Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000064808
Ethics application status
Approved
Date submitted
25/11/2020
Date registered
27/01/2021
Date last updated
27/01/2021
Date data sharing statement initially provided
27/01/2021
Date results information initially provided
27/01/2021
Type of registration
Retrospectively registered

Titles & IDs
Public title
A randomised controlled trial of ice to reduce the pain of immunisation - the ICE trial
Scientific title
A randomised controlled trial of ice to reduce the pain of immunisation in adults receiving the influenza vaccination - the ICE trial
Secondary ID [1] 302873 0
Nil known
Universal Trial Number (UTN)
U1111-1261-8066
Trial acronym
the ICE trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Injection-related pain 319868 0
Condition category
Condition code
Anaesthesiology 317806 317806 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This double-blinded, multicentre, prospective randomised controlled trial is designed to investigate impact of ice packs in reducing injection-related pain in medical students receiving influenza vaccines at JCU health in Townsville and Mackay City Medical. The study will include 90 patients who receive influenza vaccines. An ice pack (0 degrees C) will be applied to the site of injection for 30 seconds in participants randomised to the intervention group (n = 45) immediately prior to vaccination.
General practitioners at participating practices will be responsible for administering vaccines and ice packs/ cold-packs. Members of the research team will be present during vaccination clinics to monitor adherence to the intervention.
Intervention code [1] 319159 0
Treatment: Other
Comparator / control treatment
A placebo cold pack (10°C) will be applied to those in the control group (n = 45) for the same duration immediately prior to vaccination.
A vaccination protocol will standardise the management across both study arms. This will be formulated following discussion with participating doctors and nurses. We will use the Royal Australian College of General Practitioners (RACGP) vaccination guidelines. As per this protocol, skin vaccination will be undertaken in a consistent manner for both study arms and will be the same across all sites. The post-immunisation processes will be identical, with all patients receiving a standard set of verbal and written post-immunisation instructions.
Control group
Placebo

Outcomes
Primary outcome [1] 325831 0
The primary outcome measure is the incidence of pain using a Visual Analogue Score (VAS), immediately post immunisation. Based on previous research, estimates of the minimum clinically significant difference in VAS score range from 13 mm to 17 mm, and thus a midpoint of 15 mm is chosen. To measure primary outcome data, participants in both study arms will be given a pre-printed VAS. Patients are to record their immediate post-immunisation pain along the VAS and return the form to a collection box placed outside the doctor’s room.
Timepoint [1] 325831 0
Immediately after vaccination
Secondary outcome [1] 389262 0
Secondary outcome measures will include adverse reactions to the vaccination, manifesting as any one of:

- Anaphylaxis
o Throat, lips, face or tongue swelling
o Difficulty breathing
o Chest tightness
o Hives

- Skin irritation or contact dermatitis
o Blisters
o Severe pain
o Erythema
o Pruritus
o Bruising
o Redness

We understand that it is not typical for patients to present for follow-up after flu vaccination. As such, the patients will be asked to assess the injection site 24 hours after following vaccination, complete a self-assessment form and return it to the vaccination clinic within 48 hours. Additionally, the vaccination sites will be assessed for evidence of side effects if they present opportunistically or for review due to side effects. All immunisation reactions will be photographed to ensure a thorough assessment of each injection site reaction. All immunisation reactions will be treated according to standard treatment guidelines.
Timepoint [1] 389262 0
24 hours post-vaccination

Eligibility
Key inclusion criteria
- All patients over the age of 18 undergoing flu vaccination at participating vaccination clinics during the study period who:
o Have the capacity to give informed consent and;
o Are able to return for assessment of the vaccination reaction

- Patients who do not have a history of reaction to ice
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
· Allergy to ice (cold anaphylaxis)

· History of serious immunisation reactions

· Allergy to flu vaccination

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation concealment will be attained by using sealed, numbered, tamperproof opaque envelopes such than neither the patient, nor the clinicians involved in their care, will be aware of their allocation until after they have consented to be a part of the trial.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be performed at the level of the patient with an allocation ratio of 1:1. A computer-generated random number table (https://www.sealedenvelope.com/simple-randomiser/v1/lists) will be used
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Primarily, an intention to treat analysis of all patients included in randomisation will be undertaken. Each individual person will be considered as the unit of analysis. Our p-values will be two tailed and p < 0.05 will be considered statistically significant. Baseline data across icepack and cold-pack groups will be assessed for marked differences. The measurement of pain (the primary dependent variable) in each of the two groups of the trial will then be compared using an independent t-test or a Mann-Whitney U test. Multivariable logistic regression analysis will be applied if case differences exist between intervention and control groups at baseline and the analysis requires adjustment for confounders. Sensitivity

testing will be conducted for any participants lost to follow-up. Per protocol analysis will evaluate potential effects of systematic biases due to non-compliers.

Recruitment
Recruitment status
Stopped early
Data analysis
Data analysis is complete
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
It is important to acknowledge the impact the COVID-19 pandemic had on our study. Compliance with government regulations was required to ensure the safety of patients, health professionals and research staff. Some members of our research team and participating GP practices were deployed in other areas, with different sets of responsibilities. Due to travel restrictions, we were unable to travel to conduct an arm of the study in Townsville and we recruited from a single centre in Mackay, thereby decreasing our sample size. Government restrictions permitted only 10 people inside the participating general practice at one time and several rooms were used to ensure adequate social distancing. To comply with government guidelines for quarantine, students were advised not to attend the clinic if they were symptomatic or had recently travelled to high risk areas.

The main limitations of this study was the exclusion of a study site due to covid-19 restrictions Our final sample size decreased from 90 to 35 participants, which reduced the ability to analyse findings.
Date of first participant enrolment
Anticipated
Actual
28/03/2020
Date of last participant enrolment
Anticipated
Actual
28/03/2020
Date of last data collection
Anticipated
Actual
31/03/2020
Sample size
Target
90
Accrual to date
Final
35
Recruitment in Australia
Recruitment state(s)
QLD

Funding & Sponsors
Funding source category [1] 307289 0
University
Name [1] 307289 0
James Cook University
Country [1] 307289 0
Australia
Primary sponsor type
University
Name
James Cook University
Address
Building K, MacKay Base Hospital, 439 Bridge Rd, West Mackay QLD 4740
Country
Australia
Secondary sponsor category [1] 307928 0
None
Name [1] 307928 0
Address [1] 307928 0
Country [1] 307928 0
Australia
Secondary sponsor category [2] 307929 0
None
Name [2] 307929 0
Address [2] 307929 0
Country [2] 307929 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307387 0
James Cook University Human Research Ethics Committee
Ethics committee address [1] 307387 0
1 James Cook Dr, Douglas QLD 4811
Ethics committee country [1] 307387 0
Australia
Date submitted for ethics approval [1] 307387 0
06/04/2019
Approval date [1] 307387 0
29/10/2019
Ethics approval number [1] 307387 0
H7871

Summary
Brief summary
Introduction: Pain is an adverse effect associated with vaccination. Ice may be used to reduce pain. This prospective randomised controlled trial aims to investigate the effect of applying an ice pack prior to immunisation on the outcome of pain in medical students receiving their flu vaccines.

Methods and analysis: This double-blinded, multicentre, prospective randomised controlled trial is designed to investigate impact of ice packs in reducing injection-related pain in medical students receiving influenza vaccines. The study will include 90 patients who receive influenza vaccines. An ice pack (0°C) will be applied to the site of injection for 30 seconds in participants randomised to the intervention group (n = 45). A placebo cold pack (10°C) will be applied to those in the control group (n = 45) for the same duration immediately prior to vaccination. A standardised vaccination protocol will be used across both study arms. The primary objective is to test the hypothesis that applying an ice pack will significantly reduce pain in comparison to a cold pack. Secondary objectives aim to assess any potential adverse reactions. The study commenced in January 2019 and is due for completion by December 2020. The main analysis of data will follow the intention to treat principle. The measurement of pain, the primary dependent variable, in each of the two groups will be compared using an independent t-test or a Mann-Whitney U test. Multivariable logistic regression analysis will be used if necessary.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 107054 0
Miss Yashodha Ediriweera
Address 107054 0
James Cook University, Building K, MacKay Base Hospital, 439 Bridge Rd, West Mackay QLD 4740
Country 107054 0
Australia
Phone 107054 0
+61 0456246115
Fax 107054 0
Email 107054 0
yashodha.ediriweera@my.jcu.edu.au
Contact person for public queries
Name 107055 0
Miss Yashodha Ediriweera
Address 107055 0
James Cook University, Building K, MacKay Base Hospital, 439 Bridge Rd, West Mackay QLD 4740
Country 107055 0
Australia
Phone 107055 0
+61 0456246115
Fax 107055 0
Email 107055 0
yashodha.ediriweera@my.jcu.edu.au
Contact person for scientific queries
Name 107056 0
Miss Yashodha Ediriweera
Address 107056 0
James Cook University, Building K, MacKay Base Hospital, 439 Bridge Rd, West Mackay QLD 4740
Country 107056 0
Australia
Phone 107056 0
+61 0456246115
Fax 107056 0
Email 107056 0
yashodha.ediriweera@my.jcu.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
For patient confidentiality reasons


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseA randomised controlled trial of ice to reduce the pain of immunisation-the ice trial.2021https://dx.doi.org/10.3390/TROPICALMED6030158
N.B. These documents automatically identified may not have been verified by the study sponsor.