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Trial registered on ANZCTR


Registration number
ACTRN12623000501640
Ethics application status
Approved
Date submitted
1/04/2023
Date registered
16/05/2023
Date last updated
28/04/2024
Date data sharing statement initially provided
16/05/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Endoscopic versus Surgical Treatment of Reflux
Scientific title
Quality of Life Following Endoscopic Anti-Reflux Mucosal Ablation versus Nissen Fundoplication for Refractory Reflux: a blinded randomised control trial
Secondary ID [1] 309346 0
None
Universal Trial Number (UTN)
U1111-1290-5421
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Reflux 329552 0
Condition category
Condition code
Surgery 326484 326484 0 0
Surgical techniques
Oral and Gastrointestinal 326749 326749 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
ARMA: (Anti-reflux mucosal ablation).

This will usually be performed under local sedation (where you will still be breathing on your own). Here the junction is lasered, which as it heals and scars, tightens the junction. This is called anti-reflux mucosal ablation (AMRA).

i.e. Ablation of gastro-oesophageal junction with argon plasma coagulation to create ulceration, fibrosis and subsequent constriction and tightening of the junction to prevent reflux.

Performed by Gastroenterologist. Procedure recorded on clinical record. Estimated time: 30 minutes.

Equipment:
APC (Argon plasma coagulation) generator & straight fire probe
EMR (endoscopic mucosal resection) solution – saline with 0.5% methylene blue
Clear endoscope cap
Specify endoscope with adequate flex (ie older scope)
IV (intravenous) omeprazole and antiemetic as part of sedation
ERBE Vio-200D Effect 3 100W (Mexican), VIO300D Effect 2 50W (Japanese)

Procedure
• Evaluate & clean GOJ (Gastro-oesophageal junction) & Hill Grade
• Mark borders of ablation; Effect 2 soft coagulation
o Markers around inner border 1cm from GOJ,
o Markers either side of 1cm greater curve untouched segment (<90o)
o Markers on outer border 1-2cm width, horse-shoe shape
• Lift cushion with EMR solution
• Sequential Ablation with ERBE
• Scrape/Clear tissue with cap
• Complete ablation if necessary
Intervention code [1] 325784 0
Treatment: Surgery
Comparator / control treatment
Laparoscopic Nissen Fundoplication

This is a keyhole (laparoscopic) operation under general anaesthetic (where you are completely asleep and unaware, with a machine breathing for you). This involves using tiny incisions (cuts) in the abdomen to view inside the body and perform the procedure, whereby the top of the stomach is gently wrapped around the lower oesophagus (gullet) to tighten the junction, which is currently too loose. This will help to prevent the acid to splash back which causes the reflux symptoms. This operation is called a Nissen Fundoplication.

Duration: 1-1.5 hours
Performed by General Surgical Consultants
Procedure will be recorded in clinical notes with a standard operation note.


Procedure
General anaesthetic
Antibiotic prophylaxis at induction
Patient placed in supine position
Optical entry in left upper quadrant of abdomen
Humidified CO2 insufflation to achieve pneumoperitoneum at pressure of 12mmHg
Including the optical entry port a total of 4 x laparoscopic working ports inserted across upper abdomen (2x5mm and 2x12mm) and laparoscopic liver retractor placed in epigastrium
Circumferential hiatal dissection performed using energy device to ensure >/=3cm intra-abdominal oesophageal length
Clear identification and preservation of anterior and posterior vagal nerves
Posterior +/- anterior crural closure calibrated loosely over 40f Bougie with non-absorbable 0 V-Loc™ (Covidien, Dublin, Ireland)
Mobilisation of fundus via proximal division of short gastric vessels for creation of a short (2-3cm) floppy 360 degree fundoplication. Wrap secured with 2.0 Ti-Cron sutures (Covidien, Mansfield, Mass).
Local anaesthetic applied intraperitoneal and to laparoscopic port sites
Pneumoperitoneum deflated
Monocryl subcuticular sutures to skin
Control group
Active

Outcomes
Primary outcome [1] 334326 0
The Gastroesophageal Reflux Disease-Health Related Quality of Life (GERD-HRQL) score
Timepoint [1] 334326 0
6 months post procedure
Primary outcome [2] 334327 0
24hr pH exposure (as assessed at pH testing) within normal range
Timepoint [2] 334327 0
Baseline (pre-procedure), then 6 months post-procedure.
Secondary outcome [1] 420250 0
GERD-HRQL quality of life outcome
Timepoint [1] 420250 0
Yearly for 3 years post procedure
Secondary outcome [2] 420252 0
SHORTFORM -36: Medical Outcomes Study Short-Form 36-Item Health Survey (SF-36)
Timepoint [2] 420252 0
6 months, then yearly for 3 years post procedure
Secondary outcome [3] 420253 0
QOL (quality of life) questionnaire for patients undergoing anti-reflux surgery (QOLARS)
Timepoint [3] 420253 0
6 months then yearly for 3 years post procedure
Secondary outcome [4] 420254 0
Operation time as noted from surgical records
Timepoint [4] 420254 0
Post-procedure
Secondary outcome [5] 421369 0
Blood loss as noted from surgical records
Timepoint [5] 421369 0
Post procedure
Secondary outcome [6] 421370 0
Hospital length of stay from medical records
Timepoint [6] 421370 0
At time of discharge
Secondary outcome [7] 421371 0
Pain as deduced from medical records
Timepoint [7] 421371 0
At time of discharge
Secondary outcome [8] 421372 0
Narcotic discontinuation / return to ADL (activities of daily living) - as advised by patient documented in medical record
Timepoint [8] 421372 0
Post-procedure and discharge from hospital
Secondary outcome [9] 421373 0
Complications: readmission, bleeding, or pain as noted from medical record
Timepoint [9] 421373 0
30 days post procedure
Secondary outcome [10] 421374 0
Mortality (death)
Timepoint [10] 421374 0
30 days post procedure
Secondary outcome [11] 421375 0
Need for further procedure (either dilation or fundoplication) - as noted from medical record
Timepoint [11] 421375 0
6-12 months post procedure
Secondary outcome [12] 421376 0
Complications:
Dysphagia
Gas-Bloating
Diarrhoea

As directly asked to patient in follow-up clinic (noted on medical record)
Timepoint [12] 421376 0
Within 6 months post procedure

Eligibility
Key inclusion criteria
Symptomatic gastro-oesophageal reflux, despite 2 months twice daily of PPI (proton pump inhibitor) use, and attempts to optimise lifestyle measures contributing to reflux events.
Confirmation of pathological reflux via 24-hr Oesophageal pH testing; either
• Acid Exposure Time >6%
• DeMeester Score >14.7
• Positive SAP (symptom association probability) (95%) with SI (Symptom index) >70%
Or:
• Los Angeles (LA) Grade C-D oesophagitis

High resolution oesophageal manometry performed in all patients to confirm the absence of major oesophageal motility disorders.

Consenting to participate in trial: willing to undergo either ARMA or surgical fundoplication
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Hiatus Hernia; Hill Grade IV or sliding hiatus hernia >2cm
Contra-indications to surgical fundoplication
- Previous major abdominal surgery precluding laparoscopy
- Previous gastric surgery
Major motility disorder on HR (high resolution) manometry assessment (as defined by Kahrilas et al)
- Minor motility disorder with functional impact (abnormal Ba swallow or solid food challenge)
Pregnancy

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 computerised randomisation

Patients will be randomised following consent to enter the trial. They will not be made aware of their allocation status until the day of their procedure.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer based randomisation 1:1
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Power calculations:
Power calculations were conducted using PASS version 11 (NCSS Statistical Software LLC, Utah, USA), with the change in GERD-HRQL score at 6 months being the pre-specified primary outcome for determining sample size. Sample size requirements were based on intention to treat (ITT) analysis of detecting non-inferiority of ARMA to fundoplication, with an a priori non-inferiority margin of delta </= 5 points for change in GERD-HRQL score. The results show that a minimum of 50 participants (25 participants per treatment group) was required to detect non-inferiority, with 80% power (ß = 0.2), at a one-sided statistical significance level of 5% (a =0.05). The SD of GERD-HRQL scores was estimated to be 7 points, based on a recent retrospective review of 100 patients.

Statistical analysis plan:

Statistical analysis will be performed using SAS version 9.4 (SAS Institute Inc, North Carolina, USA). The primary analysis will be conducted using an intention to treat (ITT) approach with baseline observation carried forward. The primary non-inferiority outcomes (improvements in GERD-HRQL score and pH measurements) will be analysed using the non-inferiority margin-adjusted one-tailed independent samples t-test. Secondary superiority outcomes will be assessed using the two-tailed independent t-test for continuous measurement with normal distributions confirmed by Shapiro-Wilk testing (p>0.05). Non-normally distributed continuous and ordinal data will be analysed using the two-tailed Mann-Whitney U-test, and categorical data using the two-tailed Fisher’s exact test. Data will be presented as mean +/-SD, median (IQR), number of participants (% of participants), unless otherwise stated, and p<0.05 will be considered significant.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
5/06/2023
Actual
12/01/2024
Date of last participant enrolment
Anticipated
2/06/2025
Actual
Date of last data collection
Anticipated
3/04/2028
Actual
Sample size
Target
50
Accrual to date
3
Final
Recruitment outside Australia
Country [1] 25370 0
New Zealand
State/province [1] 25370 0

Funding & Sponsors
Funding source category [1] 313548 0
Hospital
Name [1] 313548 0
Te Whatu Ora - Waitemata (North Shore Hospital)
Country [1] 313548 0
New Zealand
Primary sponsor type
Hospital
Name
Te Whatu Ora - Waitemata (North Shore Hospital)
Address
24 Shakespeare Road, Takapuna, Auckland 0620
Country
New Zealand
Secondary sponsor category [1] 315347 0
None
Name [1] 315347 0
Address [1] 315347 0
Country [1] 315347 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312729 0
Southern Health and Disability Ethics Committee
Ethics committee address [1] 312729 0
Ethics committee country [1] 312729 0
New Zealand
Date submitted for ethics approval [1] 312729 0
23/02/2023
Approval date [1] 312729 0
28/04/2023
Ethics approval number [1] 312729 0
2023 FULL 15109

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

Contacts
Principal investigator
Name 125698 0
Dr Cameron Schauer
Address 125698 0
C/O Gastroenterology Department
North Shore Hospital
124 Shakespeare Road, Takapuna, Auckland 0620
Country 125698 0
New Zealand
Phone 125698 0
+64210368637
Fax 125698 0
Email 125698 0
[email protected]
Contact person for public queries
Name 125699 0
Cameron Schauer
Address 125699 0
C/O Gastroenterology Department
North Shore Hospital
124 Shakespeare Road, Takapuna, Auckland 0620
Country 125699 0
New Zealand
Phone 125699 0
+64210368637
Fax 125699 0
Email 125699 0
[email protected]
Contact person for scientific queries
Name 125700 0
Cameron Schauer
Address 125700 0
C/O Gastroenterology Department
North Shore Hospital
124 Shakespeare Road, Takapuna, Auckland 0620
Country 125700 0
New Zealand
Phone 125700 0
+64210368637
Fax 125700 0
Email 125700 0
[email protected]

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?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
18771Study protocol    385660-(Uploaded-01-04-2023-13-17-22)-Study-related document.docx
18773Informed consent form    385660-(Uploaded-30-04-2023-14-10-35)-Study-related document.docx



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.