendation for parenteral analgesia (attending doctor’s discretion)

Pain from any cause other than the 3 specific exclusions (see below)
Minimum age
18 Years
Maximum age
100 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Known current pregnancy or patient suspects that might be pregnant at time of presentation or female of child-bearing age and not using any form of contraception.

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 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.

If patient consent is obtained, the attending doctor will calculate the appropriate dosage of Ketamine and chart this for administration via the intranasal route. The drug will be prepared by the attending nurse(s) who will 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
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 270065 0
Hospital
Name [1] 270065 0
Departments of Emergency Medicine, Southern Health
Address [1] 270065 0
Monash Medical Centre
Clayton Rd
Clayton, Vic, 3168
Country [1] 270065 0
Australia
Funding source category [2] 284083 0
Hospital
Name [2] 284083 0
Department of Emergency Medicine, Frankston Hospital
Address [2] 284083 0
Hastings Road,
FRANKSTON, Vic, 3199
Country [2] 284083 0
Australia
Primary sponsor type
Hospital
Name
Southern Health
Address
Clayton Rd,
Clayton, Vic, 3168
Country
Australia
Secondary sponsor category [1] 269028 0
None
Name [1] 269028 0
Address [1] 269028 0
Country [1] 269028 0
Other collaborator category [1] 252306 0
Hospital
Name [1] 252306 0
Peninsula Health
Address [1] 252306 0
Frankston Hospital
Hastings Road,
Frankston, Vic, 3199
Country [1] 252306 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 272022 0
Southern Health Humans Research and Ethics Committee
Ethics committee address [1] 272022 0
Monash Medical Centre
Clayton Rd
Clayton, Vic, 3168
Ethics committee country [1] 272022 0
Australia
Date submitted for ethics approval [1] 272022 0
17/10/2011
Approval date [1] 272022 0
04/01/2012
Ethics approval number [1] 272022 0
HREC/11/SHA/54
Southern Health HREC Ref: 11331A

Summary
Brief summary
This study aims ot assess the effectiveness of ketamine as an pain reliever when administered into the nasal passages in doses that do not produce sedation or anaesthesia in a group of adult emergency department patients coming to hospital with moderate to severe pain.
We hypothesise that ketamine will reduce pain effectively without significant sedation at the proposed dose.
A positive result may allow ketamine to be considered as an alternative pain reliever for acute pain in the emergency department that could be adminsitered through the nose and reduce the need for insertion of intravenous catheters in some patients suffering from moderate to severe pain.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 33285 0
Prof Andis Graudins
Address 33285 0
Dept of Emergency Medicine
135 Dandenong Hospital,
David Street,
Dandenong, Victoria, 3175
Country 33285 0
Australia
Phone 33285 0
+61 3 9554 9340
Fax 33285 0
Email 33285 0
andis.graudins@monash.edu
Contact person for public queries
Name 16532 0
Prof Professor Andis Graudins
Address 16532 0
Dept of Emergency Medicine
135 Dandenong Hospital,
David Street,
Dandenong, Victoria, 3175
Country 16532 0
Australia
Phone 16532 0
+61395943193
Fax 16532 0
Email 16532 0
andis.graudins@monash.edu
Contact person for scientific queries
Name 7460 0
Prof Professor Andis Graudins
Address 7460 0
Dept of Emergency Medicine
135 Dandenong Hospital,
David Street,
Dandenong, Victoria, 3175
Country 7460 0
Australia
Phone 7460 0
+61395943193
Fax 7460 0
Email 7460 0
andis.graudins@monash.edu

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary