Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616000889459
Ethics application status
Approved
Date submitted
30/06/2016
Date registered
6/07/2016
Date last updated
29/01/2019
Date data sharing statement initially provided
29/01/2019
Date results information initially provided
29/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Investigating Ketamine for treating the pain experienced by people bitten by a Red-Back Spider.
Scientific title
Investigating Ketamine for Red-Back Spider Envenoming (KuRED) - A Pilot Study
Secondary ID [1] 289581 0
None
Universal Trial Number (UTN)
U1111-1184-8476
Trial acronym
KuRED
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pain from a red-back spider bite 299325 0
Systemic effects of envenoming by a red-back spider 299327 0
Condition category
Condition code
Injuries and Accidents 299315 299315 0 0
Poisoning
Anaesthesiology 299373 299373 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A modified analgesia protocol will be followed prior to receiving the study intervention. The analgesia protocol will be as follows in all patients: paracetamol 1g orally PLUS oxycodone 10 mg orally. After this analgesia has been administered, the trial drug will be given to the patient. Patients with a history of a psychotic disorder, uncontrolled hypertension, ischaemic heart disease, tachyarrhythmia or pregnancy will not be included.

Patients will be given one dose of IV-infusion with ketamine 15 mg in 100 mL of normal saline over 15 minutes. The patient will be continuously monitored (ECG, pulse oximetry and non-invasive blood pressure), after which they will be admitted to the Emergency Department Observation Ward/Short Stay Unit. Study observations will also be performed at 30min, 1h, 2h, and 4h after the trial drug and immediately prior to discharge if kept in hospital for longer than this. Length of hospital stay is variable depending on the clinical condition of individual patients,

The first oral 50 mg ketamine lozenge will be given at 2 hours while the patient is in hospital and every 6 hours afterwards (4 lozenges in total). Therefore patients will be discharged on any of the remaining four ketamine lozenges. The patient will be given a sheet explaining when to take the lozenges and will be asked to record the times the treatment drug is taken as well as any other pain medication on a data sheet that will be collected by researchers. If the patient does not take all four doses of the trial medication, the remaining medication will also be returned to researchers. The patient will be contacted via phone by researchers at 24 and 48 hours.
Intervention code [1] 295183 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 298799 0
Clinically significant change in the severity of pain. Assessment of pain will be assessed using the verbal numerical rating score (VNRS), The treatement effect will be estimated as a mean reduction (and standard deviation) in the VNRS at 30min compared to baseline VNRS. In addition, a “clinically significant” change in the VNRS will be measured based on the Bird and Dickson for visual analogue scales. (see Bird SB, Dickson EW. Clinically significant changes in pain along the visual analog scale. Annals of emergency medicine. 2001;38(6):639-43) [ie. the change is dependent on the baseline starting point – 2 or greater for baseline score of 0 to 3, greater than 3 for baseline score of 4 to 6, and 5 or greater for baseline score of 7 to 10.
Timepoint [1] 298799 0
30 minutes after the commencement of the ketamine infusion
Secondary outcome [1] 325239 0
Adverse effects will be reported. Known side effects of ketamine include dissociative effects, dizziness, fatique, mood changes, hallucinations, nausea and head-ache. These will be assessed according to the side-effects rating scale for dissociative anaesthetics (SERSDA) questionnaire which asks the patient to rate a variety of symptoms as weak, modest, bothersome, or very bothersome.
Timepoint [1] 325239 0
30minutes, 1 hour, 2 hour, 4 hour and prior to discharge post infusion of ketamine
Secondary outcome [2] 325240 0
Administration of narcotic analgesics (oral or parenteral) in the emergency department after commencing the study drug. This will be recorded either on the supplied study data sheet or in patient notes by treating clinician.
Timepoint [2] 325240 0
At any time during admission
Secondary outcome [3] 325241 0
Clinically significant change in the verbal numerical rating score (VNRS). Assessment of pain will be assessed using the verbal numerical rating score (VNRS), The treatement effect will be estimated as a mean reduction (and standard deviation) in the VNRS at 30min compared to baseline VNRS. In addition, a “clinically significant” change in the VNRS will be measured based on the Bird and Dickson for visual analogue scales. [ie. the change is dependent on the baseline starting point – 2 or greater for baseline score of 0 to 3, greater than 3 for baseline score of 4 to 6, and 5 or greater for baseline score of 7 to 10.
Timepoint [3] 325241 0
24 hours after the ketamine infusion
Secondary outcome [4] 325242 0
Clinically significant change in the verbal numerical rating score (VNRS), Assessment of pain will be assessed using the verbal numerical rating score (VNRS), The treatement effect will be estimated as a mean reduction (and standard deviation) in the VNRS at 30min compared to baseline VNRS. In addition, a “clinically significant” change in the VNRS will be measured based on the Bird and Dickson for visual analogue scales. [ie. the change is dependent on the baseline starting point – 2 or greater for baseline score of 0 to 3, greater than 3 for baseline score of 4 to 6, and 5 or greater for baseline score of 7 to 10.
Timepoint [4] 325242 0
48 hours after ketamine infusion
Secondary outcome [5] 325243 0
Use of analgesics after discharge. The patient will be asked to complete a post-discharge data sheet which asks them to record any use of analgesics. They will also be asked about use of other analgesics in the follow up phone call at 24 and 48 hours.
Timepoint [5] 325243 0
Any time after discharge up to 48 hours after discharge.
Secondary outcome [6] 325244 0
Re-presentation for medical care (ED or GP). This is self-reported by patient on discharge data-sheet and also queried in follow up phone calls at 24 and 48 hours.
Timepoint [6] 325244 0
Any time after discharge up to 48 hours after discharge.

Eligibility
Key inclusion criteria
1. A definite or likely red-back spider bite according to either of the following criteria:
a. The spider causing the bite was clearly identified by the patient or clinician, OR
b. A clinical syndrome consistent with typical red-back spider envenoming that is: the sensation of a bite followed by two or more of:
*increasing pain over the first hour
*radiating, regional or generalised pain
*local or regional diaphoresis
AND
2. The patient has significant enough pain that the treating clinician would normally treat the pain with standard analgesia.
The syndrome of red-back spider envenoming used above is well defined and based upon a prospective study with formal identification of the responsible spiders.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients with pre-existing contraindications to study medication.
2. Children aged <18.
3. Presentation to hospital >36 hours after the bite.
4. Pregnancy or breastfeeding.

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)
N/A
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
N/A
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
Efficacy
Statistical methods / analysis
For this single-centred pilot study we will use the “rule of 12” for continuous variables. Increasing the sample size to 12 participants makes a profound difference in the width of confidence intervals for mean response, whereas increasing the sample size beyond 12 participants does not. At least 12 participants are recommended for pilot studies where the primary focus is estimating average values and variability for planning larger subsequent studies. This size is practical for most early-stage investigators to conduct within single centres while still providing valuable preliminary information. It will also be able to be completed in one red-back season at this site.

The treatment effect will be estimated as a mean reduction (and standard deviation) in the VNRS at 30min compared to baseline VNRS. In addition, a “clinically significant” change in the VNRS will be measured based on the Bird and Dickson for visual analogue scales. [ie. the change is dependent on the baseline starting point – 2 or greater for baseline score of 0 to 3, greater than 3 for baseline score of 4 to 6, and 5 or greater for baseline score of 7 to 10].

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/08/2016
Actual
9/01/2017
Date of last participant enrolment
Anticipated
30/04/2018
Actual
6/01/2018
Date of last data collection
Anticipated
2/05/2018
Actual
11/01/2018
Sample size
Target
12
Accrual to date
Final
10
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 6058 0
Calvary Mater Newcastle - Waratah

Funding & Sponsors
Funding source category [1] 293969 0
Government body
Name [1] 293969 0
National Health and Medical Research Council
Country [1] 293969 0
Australia
Primary sponsor type
University
Name
University of Newcastle
Address
University Drive, Callaghan
NSW 2308, Australia
Country
Australia
Secondary sponsor category [1] 292786 0
None
Name [1] 292786 0
none
Address [1] 292786 0
none
Country [1] 292786 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295384 0
Hunter New England Health Human Research Committee
Ethics committee address [1] 295384 0
Hunter New England Human Research Ethics Committee
Hunter New England Local Health District
Locked Bag 1
New Lambton NSW 2305
Ethics committee country [1] 295384 0
Australia
Date submitted for ethics approval [1] 295384 0
30/06/2016
Approval date [1] 295384 0
24/08/2016
Ethics approval number [1] 295384 0

Summary
Brief summary
AIMS
To investigate the effectiveness of ketamine for the treatment of pain associated with red-back spider envenoming
HYPOTHESES
Ketamine will result in a significant change in the level of pain experienced by patients envenomed by red -back spider.
RESEARCH DESIGN
This pilot study will test the effectiveness of subanesthetic, intravenous ketamine infusions for red-back spider envenoming in a small single centre pilot trial. All patients will also receive standard opioid and nonopioid analgesia. Patients will be over 18 years old
with moderate to severe red-back spider envenoming. The primary outcome will be clinically significant reduction in pain 30 minutes after administration of the ketamine infusion (compared to baseline). Informed written consent will be obtained from the patient using usual procedures prior to trial entry. All participants will receive analgesia according to a standardised protocol, commenced prior to administration of the trial drug. Patients will be cared for in an acute care area with physiological monitoring and if required intravenous parenteral analgesia as rescue medication.
STUDY INTERVENTION
A standard analgesia protocol will be followed prior to receiving the study intervention. The analgesia protocol will be as follows in all patients: paracetamol 1g orally PLUS oxycodone 10 mg orally. After the standard analgesia has been administered, the trial drug will be given to the patient. Subjects will be given an IV infusion with ketamine 15 mg in
100 mL of normal saline over 15 minutes. Clinical observations and patient pain score will be recorded at baseline and then post treatment at 30 minutes, one hour, two hours, four hours and on discharge.
OUTCOMES: The primary outcome will be a clinically significant reduction in the severity of pain 30 min after the commencement of the ketamine infusion using the VNRS
Trial website
Trial related presentations / publications
Ryan NM, James R, Downes MA, Isbister GK. Investigating Ketamine for Red-back Spider Envenoming. Presented at the Toxicology & Poisons Network Australasia (TAPNA) 2017 Scientific Meeting (Abstract poster presentation)..
Public notes
Attachments [1] 1810 1810 0 0
/AnzctrAttachments/371003-TAPNA 2017 KuRED NMR.pdf (Other)

Contacts
Principal investigator
Name 67070 0
Dr Nicole Ryan
Address 67070 0
Clinical Toxicology Research Group
University of Newcastle (Box 51)
Level 5, New Med Building
Calvary Mater Newcastle
Locked Bag 7
Hunter Region Mail Centre
NSW 2310
Country 67070 0
Australia
Phone 67070 0
+61 2 49211312
Fax 67070 0
+61 2 40143870
Email 67070 0
nicole.ryan@newcastle.edu.au
Contact person for public queries
Name 67071 0
Dr Nicole Ryan
Address 67071 0
Clinical Toxicology Research Group
University of Newcastle (Box 51)
Level 5, New Med Building
Calvary Mater Newcastle
Locked Bag 7
Hunter Region Mail Centre
NSW 2310
Country 67071 0
Australia
Phone 67071 0
+61 2 49211312
Fax 67071 0
+61 2 40143870
Email 67071 0
nicole.ryan@newcastle.edu.au
Contact person for scientific queries
Name 67072 0
Dr Nicole Ryan
Address 67072 0
Clinical Toxicology Research Group
University of Newcastle (Box 51)
Level 5, New Med Building
Calvary Mater Newcastle
Locked Bag 7
Hunter Region Mail Centre
NSW 2310
Country 67072 0
Australia
Phone 67072 0
+61 2 49211312
Fax 67072 0
+61 2 40143870
Email 67072 0
nicole.ryan@newcastle.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Pilot study.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
1197Study protocol   



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Plain language summaryNo Background: Redback spider envenoming causes sever... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseLow-dose ketamine provides poor analgesia for pain in redback spider envenoming.2019https://dx.doi.org/10.1111/bcp.14052
N.B. These documents automatically identified may not have been verified by the study sponsor.