The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12617000707369
Ethics application status
Approved
Date submitted
5/04/2017
Date registered
17/05/2017
Date last updated
19/05/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
Prospective randomised controlled study of pharyngo-oesophageal dilatation in Head and Neck cancer therapy-induced dysphagia: Evaluation of efficacy and safety
Scientific title
Prospective randomised controlled study of pharyngo-oesophageal dilatation in Head and Neck cancer therapy-induced dysphagia: Evaluation of efficacy and safety
Secondary ID [1] 291620 0
NHMRC APP1046882
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
dysphagia 302745 0
head and neck cancer 302746 0
Condition category
Condition code
Oral and Gastrointestinal 302262 302262 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Cancer 302394 302394 0 0
Head and neck

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Recruited participants are randomised into 2 groups: 1) treatment arm; 2) placebo arm.

All participants will undergo a diagnostic endoscopic examination (standard of practice) using a gastroscope with an outer diameter of 9.2mm (Olympus GIF-H190, Olympus Corp, Tokyo), at Day Surgery St Goerge Hospital. Sedation is administered by anaesthesiologists using fentanyl, midazolam, and propofol.

Participants allocated to the treatment arm will receive a series of endoscopic dilatations at of the pharyngo-oesophageal junction at the time endoscopy. Endoscopic dilatations are performed using bougie dilators (Savary-Gilliard, Wilson-Cook Medical, Winston-Salem, NC, USA). The selection of initial dilator size is based on an estimated lumen diameter from endoscopic view as determined by experienced gastroenterologist consultants. Dilators are passed sequentially in increments of 1mm diameter with periodic inspection following some or all dilator passages until one or more of the following is reached: 1) mucosal tear identified upon re-inspection, or 2) a maximal dilator diameter of 16mm is passed. Based on our pilot data [Paramsohthy, S et al. Gastroenterology 2012 suppl), a median of 3 dilatations per patient was necessary to achieve an adequate clinical response. Hence, patients are re-scheduled for repeat dilatation at 2 weekly intervals until 1) satisfactory clinical response is achieved on global assessment; or 2) a maximal dilator of 16mm is passed; or 3) further increment in dilator size is considered unsafe.

Participants allocated to placebo arm will receive no endoscopic dilatation.
Intervention code [1] 297696 0
Treatment: Surgery
Comparator / control treatment
Participants who are randomised into the placebo arm will undergo one session of endoscopic examination with no dilatation of the pharyngo-oesophageal junction.
Control group
Placebo

Outcomes
Primary outcome [1] 301674 0
Short-term clinical response 3-months after the endoscopic dilatation, defined as 1) a decrease in Sydney Swallow Questionnaire score by 200 or more; and 2) satisfactory response based on the global assessment.
Timepoint [1] 301674 0
3-months after treatment
Secondary outcome [1] 333532 0
Relapse of dysphagia, defined as 1) an increase in Sydney Swallow Questionnaire score to within 20% of pre-dilatation baseline; and 2) clinical need for intervention.
Timepoint [1] 333532 0
Follow-up up to 24 months post-dilatation.

Eligibility
Key inclusion criteria
1) self-reported problematic pharyngeal dysphagia 12 months beyond the surgeries and chemoradiation for head and neck cancer; 2) abnormal Sydney Swallow Questionnaire score (above 234).
Minimum age
50 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) local cancer recurrence; 2) any neurological disorders known to cause pharyngeal dysfunction (e.g. Parkinson's disease, cerebral vascular accident, inflammatory myopathy, motor neuron disease).

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)
Central randomisation by computer will generate allocation sequence for recruited participants. Allocation envelopes are sealed in opaque envelopes that are kept off-site. Concealed envelopes are provided to the proceduralists, and are opened once the participants are under sedation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation involving 2 strata:
1) Head and Neck Cancer treatment history: Chemoradiation only vs. Total Laryngectomy.
2) Dysphagia treatment history: Previous Dilatation vs. No Previous Dilatation.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving 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)
Efficacy
Statistical methods / analysis
Sample size calculation: The therapeutic response rate of endoscopic dilatation in the target popultion in existing case series ranged between 67% to 75%. Accepting 65% response rate and 20% placebo response, a total sample size of 44 (22 patients per treatment arm) was estimated (a 0.05 and power 0.8, Fisher’s exact test).

Statistical analysis: Categorical baseline variables were compared using chi-square tests. Continuous baseline variables are presented as means with 95% confidence intervals, and were compared using unpaired Student’s t-test. Intention to treat analysis will be used to compare the clinical response rate between the two treatment groups, using Chi-squares test. Paired Student’s t-test will be used to compare the within-subject changes in Sydney Swallow Questionnaire score. Chi-squares test was used for subgroup and risk factor analysis. Kaplan-Meier analysis was used to determine dysphagia relapse rate. Cox regression was used to determine risk factors for relapse of dysphagia.

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)
NSW
Recruitment hospital [1] 8053 0
St George Hospital - Kogarah
Recruitment postcode(s) [1] 15706 0
2217 - Kogarah

Funding & Sponsors
Funding source category [1] 296112 0
Government body
Name [1] 296112 0
NHMRC
Address [1] 296112 0
16 Marcus Clarke Street, Canberra City, ACT 2600
Country [1] 296112 0
Australia
Primary sponsor type
University
Name
St George & Sutherland Clinical School, University of New South Wales
Address
Clinical Sciences (WRPitney) Building, Short Street, St George Hospital, Kogarah NSW 2217
Country
Australia
Secondary sponsor category [1] 295008 0
None
Name [1] 295008 0
Address [1] 295008 0
Country [1] 295008 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297366 0
St Vincent's Hospital Human Research Ethics Committee
Ethics committee address [1] 297366 0
Research Office, Level 6 deLacy Building, St Vincent's Hospital, 390 Victoria Street
Darlinghurst NSW 2010
Ethics committee country [1] 297366 0
Australia
Date submitted for ethics approval [1] 297366 0
09/06/2010
Approval date [1] 297366 0
21/03/2011
Ethics approval number [1] 297366 0
10/197

Summary
Brief summary
The primary purpose of this trial is to evaluate the efficacy of pharyngo-oesophageal dilatation for improving ease and comfort of swallowing in patients with head and neck cancer therapy-induced swallowing difficulty.

Who is it for?
You may be eligible to enroll in this trial if you are aged 18 or over and have been diagnosed with head and neck cancer for which surgery and chemoradiation therapy finished at least 12 months previously, which has caused ongoing difficulty swallowing.

Study details
All participants enrolled in this trial will be randomly allocated (by chance) to receive either the dilatation procedures, or to receive a single oeosophageal endoscopy during which no dilatation is provided. Participants in the dilatation group will receive a series of dilatation procedures. These involve passage of dilators to expand the calibre of the oesophagus under sedation and will occur at 2-3 weekly intervals. All participants will be followed up for 2 years following the final procedure to evaluate swallowing symptoms and satisfaction with the treatment.

It is hoped that this trial will provide information on whether pharyngo-oesophageal dilatation may be an effective method for reducing symptoms of difficulties swallowing which have been caused by cancer therapies for head and neck cancer patients.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 73826 0
Prof Ian Cook
Address 73826 0
Department of Gastroenterology and Hepatology, St George Hospital, Gray St, Kogarah, NSW 2217
Country 73826 0
Australia
Phone 73826 0
+61 2 91132817
Fax 73826 0
+61 2 91133993
Email 73826 0
I.Cook@unsw.edu.au
Contact person for public queries
Name 73827 0
Dr Peter Wu
Address 73827 0
Department of Gastroenterology and Hepatology, St George Hospital, Gray St, Kogarah, NSW 2217
Country 73827 0
Australia
Phone 73827 0
+61 2 91132817
Fax 73827 0
+61 2 91133993
Email 73827 0
peteriungchiang.wu@health.nsw.gov.au
Contact person for scientific queries
Name 73828 0
Dr Peter Wu
Address 73828 0
Department of Gastroenterology and Hepatology, St George Hospital, Gray St, Kogarah, NSW 2217
Country 73828 0
Australia
Phone 73828 0
+61 2 91132817
Fax 73828 0
+61 2 91133993
Email 73828 0
peteriungchiang.wu@health.nsw.gov.au

No data has been provided for results reporting
Summary results
Not applicable