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Trial registered on ANZCTR


Registration number
ACTRN12625000158460
Ethics application status
Approved
Date submitted
18/01/2025
Date registered
11/02/2025
Date last updated
11/02/2025
Date data sharing statement initially provided
11/02/2025
Type of registration
Retrospectively registered

Titles & IDs
Public title
A two-phase study investigating the quality of life benefit of additional 0.5% cocaine mouthwash to institutional standard of care mucositis management in head and neck cancer patients undergoing radiotherapy or chemoradiotherapy.
Scientific title
A two-phase study investigating the quality of life benefit of additional 0.5% cocaine mouthwash to institutional standard of care mucositis management in head and neck cancer patients undergoing radiotherapy or chemoradiotherapy.
Secondary ID [1] 313715 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
mucositis 336310 0
cancer 336311 0
Condition category
Condition code
Cancer 332845 332845 0 0
Head and neck

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention was the addition of 0.5% cocaine mouthwash (CMW) to institutional standard of care (SOC) management of mucositis-related pain in head and neck cancer patients undergoing radiotherapy or chemoradiotherapy.

This is a single centre, prospective sequential cohort study of eligible consecutive patients that was undertaken at a tertiary hospital in Perth, Western Australia (Sir Charles Gairdner Hospital) between 1 August 2016 and 11 November 2019.

Eligible patients had a histologically confirmed head and neck cancer receiving radiotherapy or chemoradiotherapy in the definitive or adjuvant setting. Patients were excluded if they were under 18 years of age, pregnant or breastfeeding, or allergic or intolerant to any of the study treatment intervention.

The study was conducted pragmatically and focused on the global impact of the intervention rather than individual patient benefit. The first cohort of patients (the CMW arm) received analgesia prescribed according to the analgesic ladder (see below) guidelines including CMW, and upon completion of the CMW arm, the SOC arm only received medications as per the analgesia guideline without the CMW.

The mucositis-related pain management guideline was established following consensus agreement between medical oncology, radiation oncology, palliative care and pain service teams and was disseminated after an educational session. Step 1 of the analgesic ladder focused on topical management. If the patient required topical therapy, all three of the following mouthwashes were provided – (1) benzydamine mouthwash, (2) lignocaine viscous 2% mouthwash, and (3) CMW (in the CMW arm only). Each mouthwash was encouraged to be used regularly four times a day and staggered in use to maximise relief. Step 2 of the analgesic ladder employed the use of short acting analgesia with preference for morphine elixir or hydromorphone elixir at standard doses on a when required basis. Step 3 focused on addition of long-acting analgesia with preference for long-acting oral morphine/ oxycodone or fentanyl patch. Step 2 and step 3 could be initiated simultaneously. The guidelines also recommended routine mouth care and oral hygiene. Patients were not blinded for the intervention. Patients were provided with analgesia prescription whilst undergoing radiotherapy or chemoradiotherapy and for up to 3 months after its completion as required. An a priori decision was not to mandate medication use diary from the patients given the already high burden of care and intervention in this patient group.

The decision to enrol patients sequentially in the two arms was pragmatic, based on the required minimum purchase and manufacturing of a batch of the CMW and with consideration of the expiry date of the drug. The SOC arm commenced when the CMW supplies were exhausted. That is, the SOC arm commenced on completion of the CMW arm.

Doses for medicines used in the analgesic ladder
Benzydamine 0.15% MW 15mL four times a day.
Lignocaine viscous 2% 10mL four times a day.
Cocaine MW 0.5% 15ml four times a day (in the intervention arm only)
Morphine elixir 1mg/mL 5mg hourly on a when required basis
Hydromorphone elixir 1mg/mL 1mg hourly on a when required basis
Long-acting analgesia (morphine, oxycodone or fentanyl) at standard doses prescribed in routine clinical practice
Intervention code [1] 330310 0
Treatment: Drugs
Comparator / control treatment
The SOC arm received analgesia as per the analgesic guidelines except the CMW.

Step 1 of the analgesic ladder focused on topical management. If the patient required topical therapy, the following mouthwashes were provided – (1) benzydamine mouthwash, and (2) lignocaine viscous 2% mouthwash. Both mouthwashes was encouraged to be used regularly four times a day and staggered in use to maximise relief. Step 2 of the analgesic ladder employed the use of short acting analgesia with preference for morphine elixir or hydromorphone elixir at standard doses on a when required basis. Step 3 focused on addition of long-acting analgesia with preference for long-acting oral morphine/ oxycodone or fentanyl patch. Step 2 and step 3 could be initiated simultaneously. The guidelines recommended routine mouth care and oral hygiene. Patients were not blinded for the intervention.
Control group
Active

Outcomes
Primary outcome [1] 340378 0
The primary objective and outcome was to assess the change in the quality of life from the addition of CMW to SOC management of mucositis-related pain in head and neck cancer patients undergoing radiotherapy or chemoradiotherapy.
Timepoint [1] 340378 0
At baseline, weekly during radiotherapy or chemoradiotherapy and at 1-month and 3-month following completion of the treatment.
Secondary outcome [1] 443905 0
Rate of analgesic prescription
Timepoint [1] 443905 0
Weekly during radiotherapy/chemoradiotherapy and at 1-month and 3-month following completion of the treatment.
Secondary outcome [2] 444309 0
Physician assessed mucositis grade
Timepoint [2] 444309 0
At baseline, weekly during radiotherapy/chemoradiotherapy and at 1-month and 3-month following completion of the treatment.
Secondary outcome [3] 444310 0
Patient reported pain
Timepoint [3] 444310 0
At baseline, weekly during radiotherapy/chemoradiotherapy and at 1-month and 3-month following completion of the treatment.
Secondary outcome [4] 444311 0
Number of hospital admissions during and up to 3-months post completion of radiotherapy or chemoradiotherapy
Timepoint [4] 444311 0
At least 3 months following completion of patient's treatment
Secondary outcome [5] 444312 0
Assessment of patient weight
Timepoint [5] 444312 0
At baseline, weekly during radiotherapy/chemoradiotherapy and at 1-month and 3-month following completion of the treatment.
Secondary outcome [6] 444313 0
Rate of enterostomy tube
Timepoint [6] 444313 0
At least 3 months following completion of patient's treatment

Eligibility
Key inclusion criteria
Eligible patients had a histologically confirmed mucosal head and neck cancer receiving radiotherapy or chemoradiotherapy in the definitive or adjuvant setting.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients were excluded if they were under 18 years of age, pregnant or breastfeeding, or allergic or intolerant to any of the study treatment intervention.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Single centre, prospective cohort study
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
The sample size was not formally calculated given the pragmatic conduct of the study. Based on the limited availability of the CMW, it was estimated that 30 – 50 patients would be recruited in each arm based on the total amount of CMW purchased for the conduct of the study and drug expiry date. A post-hoc analysis of the sample of size for the quality of life analyses demonstrated that a sample range of n=80 to 128 had 80% power to detect a range of effect size differences f=0.238 to 0.185 in a repeated measures mixed effects model between 2 groups over 10 timepoints with repeated measures correlations =0.5 (based on mean difference (standard deviation range) = 3.0 (6.3 to 8.1) points in the EORTC QLQ-C30 Global summary scale score) (G*Power 3.1.9.7).

Descriptive summaries of patient demographic and clinical data and secondary outcome data consist of frequency distributions for categorical data and means and standard deviations or medians, interquartile ranges and ranges for numerical (continuous, ordinal and count) data. Normality of distribution of continuous variables were assessed graphically and by Shapiro-Wilk tests.

Univariate treatment group comparisons were done using Chi squared or Fisher exact tests, as appropriate depending on cell counts, for categorical data comparisons and Mann-Whitney U tests for continuous data comparisons. Generalised linear mixed models (GLMM), with appropriate canonical links, and random patient effects, were used to obtain predicted mean estimates of EORTC QLQ-C30 and H&N35 scale scores. Tukey ladder of powers (ladder of transformations) graphical assessments was used to examine outcome distribution shapes. Model fit was checked by graphical assessment of the normality distribution of residuals. Results were summarised as estimated marginal means and 95% confidence intervals (CI), within group mean (95% CI) differences from baseline and between group cross-sectional adjusted mean (95% CI) differences were reported. Models were adjusted for age, gender, American Joint Committee on Cancer (AJCC) 7th Edition Staging, Charlson Comorbidity Index, 5% weight decrease from baseline, current smoking and enterostomy. GLMM utilise maximum likelihood estimation methods, allowing all available data points for all patients to be included in models regardless of missing data. Common Terminology Criteria for Adverse Events v4.03 Oral Mucositis Grading ordinal outcome was recoded into mucositis indicator (yes/no) and severity (nil-mild/moderate-severe) categories and modelled using mixed effects logistic regression, with results summarised using odds ratios and 95% CI. Models were adjusted for age, gender, AJCC 7th Edition Staging, Charlson Comorbidity Index, 5% weight decrease from baseline, current smoking and enterostomy status. Mean differences in QoL scores were considered clinically relevant if a minimum discrepancy of 10 points was observed [165]. All hypotheses were 2-sidedsided, and significance was set at alpha=0.05. Stata version 18.0 (StataCorp, College Station, TX) and IBM SPSS version 28.0 were used for data analysis.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
1/08/2016
Date of last participant enrolment
Anticipated
Actual
11/11/2019
Date of last data collection
Anticipated
Actual
5/08/2020
Sample size
Target
100
Accrual to date
Final
128
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 27491 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 43600 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 318181 0
Hospital
Name [1] 318181 0
Department of Radiation Oncology, Sir Charles Gairdner Hospital
Country [1] 318181 0
Australia
Primary sponsor type
Hospital
Name
Sir Charles Gairdner Hospital
Address
Country
Australia
Secondary sponsor category [1] 320566 0
None
Name [1] 320566 0
Address [1] 320566 0
Country [1] 320566 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316832 0
Sir Charles Gairdner and Osborne Park Health Care Group Human Research Ethics Committee
Ethics committee address [1] 316832 0
Ethics committee country [1] 316832 0
Australia
Date submitted for ethics approval [1] 316832 0
05/07/2016
Approval date [1] 316832 0
18/07/2016
Ethics approval number [1] 316832 0
12573

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

Contacts
Principal investigator
Name 139142 0
Dr Annette Lim
Address 139142 0
Peter MacCallum Cancer Centre; 305 Grattan St, Melbourne, VIC 3052
Country 139142 0
Australia
Phone 139142 0
+61 385595000
Fax 139142 0
Email 139142 0
Annette.Lim@petermac.org
Contact person for public queries
Name 139143 0
Annette Lim
Address 139143 0
Peter MacCallum Cancer Centre; 305 Grattan St, Melbourne, VIC 3052
Country 139143 0
Australia
Phone 139143 0
+61 385595000
Fax 139143 0
Email 139143 0
Annette.Lim@petermac.org
Contact person for scientific queries
Name 139144 0
Annette Lim
Address 139144 0
Peter MacCallum Cancer Centre; 305 Grattan St, Melbourne, VIC 3052
Country 139144 0
Australia
Phone 139144 0
+61 385595000
Fax 139144 0
Email 139144 0
Annette.Lim@petermac.org

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.