Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12613000720718
Ethics application status
Approved
Date submitted
25/06/2013
Date registered
1/07/2013
Date last updated
25/07/2019
Date data sharing statement initially provided
25/07/2019
Date results information initially provided
25/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Hot avulsion versus argon plasma coagulation for the management of the non-lifting polyp: a multicentre, randomised controlled trial
Scientific title
For patients with non lifting polyps, is Hot Avulsion versus Argon Plasma Coagulation for removal of residual polyp tissue more effective.
Secondary ID [1] 282734 0
Nil known
Universal Trial Number (UTN)
U1111-1145-0110
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Colonic Polyps 289468 0
Condition category
Condition code
Oral and Gastrointestinal 289782 289782 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
Hot Avulsion is an endoscopic technique, which involves mechanical electrocoagulation and resultant avulsion of neoplastic tissue using a standard hot biopsy forceps.

This will be performed using a Hot Biopsy forceps by Boston Scientific or Olympus. The neoplastic tissue will be grasped in the forceps and then preferentially, EndoCut I (ERBE VIO 200/300, Effect 2/Timing 2/Other 3) will be delivered using a tapping technique. If neoplastic tissue does not avulse with application of current, gentle mechanical traction will be applied away from the bowel wall. In centres with older electrocautry systems (ERBE ICC 200), coagulation (Soft coagulation, 80 W) will be used instead with gentle mechanical traction away from the bowel wall. This process will be continued until all neoplastic tissue has been removed as deemed by the treating physician.
Intervention code [1] 287397 0
Treatment: Devices
Intervention code [2] 287433 0
Treatment: Other
Comparator / control treatment
Argon Plasma Coagulation is a medical endoscopic procedure that involves the use of a jet of ionised argon gas (plasma) that is directed through a probe passed through the endoscope. The probe is placed at some distance from the target lesion, and argon gas is emitted and then ionised by a high voltage discharge. High-frequency electrical current is then conducted through the jet of gas, resulting in coagulation of the target lesion on the other end of the jet.

Ablation of the target tissue using APC will be continued until all macroscopic neoplastic tissue has been successfully ablated as deemed by the treating physician.
Control group
Active

Outcomes
Primary outcome [1] 289865 0
Rate of macroscopic and histologic eradication of neoplasia at the first follow up colonoscopy.
Timepoint [1] 289865 0
12 months
Secondary outcome [1] 303420 0
The rate of macroscopic and histological eradication at 12 months
Timepoint [1] 303420 0
12 months
Secondary outcome [2] 303421 0
Number of procedures required to achieve eradication
Timepoint [2] 303421 0
At completion
Secondary outcome [3] 303422 0
Procedural complications (immediate and delayed bleeding, perforation, and serositis) occurring within 14 days of the polypectomy and cost
Timepoint [3] 303422 0
Within 14 days of polypectomy
Secondary outcome [4] 303423 0
Cost data abstraction sheets using pertinent data from outpatient and hospital records will be designed to determine the direct costs attributable to each arm. The calculation will consist of summing the costs of all endoscopy visits, laboratory, imaging, and complication-related treatment following randomisation for events whose onset is within a 14-day window after randomisation. Costs attributable to hospital stay and related in-hospital testing will also be recorded.
Timepoint [4] 303423 0
At completion

Eligibility
Key inclusion criteria
1. Referral for colonoscopic polyp (>= 20mm) removal or attending follow-up colonoscopy following complete or incomplete polyp removal and this deemed appropriate by a consultant gastroenterologist
2. Any polypectomy case where there remains visible neoplastic tissue after attempts at standard snare resection by an expert Endoscopist
3. Aged 18 years or above
4. Patient able to give signed Informed consent
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Any condition that precludes the patient from undergoing colonoscopy eg. severe co-morbidities, pregnancy
2. Patients having received Coumadin preparations, Clopidogrel within the prior 7 days, therapeutic dose of unfractionated heparin within 6h, low-molecular weight heparin within 12 h, or Dabigatran within the prior 2 days
3. Patients with known severe coagulopathy (INR > 2.0), bleeding diathesis or severe thrombocytopenia (platelet count < 50,000)
4. Patients in whom complete snare resection is possible
5. Polyp not deemed endoscopically resectable
6. Polyps with endoscopic features concerning for sub-mucosal invasion as assessed by an expert Endoscopist

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)
Provided the patient fulfills all inclusion criteria, informed consent will be obtained by a trained research assistant prior to randomisation. At the time of colonoscopy with patient still sedated, randomisation will be carried out when the identified polyp has failed removal using standard injection and snare techniques as determined by the primary Endoscopist. Depending on the assignment, the patient will either have HA or standard
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will take place at a central location. Assignments will be prepared in variable block sizes using computer-generated random numbers.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Parallel study but patients will be allowed to cross arms if failed treatement with two attempts in the assigned arm.
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
We base our primary outcome sample size calculation on an extrapolation from the previously published literature. According to standard binomial sample size calculation formulae, we require 80 patients per group assuming an incidence of polyp residual of 40% 1 in the APC group and 20% in the HA group (alpha = 0.05, beta = 0.20, two-tailed). As this will be a multicenter study, participating centres currently perform approximately 1000 polypectomies per year with an estimated non-lifiting EMR rate of 20%, we estimate an accrual period of 48 months with approximately 80 patients recruited yearly (assuming 20% of patients are eligible, 50% of patients consent to enter the trial and a combined 10% failure and drop out rate).

Primary analysis will be from an intention-to-treat viewpoint comparing the effectiveness of the two approaches. The treatment success and relative risk of residual disease in the two groups will be defined and 95% confidence intervals for the different proportions of patients with treatment success at 12 months will be calculated. Univariate data will be analyzed using a Chi-squared test.

In order to ensure that randomisation has succeeded and baseline characteristics and confounders do not differ between the two groups the following characteristics will be tabulated:
- Patient demographics
- High risk factor/s as detailed above
- Interventions performed As detailed above
Annual interim analysis is planned

Multivariate analysis to find independent predictors of who will benefit most from hot avulsion will also be carried out. The following variables will be included: age, gender, technique used, reason for failed conventional EMR, and size of residual polyp at time of first treatment.

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
8/07/2013
Actual
8/07/2013
Date of last participant enrolment
Anticipated
Actual
1/07/2018
Date of last data collection
Anticipated
Actual
1/07/2018
Sample size
Target
160
Accrual to date
Final
80
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 1159 0
Sir Charles Gairdner Hospital - Nedlands

Funding & Sponsors
Funding source category [1] 287508 0
Self funded/Unfunded
Name [1] 287508 0
Country [1] 287508 0
Primary sponsor type
Individual
Name
Dr Spiro Raftopoulos
Address
Department of Gastroenterology and Hepatology
Sir Charles Gairdner Hospital
Hospital Avenue
Nedlands, WA 6009
Country
Australia
Secondary sponsor category [1] 286246 0
Individual
Name [1] 286246 0
Dr Ian Yusoff
Address [1] 286246 0
Department of Gastroenterology and Hepatology
Sir Charles Gairdner Hospital
Hospital Avenue
Nedlands, WA 6009
Country [1] 286246 0
Australia
Secondary sponsor category [2] 286247 0
Individual
Name [2] 286247 0
Dr Donald Ormonde
Address [2] 286247 0
Department of Gastroenterology and Hepatology
Sir Charles Gairdner Hospital
Hospital Avenue
Nedlands, WA 6009
Country [2] 286247 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289483 0
Sir Charles Gairdner Group Human Research Ethics Committee
Ethics committee address [1] 289483 0
Sir Charles Gairdner Hospital
Hospital Avenue
Nedlands, WA 6009
Ethics committee country [1] 289483 0
Australia
Date submitted for ethics approval [1] 289483 0
Approval date [1] 289483 0
16/05/2013
Ethics approval number [1] 289483 0
2013-034

Summary
Brief summary
Endoscopic management of large colonic polyps is an increasingly utilised and accepted alternative to
surgery. Complete polyp removal after a single treatment session is high with a recent prospective study
reporting first-time success in 84% of patients presenting for endoscopic management.
The success rate of first time complete polypectomy is significantly lower when the lesion cannot be fully
excised utilising a standard injection and snare technique. This is more common in large rectal polyps,
polyps that have undergone partial or incomplete resection, and polyps that have been marked with SPOT
tattoo. All these scenarios result in submucosal fibrosis and therefore failed lift with standard submucosal
injection.
In this setting the traditional approach has been to resort to ablative techniques such as argon plasma
coagulation (APC) and snare tip coagulation (STC), however the use of APC has been identified as a risk
factor for residual adenoma at follow-up colonoscopy with a recent study showing an increase in residual
adenoma at follow-up from 17.5 to 39.5% (RR 2.25; 1.45-3.50, p=0.002).
Recently, the use of hot avulsion (HA) has been shown in a prospective pilot study, to be a safe and highly
effective technique for dealing with difficult non-lifting polyps (NLP).
Currently there is no published literature to guide effective management of the NLP. The proposed study
design is a randomised clinical trial comparing HA to APC (the current standard of care) for the management
of polyps that fail removal using a standard snare resection technique. We postulate that HA will result in a
significantly higher rate of complete polyp removal of the non-lifting polyp when compared to standard
therapy.
Patients undergoing colonoscopy for removal of large polyps (>20mm), polyps that have failed previous
resection, polyps that have previously been injected with SPOT tattoo or patients presenting for follow-up of
previously removed large polyps will be approach for inclusion in the study. Following commencement of
polypectomy, if the endoscopist fails to remove the polyp entirely using standard snare techniques, they will
be randomised to either HA or standard of care (APC).
The primary outcome measure of this study is the rate of macroscopic and histologic eradication of
neoplasia at the first follow up colonoscopy which is routinely performed at 4 months. The outcome variable
is dichotomous (residual or no residual) and will be expressed as a proportion. If patients fail removal at first
follow-up, a second treatment will be attempted. If at the second follow-up there is persistent polyp, this will
be considered a treatment failure and the treating physician will then be able to either cross arms or refer the
patient for surgical management.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 41042 0
Dr Spiro Raftopoulos
Address 41042 0
Department of Gastroenterology and Hepatology
Sir Charles Gairdner Hospital
Hospital Avenue
NEDLANDS, WA 6009
Country 41042 0
Australia
Phone 41042 0
+61893462031
Fax 41042 0
Email 41042 0
[email protected]
Contact person for public queries
Name 41043 0
Dr Spiro Raftopoulos
Address 41043 0
Department of Gastroenterology and Hepatology
Sir Charles Gairdner Hospital
Hospital Avenue
NEDLANDS, WA 6009
Country 41043 0
Australia
Phone 41043 0
+61893462031
Fax 41043 0
Email 41043 0
[email protected]
Contact person for scientific queries
Name 41044 0
Dr Spiro Raftopoulos
Address 41044 0
Department of Gastroenterology and Hepatology
Sir Charles Gairdner Hospital
Hospital Avenue
NEDLANDS, WA 6009
Country 41044 0
Australia
Phone 41044 0
+61893462031
Fax 41044 0
Email 41044 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?

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.