Clinical trial NCT02354287: Effectiveness of Cold Biopsy Forceps With Pre-lift for Complete Resection of Colonic Polyps ≤7mm in Size
Official title: Effectiveness of Cold Biopsy Forceps With Pre-lift for Complete Resection of Colonic Polyps ≤7mm in Size.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Colorectal Polyps
Lead sponsor: Gloucestershire Hospitals NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Olympus
First posted: 2015-02-03
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Residents from within Gloucestershire, United Kingdom whom have been referred for a Colonoscopy through either.

1. Bowel cancer screening program or outpatient referral
2. Outpatient clinics
3. Inpatient referral

Brief summary: There is no consensus method for removal of diminutive (5mm) to small(6-9mm) colorectal polyps at colonoscopy. Neither the European Society of Gastrointestinal Endoscopy or the American Society of Gastrointestinal Endoscopy have guidelines for the removal of these polyps, despite the fact that around 90% of lesions removed by polypectomy at colonoscopy are diminutive to small.

Multiple techniques are used for polyp removal, especially diminutive lesions. These include either forceps, both hot and cold, as well as snare with electrocautery or cold snare. Forceps utilises shearing force to grasp tissue and remove it, with the hot method passing a current through the grasper to essentially burn tissue. Snare is the use of a small metal loop placed and tightened at the base of polyps to cut through the tissue either straight away in a cold method or with electrocautery where a small current is passed through the loop to assist cutting through tissue. Surveys of Colonoscopists and Gastroenterologists in Australia and the United States show that the choice of method used for diminutive to small polyps is highly variable with cold snaring marginally favoured.Studies into polypectomy techniques are limited and it is clear that additional data and the review of polypectomy methods needs to be undertaken in order determine the optimal method for the removal of diminutive and small colorectal polyps.

A technique is used at the Gloucestershire National Health Service (NHS) trust involving a submucosal pre injection with a standard solution then the use of cold forceps for removal of polyps ≤7mm. This appears to be both very safe and highly effective method for the removal of these lesions compared to other techniques. No formal published studies have been completed to evaluate this method at national and international levels. We propose a study to evaluate the effectiveness, safety and costs of this method.

Detailed description: Hypothesis A pre injection and cold forceps technique for removal of polyps ≤ 7mm is safe and results in retrieval rates \>98% with complete histological resection \>90% of the time.

Objectives

1. Determine the histological complete resection rate (CRR) using a pre injection lift and cold forceps for polypectomy of polyps ≤7mm.
2. Determine the number of bites required for complete visual resection of these polyps and the time taken from the beginning of pre injection needle insertion till complete resection.
3. To determine the polyp retrieval rate of this method.
4. To record any complications from this technique.
5. To compare the CRR, number of biopsies for visual eradication, time taken, polyp retrieval rate and complication rate of this method to cold forceps alone and cold snare from previous studies.

Methods

Participants:

Sample size 150 polyps, anticipated to be captured in between 75 and 100 patients based on an average of 2 polyps per patient. There is no published data on this polypectomy technique and there is limited data on other diminutive to small polypectomy techniques. Other comparative published studies looking at polypectomy techniques for diminutive to small polyps have had polyp numbers between fifty four and one hundred and seventeen.The sample size of 150 polyps is an approximation based on the fact that it is an achievable figure within the scope of the project and local clinical service which should yield a relatively narrow confidence interval.

Colonoscopists 3 experienced Gastroenterologists (JA, TB, PD) working within the Gloucestershire NHS Trust, each having performed over 3000 colonoscopies. All Gastroenterologists are certified British Bowel Cancer Screening Program Colonoscopists. As the technique being studied is already well practiced within the trust the extra time required for each polyp included in the study is negligible.

Pathologist All Polypectomy specimens and EMR tissue will be examined by an expert Gastrointestinal Pathologist (NS) who will be blinded to the patient and colonoscopist details when examining specimens.

The additional work for the pathology department is negligible. It can be routine practice to take additional material for analysis if incomplete removal of the polyp is suspect. In the study all polyps will have this review. NS will provide consistency and also time to support us in this project.

Course of Action:

1. Patients will be consented to participate in the study prior to their procedure. Information regarding the study will be posted to the patient at least a week prior to their colonoscopy.
2. If patient agrees to participate details including age, sex and indication for scope will be recorded. This data will be recorded with a patient study number. The patients will be otherwise anonymised.
3. Data from each colonoscopy and polypectomy will be recorded, including polyp size, location, time for resection, bites required for complete visual resection (another study showed the median number of bites to be at 2 with range 1-5 ), overall withdrawal time and quality of bowel preparation at the time of the procedure. Any adverse events at the time of colonoscopy, polypectomy and EMR or at subsequent patient follow up 7 days post procedure will be recorded prospectively on form A (Appendix 1) and also reported to the Research and Development team within 7 days of the Investigators becoming aware of the adverse event.

3. All colonoscopies will be performed using Olympus 240 and 260 colonoscopes with magnetic endoscopic imaging and Narrow band imaging (NBI) available to the Colonoscopist if required.

5. The equipment used for each polypectomy and Endomucosal resection (EMR) of polypectomy site will include the following.

1. Needle for pre injection
2. Pre injection mix will include 19 ml gelofusine, 1ml 1:10000 adrenaline and 1ml indigo carmine.
3. Cold forceps with span of 6.8mm and capacity of 7.22mm3
4. Olympus snare master 10mm snare.

   6. Any complications relating to the polypectomy will be recorded. 7. Polyps ≤7mm will be included in the study if deemed appropriate by the colonoscopist. Polyps may be considered inappropriate if polyp location or appearance is not suitable for the technique being studied.

   8. These polyps will be resected with cold forceps after pre injection into the submucosa. Data related to this resection will be recorded as noted above.

   9. The polypectomy site will then be resected with EMR using conventional snare method to ascertain if there is any residual polyp tissue. This is the only additional step to the polypectomy process which would not otherwise take place. The risk from this step of an adverse event to the patient would be significantly less than the risk of complication from a therapeutic Colonoscopy which is between 0.05 and 0.07%. A maximum of 3 polyps per patient will be included for study analysis in order to ensure both patient and colonoscopist time at procedure does not differ significantly from what it would normally.

   10. Both EMR specimen and resected polyp tissue will be sent for histopathological evaluation by single expert Gastrointestinal Histopathologist who has kindly agreed to review the extra EMR tissue in his own time.

   11. Recruited patients will be called one-week post colonoscopy to ensure they do not wish to withdraw from the study and they have had no concerns post their procedure.

   Adverse Events As mentioned above the risk of adverse events related to the polypectomy technique being studied or the EMR of residual tissue is minimal.

   All adverse events (or medical occurrence) will be recorded in data collection spreadsheets. Any events classified as 'serious adverse events' (SAE) will be reported to the Research and Development Unit (RSDU).

   The following criteria will be used to assess the relationship (causality) of the adverse event to the polypectomy technique and EMR performed
   1. None: - The adverse event is definitely not associated with the investigational technique being used.
   2. Possible: - A causal relationship is possible when the adverse event follows a reasonable temporal sequence from the application of the intervention, but could have been produced by the patient's clinical state or other modes of treatment being administered to the patient.
   3. Probable: - The causal relationship is probable when the adverse event follows a reasonable temporal sequence from the application of the investigational technique. This is likely if the adverse event cannot be explained by the known characteristics of the patient's clinical state

   Adverse events will be assessed by one of the investigators who are qualified Gastroenterologists and managed accordingly.

   The severity of adverse events will be recorded using the following criteria:
   1. Mild: - Symptom(s) barely noticeable to the patient or does not make the patient uncomfortable. The AE does not influence performance or functioning.

      Prescription drugs are not ordinarily needed for relief of symptom(s).
   2. Moderate: - Symptom(s) of a sufficient severity to make the patient uncomfortable or require endoscopic intervention or other treatments.
   3. Severe: - Symptom(s) of a sufficient severity to cause the patient severe discomfort requiring subsequent treatment or require major endoscopic intervention, hospitalisation or surgery.

   A serious adverse event (SAE) includes adverse events that result in death, require either inpatient hospitalization or the prolongation of hospitalization, are life threatening, result in a persistent or significant disability/incapacity. Other important medical events, based upon appropriate medical judgement, may be considered Serious Adverse Events if a trial participant's health is at risk and intervention is required to prevent an adverse outcome.

   Dr Alex di Mambro FRCP (Gloucestershire NHS Trust Gastroenterologist) will evaluate, report and assist in patient management should there be a SAE. In no other way has she been involved in study development or will she be involved during the course of the study.

   All reports of serious adverse events (SAE) will be recorded on the SAE form for this trial and forwarded immediately to the Research \& Development Unit (RSDU). A copy of this form can be seen in the appendix 1. In the event of a SAE persisting greater then 24 hours another form will be submitted to the RSDU. Also, in the case of a persisting SAE the time of event resolution, patient death or discharge a subsequent form will be completed and submitted.

   Data recording and statistical analysis: All data will be recorded prospectively in a Microsoft excel spread sheet by the chief investigator (SO) and statistical analysis completed with SPSS version 16. Based on a target sample size of 150 polyps with 90% success rate the calculated 95% confidence interval will be 84.5-94.2%.

   Data storage: The collected data will be kept secure within the department of Gastroenterology and not shared with uninvolved persons. The data will be anonymised and the excel sheet the data is collected on will be password protected and not available to other individuals not involved with the study. All recorded data will be destroyed by the end of calendar year 2017 or once the anonymised results have been presented and published which is expected to be by the end of calendar year 2015.

   Results It is anticipated that results of this study will be completed for abstract submission for United European Gastroenterology Week by May 2015. This meeting will be held in Europe in October 2015. We will aim to publish this data in an international Endoscopic journal by late 2015. Results will be made available to our Bowel Cancer screening nurses who will be able to disseminate these results to various Bowel Cancer support groups.

   Funding

   Researchers and Time allocation The chief investigator has time (20hr/week) allocated into current Gloucestershire NHS Trust contract for education and development. Development of this study, data recording/entry and generation of an academic paper will all be undertaken in this time.

   Professor Neil Shepherd, Pathologist for this project has agreed to undertake the additional work of EMR tissue review in his own time.

   Additional time for colonoscopists will be for EMR of polypectomy site that is considered negligible in the course of a standard colonoscopy.

   Equipment As explained in the methods section minimal additional pieces of equipment are needed compared to the standard colonoscopy. Snares for EMR of polypectomy site will only be additional should a snare not have already been required for the removal of larger polyps during the course of the colonoscopy.

   Olympus will kindly provide the additional snares for the study. All other equipment such as pre injection solution, pre injection needle and cold forceps would normally be used in the course of colonoscopy and polypectomy.

Eligibility criteria: Inclusion Criteria:

* Patients from Cheltenham General Hospital and Royal Gloucestershire Hospitals that have been scheduled for colonoscopy through our outpatient clinics or inpatient consult service will be prospectively recruited prior to their Colonoscopy.

Exclusion Criteria:

* Patients will be excluded if:

  1. They are under the age of 18.
  2. They do not have capacity to consent for the Colonoscopy as determined at the time of procedural admission by the trained admitting endoscopy nurse. If a patient is deemed to lack capacity by the referring doctor or admitting nurse this will also be assessed by the colonoscopist. Both the colonoscopist and admitting nurses have been trained to assess capacity,that is whether a persons mind is affected at the time of the procedure in such a way that they are unable to make a decision. There are multiple reasons as to why an individuals brain or mind may be altered such as medications, mental illness or dementia.
  3. There is a history of Inflammatory Bowel Disease
  4. Identified coagulopathy with PT\>1.4 or thrombocytopenia with Platelets \<80 on any bloods collected within routine clinical practice within the past 4 weeks. This will not be an additional procedure and these bloods are routinely taken on patients where coagulopathy or thrombocytopenia is a concern such as patients on long term Warfarin or with chronic liver disease. These patients are identified by Endoscopy nursing staff in pre assessment work up. Routine haematology is not taken as part of a standard assessment for outpatient endoscopy.
  5. Taking dual anti platelet therapy or pharmacological anti coagulation.
  6. Bowel preparation is deemed poor by colonoscopist.

Primary outcomes:
measure: Histological complete resection rate (CRR) using a pre injection lift and cold forceps for polypectomy of polyps ≤7mm.
timeFrame: Within one week of patients colonoscopy
Secondary outcomes:
measure: The number of bites required for complete visual resection of these polyps and the time taken from the beginning of pre injection needle insertion till complete resection.
timeFrame: intraoperative during colonoscopy and analysed within one month of last patient recruitment
Other outcomes:
measure: The polyp retrieval rate of this method.
timeFrame: intraoperative during patient colonoscopy and analysed within one month of last patients recruitment.
measure: Immediate or delayed complications from this technique.
timeFrame: intraoperative and after one week.
measure: An overall comparison of this polypectomy method compared to other methods used for diminutive and small polyps.
timeFrame: 2 months post completion of recruitment.
Locations:
city: Cheltenham
country: United Kingdom
facility: Cheltenham General Hospital
state: Gloucestershire
Study officials:
affiliation: Advanced Endoscopy and Gastroenterology Fellow
name: Sam A O'Connor, FRACP
role: PRINCIPAL_INVESTIGATOR
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