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Trial registered on ANZCTR


Registration number
ACTRN12619001474145
Ethics application status
Approved
Date submitted
9/09/2019
Date registered
24/10/2019
Date last updated
3/05/2021
Date data sharing statement initially provided
24/10/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Are probiotics useful post-tonsillectomy? – A randomised controlled study (feasibility trial)
Scientific title
Efficacy of probiotic gargles in reducing post-operative complications in adult post-tonsillectomy patients: A pilot double-blinded, randomised controlled trial (feasibility trial)
Secondary ID [1] 297122 0
None
Universal Trial Number (UTN)
U1111-1226-9224
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pain post tonsillectomy 311140 0
Secondary post tonsillectomy haemorrhage 312057 0
Condition category
Condition code
Surgery 309771 309771 0 0
Other surgery
Anaesthesiology 312787 312787 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intervention group – Probiotic (Streptococcus salivarius K12, BLIS) gargles: 2 scoop (Concentration will be 125 million CFU/scoop) dissolved in 20ml of warm water, gargle for 30 seconds and then swallow, four times a day for 14 days
*1 Scoop equivalent to ¼ teaspoon

Participant diaries and bottle returns will be used to monitor adherence to the intervention

Participants will use the probiotic 24hrs after surgery
Intervention code [1] 313387 0
Treatment: Drugs
Comparator / control treatment
Control – Placebo (isomalt) gargles: 2 scoop dissolved in 20ml of warm water, gargle for 30 seconds and then swallow, four times a day for 14 days

*1 Scoop equivalent to ¼ teaspoon

The placebo isolmalt is identical in appearance to the probiotic
Control group
Placebo

Outcomes
Primary outcome [1] 319250 0
Daily pain score determined by participant diary specifically designed for this study (Daily 14-day questionnaire)

Electronic questionnaire (specifically designed for this study) sent to patients via email or phone 14 days post surgery; Hard copy questionnaire (specifically designed for this study) if participants do not have access to email/mobile phone.


Timepoint [1] 319250 0
14 days post surgery. Outpatient clinic follow up on days 5, 14 and 28.
Primary outcome [2] 321409 0
Daily Requirement of endone as determined by participant diary specifically designed for study
Electronic questionnaire (specifically designed for this study) sent to patients via email or phone.
Hard copy questionnaire (specifically designed for this study) if participants do not have access to email/mobile phone.
Timepoint [2] 321409 0
14 days post surgery
Outpatient clinic follow up on days 5, 14 and 28.
Primary outcome [3] 321410 0
No pain as determined by participant diary specifically designed for study
Electronic questionnaire (specifically designed for this study)sent to patients via email or phone 14 days post surgery
Hard copy questionnaire (specifically designed for this study) if participants do not have access to email/mobile phone. .
Timepoint [3] 321410 0
14 days post surgery
Outpatient clinic follow up on days 5, 14 and 28
Secondary outcome [1] 367449 0
Readmission rate due to dehydration or poor oral intake as measured by hospital records
Timepoint [1] 367449 0
We will look at the 28 days post tonsillectomy for each patient
Secondary outcome [2] 367450 0
Amount of side effects daily experienced e.g. nausea, vomiting, constipation, drowsiness, halitosis, abdominal pain etc measured using participant diary specifically designed for study
Outcome tool: Daily questionnaire (specifically designed for this study)
Timepoint [2] 367450 0
14 days post surgery
Outpatient clinic follow up on days 5, 14 and 28.
Secondary outcome [3] 374012 0
Rate of post-tonsillectomy haemorrhage as assessed by hospital records
Outcome tool: 4-point Haemorrhage scale
Timepoint [3] 374012 0
28 days post surgery
Secondary outcome [4] 374892 0
Feasible Design of study – ability and time required of study staff to co-ordinate recruitment
The is a composite secondary outcome.
Outcome measurements include: 1) Ability to contact participants (Y/N) 2) duration of initial phone call to participants 3) staff required for initial recruitment phone call
Timepoint [4] 374892 0
By completion of data collection
Secondary outcome [5] 374893 0
Feasible Design of study - screening and clinic tasks will be assessed by recording number of staff required


Timepoint [5] 374893 0
By completion of data collection
Secondary outcome [6] 374894 0
Feasible Design of study - time required to recruit patients
Timepoint [6] 374894 0
By completion of data collection
Secondary outcome [7] 374895 0
Feasible recruitment and screening process will be assessed by time and number of people screened to enrol participants
Timepoint [7] 374895 0
By completion of data collection
Secondary outcome [8] 374896 0
Feasible randomisation process will be determined by ability to achieve balance of characteristics in group
Timepoint [8] 374896 0
By completion of data collection
Secondary outcome [9] 374897 0
Feasible Design of study - time required to screen and time required in clinic review.
Timepoint [9] 374897 0
By completion of data collection
Secondary outcome [10] 375491 0
Adherence – adherence in both groups assessed by taking probiotic/placebo gargle as measured by participant diaries and bottle return, attending follow up appointments and completing daily questionnaires (specifically designed for this study). All and each are a composite secondary outcome
Timepoint [10] 375491 0
By completion of data collection
Secondary outcome [11] 375492 0
- Safety will be assessed by the number and description of both serious adverse events (any admission to the emergency department or hospitalisation, life threatening events or results in significant morbidity or death) and other adverse events by group. Serious adverse events (including haemorrhage requiring operative intervention, readmission to pain and dehydration or septicaemia) will be adjudicated by a Independent Medical Monitoring team (two independent Ear Nose and Throat specialists) as not related to study, probably not related, unlikely but possibly related or probably related to study

Hospital records and participant diaries will be used to assess this outcome
Timepoint [11] 375492 0
28 days post surgery
Secondary outcome [12] 375493 0
Retention will be assessed number of participants that withdrew by group
Timepoint [12] 375493 0
By completion of data collection

Eligibility
Key inclusion criteria
- Age 18-55
- Elective Tonsillectomy or adenotonsillectomy only
- Indication of operation (one of the following): asymmetric tonsillar enlargement, recurrent tonsillitis, previous quinsy (> one), sleep disordered breathing, halitosis, tonsillolith
- Weight must be more than 50kg.
Minimum age
18 Years
Maximum age
55 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Allergic to opioids / codeine / Endone™ / paracetamol
Lactose intolerance
Unstable metabolic diseases/disorder
Heart failure or a history of endocarditis
Immunocompromised
Kidney disease
Liver disease
Hemorrhagic diathesis
Other concomitant surgical procedures.
Pregnancy
Patients who are currently taking NSAIDs e.g.: Celebrex™, Aspirin, etc.
Patients who are on regular opiates or Paracetamol
Recent use of probiotics within 1 month

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)
The trial or placebo pack will be provided on sealed envelope to the participant by pharmacist and will be recorded on an password protected electronic database.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated randomisation (using Microsoft Excel™) is undertaken by the department of pharmacy.
A pharmacist who will not be involved in the analysis of the trial results will prepare the randomisation schedule using block randomisation to maintain balance between treatment arms.
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
Phase 3
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
As this trial is a feasibility pilot trial we have elected to choose a number of 30 patients (15 patients per group). This number was chosen as we are limited by number of patients currently on waiting list awaiting tonsillectomy or adenotonsillectomy. We have also elected this number to demonstrate as an ability to demonstrate safety and feasibility of the trial. Outcome measures such pain, use of analgesics, and rates of readmission will be calculated and a statistical analysis will be performed. We will use the results from this study to perform a more accurate power analysis in designing a larger clinical trial.

Recruitment
Recruitment status
Recruiting
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)
VIC
Recruitment hospital [1] 13269 0
Frankston Hospital - Frankston
Recruitment postcode(s) [1] 25834 0
3199 - Frankston

Funding & Sponsors
Funding source category [1] 301683 0
Hospital
Name [1] 301683 0
Peninsula Health
Address [1] 301683 0
Professor Srikanth Velandai
PO Box 52 Hastings Road, Frankston, VIC 3199
Country [1] 301683 0
Australia
Primary sponsor type
Hospital
Name
Frankston Hospital
Address
Peninsula Health
2 Hastings Road, Frankston, VIC 3199
Country
Australia
Secondary sponsor category [1] 303965 0
None
Name [1] 303965 0
Address [1] 303965 0
Country [1] 303965 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302403 0
Human Research Ethics and Governance - Peninsula Health
Ethics committee address [1] 302403 0
2 Hastings Road, Frankston VIC 3199
Ethics committee country [1] 302403 0
Australia
Date submitted for ethics approval [1] 302403 0
31/03/2019
Approval date [1] 302403 0
17/09/2019
Ethics approval number [1] 302403 0
HREC/51745/PH-2019

Summary
Brief summary
Tonsillectomy is the most commonly performed otolaryngologic procedure. Despite advances in surgical techniques, the morbidity post-tonsillectomy remains high especially in the adult population. Pain remains the most consistent and incapacitating symptom experienced by patients post-operatively. This includes the need for analgesics as well as the inability to resume normal diet and activity for several days. Severe pain has been reported in 20% to 50% of children and young adults who have undergone tonsillectomy. There have been many studies investigating a variety of factors that influence post-tonsillectomy pain in the aim of reducing post-operative morbidity and requirement of rescue analgesics such as opiates, which can also have devastating effects.
Hypothesis: For many years it has been suggested that post-tonsillectomy pain is further worsened by colonisation of tonsillar fossae with organisms that induce inflammatory response thereby making pain worse.
Intervention: We aim to determine if using a probiotic gargle (Streptococcus salivarius) for 14 days post surgery reduces pain and reduces usage of rescue analgesics such as endone. Streptococcus salivarius is already established in the human oral cavity a few hours after birth and remains there as a predominant commensal inhabitant. This product comes in powder or lozenge form and is recommended for daily use. We aim to use the probiotic in powder form as a gargle to maximise contact with affected area (i.e. tonsillar fossa). The comparison group will use a placebo gargle (isomalt). A daily post-tonsillectomy diary will be sent daily via email or mobile phone to patients to complete. Patients who do not have access to email or mobile phone will be provided with hard copy of the questionnaire. If probiotics can reduce post-operative complications in adult tonsillectomy patient patients we would reduce morbidity, reduce requirement for opiate analgesia, prevent overuse of antibiotics and reduce substantial costs to the healthcare system.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 90118 0
A/Prof David Hunter-Smith
Address 90118 0
Peninsula Health
2 Hastings Road, Frankston VIC 3199
Country 90118 0
Australia
Phone 90118 0
+61 0409787500
Fax 90118 0
Email 90118 0
dhuntersmith@mac.com
Contact person for public queries
Name 90119 0
Dr Michael Nasserallah
Address 90119 0
Peninsula Health
2 Hastings Road, Frankston VIC 3199
Country 90119 0
Australia
Phone 90119 0
+61 0434431296
Fax 90119 0
Email 90119 0
michael.nasserallah@gmail.com
Contact person for scientific queries
Name 90120 0
Dr Michael Nasserallah
Address 90120 0
Peninsula Health
2 Hastings Road, Frankston VIC 3199
Country 90120 0
Australia
Phone 90120 0
+61 0434431296
Fax 90120 0
Email 90120 0
michael.nasserallah@gmail.com

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?
Informed consent form
Ethical approval
How or where can supporting documents be obtained?
Type [1] 3781 0
Informed consent form
Citation [1] 3781 0
Link [1] 3781 0
Email [1] 3781 0
Other [1] 3781 0
Type [2] 5065 0
Ethical approval
Citation [2] 5065 0
Link [2] 5065 0
Email [2] 5065 0
Other [2] 5065 0
Summary results
No Results