Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620001188921
Ethics application status
Approved
Date submitted
30/08/2020
Date registered
10/11/2020
Date last updated
9/08/2022
Date data sharing statement initially provided
10/11/2020
Date results information initially provided
9/08/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised trial of polaprezinc mouthwash for oral mucositis in cancer patients undergoing stem cell transplantation
Scientific title
A randomised trial on the effect of topical polaprezinc mouthwash on incidence and severity of oral mucositis in cancer patients undergoing haematopoietic stem cell transplantation
Secondary ID [1] 302107 0
Nil
Universal Trial Number (UTN)
Trial acronym
ToPaZ Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
oral mucositis 318733 0
Blood cancer 319370 0
Condition category
Condition code
Oral and Gastrointestinal 316748 316748 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Cancer 317336 317336 0 0
Hodgkin's
Cancer 317337 317337 0 0
Leukaemia - Acute leukaemia
Cancer 317338 317338 0 0
Leukaemia - Chronic leukaemia
Cancer 317339 317339 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 317340 317340 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 317341 317341 0 0
Myeloma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Polaprezinc mouthwash will be compared to sodium bicarbonate mouthwash (standard of care) in addition to saline mouthwash.
Treatment arm: Saline 10mL followed by polaprezinc 5mL four times a day as mouthwash
The concentration of polaprezinc mouthwash: 75mg in 20mL water. Each dose will be provided in a single use syringe.
The treatent duration: from hospital admission to neutrophil recovery (approximately 14-21 days)
Patient will swirl polaprezinc in the mouth for 30 seconds then spit. Used mouthwash syringes will be collected daily to assess adherence.
Intervention code [1] 318408 0
Prevention
Intervention code [2] 318409 0
Treatment: Drugs
Comparator / control treatment
Control treatment will be sodium bicarbonate mouthwash (standard of care) in addition to saline mouthwash.
Control arm: Saline 10mL followed by sodium bicarbonate 10mL four times a day as mouthwash
The treatment duration: from hospital admission to neutrophil recovery (approximately 14-21 days).
Saline and sodium bicarbonate will be provided as 500mL bottle and self administered by patients. Supply of the bottles will be recorded to assess adherence.
Control group
Active

Outcomes
Primary outcome [1] 324878 0
Incidence of grade 3 or 4 oral mucositis graded accordiing to WHO criteria
Oral mucositis assessment and WHO grading will be conducted daily by nurses, using the unit oral assessment sheet, as per unit standard procedure.
Timepoint [1] 324878 0
Anytime after hospital admission until neutrophil recovery. The outcome will be assessed every day.
Secondary outcome [1] 386068 0
Duration of WHO grade 3-4 oral mucositis
Oral mucositis will be graded daily using unit standard oral assessment sheet. Number of days with grade 3-4 will be calculated.
Timepoint [1] 386068 0
Anytime after hospital admission until neutrophil recovery. The outcome will be assessed every day.
Secondary outcome [2] 386070 0
Incidence of WHO grade 2-4 oral mucositis
Oral mucositis assessment and WHO grading will be conducted daily by nurses, using the unit oral assessment sheet, as per unit standard procedure.
Timepoint [2] 386070 0
Anytime after hospital admission until neutrophil recovery. The outcome will be assessed every day.
Secondary outcome [3] 386071 0
Duration of WHO grade 2-4 oral mucositis
Oral mucositis will be graded daily using unit standard oral assessment sheet. Number of days with grade 2-4 will be calculated.
Timepoint [3] 386071 0
Anytime after hospital admission until neutrophil recovery. The outcome will be assessed every day.
Secondary outcome [4] 386072 0
Incidence of taste disturbance
Patients will be asked by nurses if they have taste disturbance every day as per standard unit procedure.
Timepoint [4] 386072 0
Anytime after hospital admission until neutrophil recovery. The outcome will be assessed every day.
Secondary outcome [5] 386073 0
Patient reported oral soreness and swallowing difficulty due to the soreness. It is a composite secondary outcome. Patient reported outcome is assessed using oral mucositis daily questionnaire (OMDQ). Patients will be asked to fill the questionnaire every day from admission until neutrophil recovery
Timepoint [5] 386073 0
Anytime after hospital admission until neutrophil recovery. The outcome will be assessed every day.
Secondary outcome [6] 386074 0
The use of nutrition supplement. The use of enteral feeding or total parenteral nutrition will be collected from patient medical record
Timepoint [6] 386074 0
Anytime after hospital admission until neutrophil recovery.
Secondary outcome [7] 386075 0
Opioid usage will be collected from patient medical records. It will be converted to intravenous morphine equivalence.
Timepoint [7] 386075 0
Anytime after hospital admission until neutrophil recovery.
Secondary outcome [8] 386076 0
Adverse reaction (short term)
As this is a mouthwash and not ingested, adverse reaction is unlikely. When suspected or probable adverse reaction, it will be graded using CTCAE v5.0. The adverse reactions collected will be diarrhoea, constipation, nausea, vomiting, fever, rash, local irritation and other (to be specified).
Timepoint [8] 386076 0
Anytime during intervention is given, which is anytime after hospital admission until neutrophil recovery. The outcome will be assessed every day.
Secondary outcome [9] 387711 0
Duration of taste disturbance
Patients will be asked by nurses if they have taste disturbance every day as per standard unit procedure. Number of days with taste disturbance will be calculated
Timepoint [9] 387711 0
anytime from admission until neutrophil recovery
The outcome will be assessed every day.
Secondary outcome [10] 387712 0
Patient's acceptance for mouthwashes
Patient feedback will be collected using 11 point scale.
Timepoint [10] 387712 0
Data will be collected on the first day of mouthwash treatment, days 5 and 10 post transplantation.
Secondary outcome [11] 387714 0
Use of patient controlled analgesia (PCA). It will be collected from patient medical record.
Timepoint [11] 387714 0
Anytime from hospital admission until neutrophil recovery

Eligibility
Key inclusion criteria
Eligible patients are those who receive high dose chemotherapy with or without total body irradiation (TBI) followed by autologous or allogeneic HSCT. Patients receiving myeloablative regimens, fludarabine/melphalan, BEAM, high dose melphalan and other regimens with similar oral mucositis risks will be included.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients who have oral mucositis prior to HSCT
Patients with low risk of developing oral mucositis (e.g. CAR-T cells, Donor lymphocyte infusion)
Patients who are planned to be transfer or discharge from the hospital before neutrophil recovery.
Patients who require a translator

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)
Randomisation software (REDCap)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Stratified block randomisation using online software (Robust Randomisation App: https://clinicalresearch-apps.com/RRApp.html)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample size (54 each arm) was calculated based on the assumption that grade 3-4 OM will be reduced from 47% (control arm) to 20%, using 80% power and two-sided significance level of 5 %.
The effectiveness of the intervention will be evaluated by an intention-to-treat analysis of all patients who are randomised, irrespective of the duration of study drug administration. The primary outcome will be analysed using the chi square test or Fisher’s exact test. A p-value < 0.05 will be considered evidence of a significant difference in the primary outcome.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
31/01/2021
Actual
20/02/2021
Date of last participant enrolment
Anticipated
1/08/2022
Actual
1/07/2022
Date of last data collection
Anticipated
30/09/2022
Actual
8/08/2022
Sample size
Target
108
Accrual to date
Final
108
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 17307 0
Royal Brisbane & Womens Hospital - Herston
Recruitment postcode(s) [1] 31033 0
4029 - Herston

Funding & Sponsors
Funding source category [1] 306532 0
Charities/Societies/Foundations
Name [1] 306532 0
RBWH Foundation
Country [1] 306532 0
Australia
Primary sponsor type
Hospital
Name
Royal Brisbane and Women's Hospital
Address
Royal Brisbane and Women's Hospital,
Butterfield Street,
Herston, Qld 4006
Country
Australia
Secondary sponsor category [1] 307061 0
University
Name [1] 307061 0
The University of Queensland
Address [1] 307061 0
The University of Queensland,
Brisbane QLD 4072
Country [1] 307061 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306728 0
Royal Brisbane and Women’s Hospital HREC
Ethics committee address [1] 306728 0
Human Research Ethics Office
Lower ground floor, Executive Offices
James Mayne Building
Butterfield Street
HERSTON QLD 4029
Ethics committee country [1] 306728 0
Australia
Date submitted for ethics approval [1] 306728 0
31/08/2020
Approval date [1] 306728 0
04/11/2020
Ethics approval number [1] 306728 0
HREC/2020/QRBW/68154
Ethics committee name [2] 307083 0
University of Queensland HREC
Ethics committee address [2] 307083 0
Office of Research Ethics
The University of Queensland
Brisbane Qld 4072 Australia
Ethics committee country [2] 307083 0
Australia
Date submitted for ethics approval [2] 307083 0
06/11/2020
Approval date [2] 307083 0
Ethics approval number [2] 307083 0

Summary
Brief summary
This study will investigate the effect of topical polaprezinc mouthwash on the incidence of oral mucositis in cancer patients undergoing haematopoietic stem cell transplantation

Who is it for?
You may be eligible to join this study if you are aged 18 and above, have been diagnosed with blood cancer and will receive high dose chemotherapy with or without total body irradiation (TBI) followed by autologous or allogeneic haematopoietic stem cell transplantation

Study details
Participants in this study are randomly allocated (by chance) to one of two groups. Participants in one group will receive polaprezinc mouthwash 4 times daily from hospital admission until neutrophil recovery (approximately 20 days). Participants in the other group will receive sodium bicarbonate mouthwash 4 times daily from hospital admission until neutrophil recovery (approximately 20 days).

Daily oral assessment will be conducted by nurses and oral mucositis severity will be graded according to the WHO mucositis scale. Patients will be asked to complete an oral mucositis daily questionnaire that evaluates their oral pain and functional difficulties. Patients’ compliance, acceptability of the mouthwashes, total opioid and patient controlled analgesia (PCA) use, enteral nutrition (EN) and total parenteral nutrition (TPN) use will be collected.

If polaprezinc lower the incidence and severity of oral mucositis, it may be used in the future as an effective, inexpensive and safe prevention of oral mucositis.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 104814 0
Ms Midori Nakagaki
Address 104814 0
Cancer Care Pharmacy, Level 4 Joyce Tweddell Building,
Royal Brisbane and Women's Hospital,
Butterfield Street, Herston, Qld 4029
Country 104814 0
Australia
Phone 104814 0
+61 7 36470185
Fax 104814 0
Email 104814 0
[email protected]
Contact person for public queries
Name 104815 0
Ms Midori Nakagaki
Address 104815 0
Cancer Care Pharmacy, Level 4 Joyce Tweddell Building,
Royal Brisbane and Women's Hospital,
Butterfield Street, Herston, Qld 4029
Country 104815 0
Australia
Phone 104815 0
+61 7 36470185
Fax 104815 0
Email 104815 0
[email protected]
Contact person for scientific queries
Name 104816 0
Ms Midori Nakagaki
Address 104816 0
Cancer Care Pharmacy, Level 4 Joyce Tweddell Building,
Royal Brisbane and Women's Hospital,
Butterfield Street, Herston, Qld 4029
Country 104816 0
Australia
Phone 104816 0
+61 7 36470185
Fax 104816 0
Email 104816 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual participant data that underlie the results reported in this article, after deidentification
When will data be available (start and end dates)?
Beginning 6 months and ending 5 years following article publication
Available to whom?
Investigators whose proposed use of the data has been approved by the HREC approved this study
Available for what types of analyses?
For review of this study and meta-analysis
How or where can data be obtained?
Proposal should be directed to the RBWH HREC for approval. When approved, the principal investigator can be contacted by email ([email protected]) to obtain the data directly.


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.