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Trial registered on ANZCTR


Registration number
ACTRN12619001385134
Ethics application status
Approved
Date submitted
6/09/2019
Date registered
10/10/2019
Date last updated
29/11/2021
Date data sharing statement initially provided
10/10/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Does oral honey decrease the incidence of postoperative pain in children undergoing tonsillectomy procedures? (Bee - pain free)
Scientific title
A multi-centre, double-blinded, randomised controlled trial to investigate honey use to reduce pain in children post-tonsillectomy.
Secondary ID [1] 299186 0
NIL
Universal Trial Number (UTN)
NIL
Trial acronym
NIL
Linked study record
NIL

Health condition
Health condition(s) or problem(s) studied:
Pain following tonsillectomy surgery 314285 0
Condition category
Condition code
Anaesthesiology 312635 312635 0 0
Pain management
Oral and Gastrointestinal 313089 313089 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The standard treatment regime for discharge medication will be as per the institutional guidelines which are currently :
Parents are given written instructions and advised that pain control is best achieved with regular paracetamol and ibuprofen for at least 5-7 days and then as required. If the combination of paracetamol and ibuprofen within one hour is not effective then oxycodone can be given for extra pain relief.
Paracetamol: oral tablet/suspension, 15 mg/kg based on ideal body weight, patients advised to give regularly for at least 5 days every 4-6 hours.
Ibuprofen: oral tablet/suspension, 10 mg/kg. Parents advised to give regularly for at least the first five days, every 8 hours with no more than 3 doses in 24 hours.
Oxycodone: oral tablet/solution, 1 week prescription, 6 hourly, 0.05 mg/kg
Ondansetron: oral wafer 0.15 mg/kg

After informed written parental consent, paediatric patients, aged 1-16 years, undergoing tonsillectomy surgery will be randomised to receive either standard treatment alone or standard treatment plus a placebo or standard treatment plus one of two honeys to be taken on the ward before discharge and for at least 7 days post-discharge.

The honeys are:
Marri Honey
Western Australia Manuka Honey

The placebo is a sugar syrup and have the following ingredients:
Queen Glucose Syrup: Glucose syrup (derived from corn), sulphur dioxide.
It is gluten free, egg free, peanut free, soy free and vegan.
Pure Harvest Organic Rice Malt Syrup: organic brown rice
No additives or preservatives, gluten free, Vegan, GMO free, no artificial colours or flavours.
PharmAust Syrup BP: sucrose, water, methyl hydroxybenzoate

Each child in the honey / placebo groups will have a dosing regimen of 5 ml of honey or 5 ml of placebo regularly six times a day, if possible 30 minutes prior to eating. E.g. single dose will be given 30 minutes prior to a morning snack, an evening snack and mealtimes with the final dose being given before bedtime before brushing their teeth.

In hospital, parents will be instructed to give honey at the same times as for post-discharge i.e. before breakfast, morning snack, lunch, afternoon snack, dinner and at night. The duration of honey dosing in hospital on the day of surgery will therefore depend on the time of surgery.

Participants will be supplied with 1 kg of honey/placebo and instructed to take it on the day or surgery and continue for 7 more days. They may continue to take the honey/placebo for more than 7 days if a parent feels that their child is benefiting from it. Parents are instructed to dispose of the honey/placebo once they do not require it anymore.

Adherence to the intervention will be monitored by a participant diary and follow-up either by text message or phone by the research team
Intervention code [1] 315481 0
Treatment: Other
Comparator / control treatment
There are 4 arms in the study:
1-standard treatment alone (control arm)
2-standard treatment plus placebo (sugar syrup) (control arm)
3-standard treatment plus Marri Honey
4-standard treatment plus Western Australia Manuka Honey
Control group
Placebo

Outcomes
Primary outcome [1] 321288 0
The primary outcome measure will be self-reported pain using the Faces Pain Scale -revised (FPS-R) assessed 4 times daily for 7 days postoperatively. The pain intensity score for each discrete time point will be compared across groups at rest before breakfast and evening meals, and on swallowing during breakfast and evening meals
For children under 4 years of age, parents will be asked to rate their child's pain between 0 and 10 at rest and with swallowing.
Timepoint [1] 321288 0
Assessed 4 times daily for 7 days after the surgery. (primary endpoint Day 7)
Secondary outcome [1] 374604 0
Daily parents’ postoperative pain measure in the honey groups compared to placebo and control groups over study period.
Parents will be relate their "Parents' Postoperative Pain Measure" (PPPM) scores for each post-operative day which . This information will be collected from parents during followup (parents choice of either phone call or text on each day).
Timepoint [1] 374604 0
assessed daily for 7 days post-surgery.
Secondary outcome [2] 374605 0
Opioid analgesic intake-number of rescue doses received over 7 days between groups.
Assessed through parent reporting during follow-up.
Timepoint [2] 374605 0
7 days after surgery
Secondary outcome [3] 374606 0
Number of episodes of vomiting reported by parents between groups.Assessed through parent reporting during follow-up.
Timepoint [3] 374606 0
7 days after surgery
Secondary outcome [4] 374607 0
Number of unplanned representations to GP/Emergency Department in the seven days post-tonsillectomy between groups. This outcome is assessed from parent reporting.
Timepoint [4] 374607 0
7 days after surgery
Secondary outcome [5] 375387 0
Opioid analgesic intake, measured as oral morphine equivalents received over 7 days between groups.Assessed through parent reporting during follow-up.
Timepoint [5] 375387 0
7 days post tonsillectomy
Secondary outcome [6] 375388 0
Number of incidences of nausea reported by parents between groups.Assessed through parent reporting during follow-up.
Timepoint [6] 375388 0
7 days after surgery
Secondary outcome [7] 375389 0
The acceptability of honey by parents, global satisfaction score, Parent reported, collected during followup.
This will be measured by the numerical rating scale NRS-11 between 0 and 10.
Timepoint [7] 375389 0
7 days after surgery

Eligibility
Key inclusion criteria
Children and young adults aged 1 to 16 years undergoing elective tonsillectomy procedures under general anaesthesia.
Minimum age
1 Years
Maximum age
16 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Less than 1 year of age
Contraindication to honey, or placebo ingredients e.g. known allergy to honey or sugars, and children with diabetes

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation concealment by numbered containers of honey/placebo syrup.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
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
Intervention assignment
Parallel
Other design features
Multicentre trial.
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The data will be analysed as a longitudinal model. The analysis will indicate any differences in the four treatments (peroxide honey, non-peroxide honey, placebo and standard care only) and the change in pain score over time (days). More specifically, the model will include the effect of treatment, and measurement condition (at rest or swallowing), both over time, a random intercept for subject (to account for different baseline pain scores), a subject-specific random slope for treatment, and other study measurements detailed above (such as demographic variables Age, ASA, etc.).
Note that the longitudinal nature of the model will allow missing responses at a few time points. If substantial pain measurement data is missing then a decision will be made either to omit the record from analysis, or to impute the data using a standard technique (such as multiple imputation based on chained equations).
The simulations were repeated with several different parameter values (in particular a range of values for the mean vector around the mean specified above), and a sample size of 85 per group was found to be sufficient. Simulations give a power of 0.9 for a sample size of 85 per group. The power for a corresponding Anova with 85 patients and same standard deviation is only 70%. 15 patients are added per group due to loss in follow-up, cancellation of surgery, change of surgical plan and other protocol violations.
Regarding secondary outcomes, these will be assessed as follows.
1. Daily pain score as reported by parents (PPPM) will be analysed as a repeated measures model between groups, as for the children’s pain scores.
2. The amount of oxycodone administered to each group over the days will be analysed as a repeated measures model.
3. The total number of presentations for each group and episodes of vomiting post discharge will be analysed as a Poisson log-linear model or a contingency table using a chi square test of association
4. The acceptability of honey by parents, global satisfaction score will be analysed as a contingency table using a chi square test of association, or as a binomial log-linear model.
Demographics (age, weight, ASA, length of stay and operation data) will be included in the statistical modelling. Summary statistics will also be presented to enable and simplify direct group comparisons.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
4/11/2019
Actual
12/11/2019
Date of last participant enrolment
Anticipated
31/07/2021
Actual
21/07/2021
Date of last data collection
Anticipated
Actual
3/08/2021
Sample size
Target
400
Accrual to date
Final
400
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 14732 0
Perth Children's Hospital - Nedlands
Recruitment hospital [2] 14733 0
Subiaco Private Hospital - Subiaco
Recruitment hospital [3] 19448 0
St John of God Hospital, Subiaco - Subiaco
Recruitment hospital [4] 19449 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 27774 0
6009 - Nedlands
Recruitment postcode(s) [2] 27775 0
6008 - Subiaco
Recruitment postcode(s) [3] 34039 0
6008 - Subiaco
Recruitment postcode(s) [4] 34040 0
6150 - Murdoch

Funding & Sponsors
Funding source category [1] 303726 0
Charities/Societies/Foundations
Name [1] 303726 0
Perth Children's Hospital Foundation
Country [1] 303726 0
Australia
Funding source category [2] 303746 0
Other Collaborative groups
Name [2] 303746 0
Cooperative Research Centre for Honey Bee Products (CRCHBP)
Country [2] 303746 0
Australia
Funding source category [3] 310266 0
Government body
Name [3] 310266 0
Department of Health, Western Australia
Country [3] 310266 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Telethon Kids Institute
Address
Northern Entrance,
Perth Children's Hospital,
15 Hospital Ave,
Nedlands
WA 6009
Country
Australia
Secondary sponsor category [1] 303865 0
None
Name [1] 303865 0
Address [1] 303865 0
Country [1] 303865 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304251 0
Child and Adolescent Health Service Ethics Committee
Ethics committee address [1] 304251 0
Ethics committee country [1] 304251 0
Australia
Date submitted for ethics approval [1] 304251 0
20/05/2019
Approval date [1] 304251 0
19/09/2019
Ethics approval number [1] 304251 0
RGS0000003325

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

Contacts
Principal investigator
Name 96290 0
Prof Britta Regli-von Ungern-Sternberg
Address 96290 0
Perth Children's Hospital
15 Hospital Avenue
Nedlands
WA 6009
Country 96290 0
Australia
Phone 96290 0
+61420790101
Fax 96290 0
Email 96290 0
Britta.Regli-VonUngern@health.wa.gov.au
Contact person for public queries
Name 96291 0
Britta Regli-von Ungern-Sternberg
Address 96291 0
Perth Children's Hospital
15 Hospital Avenue
Nedlands
WA 6009
Country 96291 0
Australia
Phone 96291 0
+61420790101
Fax 96291 0
Email 96291 0
Britta.Regli-VonUngern@health.wa.gov.au
Contact person for scientific queries
Name 96292 0
Britta Regli-von Ungern-Sternberg
Address 96292 0
Perth Children's Hospital
15 Hospital Avenue
Nedlands
WA 6009
Country 96292 0
Australia
Phone 96292 0
+61420790101
Fax 96292 0
Email 96292 0
Britta.Regli-VonUngern@health.wa.gov.au

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


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
No additional documents have been identified.