Complete Histologic Resection of Adenomatous Polyps? (CARE)

• ClinicalTrials.gov Identifier: NCT01224444
• Recruitment Status: Completed
• First Posted: October 20, 2010
• Results First Posted: January 12, 2015
• Last Update Posted: January 12, 2015
• Sponsor: White River Junction Veterans Affairs Medical Center
• Collaborator: Dartmouth-Hitchcock Medical Center
• Information provided by (Responsible Party): Dr. Heiko Pohl, White River Junction Veterans Affairs Medical Center

Tracking Information

• First Submitted Date: October 19, 2010
• First Posted Date: October 20, 2010
• Results First Submitted Date: December 16, 2013
• Results First Posted Date: January 12, 2015
• Last Update Posted Date: January 12, 2015
• Study Start Date: May 2008
• Actual Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 30, 2014)

Percent of Incompletely Resected Adenomatous Polyps [ Time Frame: 1 year ]

Proportion of incompletely resected adenomatous polyps (5 to 20mm), defined by remaining adenomatous tissue in marginal biopsies after snare resection.

Original Primary Outcome Measures (submitted: October 19, 2010)

Primary Endpoint [ Time Frame: 1 year ]

• Proportion of remaining adenomatous tissue after adenoma resection of all sessile polyps between 5 and 20mm.

Current Secondary Outcome Measures (submitted: December 30, 2014)

Incomplete Adenoma Resection of Small and Large Adenomas [ Time Frame: 1 year ]

Comparison of the proportion of incompletely resected adenomatous polyps by size (5-9mm versus 10-20mm).

Original Secondary Outcome Measures (submitted: October 19, 2010)

Secondary Endpoint [ Time Frame: 1 year ]

• Comparison of the proportion of completely resected sessile adenomatous polyps by size (5-9mm versus 10-15mm)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Complete Histologic Resection of Adenomatous Polyps?
• Official Title: Complete Histologic Resection of Adenomatous Polyps? (Complete Adenoma REsection Trial - CARE Trial)

Brief Summary

Colorectal cancer is the second most common cause of cancer death in the US. Colonoscopy is considered the best test colorectal cancer screening. It allows resection of adenomatous polyps (a known cancer precursor) and thus, interrupt the adenoma-carcinoma sequence. Despite the potential benefit of screening colonoscopy recent studies have reported cases of colorectal cancers in a short interval after prior screening or surveillance colonoscopies. One possible cause of such interval cancers may be incomplete resection of adenomatous polyps and hence ongoing growth and cancer development in such lesions. Complete resection may be particularly important for polyps of at least 5mm in size as up 10% of such polyps higher risk lesions as villous adenoma, tubulovillous adenoma, high grade dysplasia, or early carcinoma.

Although adenoma resection of sessile and flat adenomatous polyps between 5 and 20mm is believed to be well standardized data on complete resection of adenomatous tissue are sparse. This may be related to the assumption that using a snare with electro-cautery will successfully remove the polyp and cauterize remaining marginal adenomatous tissue and hence completely remove and or destroy the lesion.

The investigators are interested in examining how often sessile adenomatous polyps between 5 and 20mm are completely removed using standard polypectomy snare. The investigation was also directed at a comparison between complete resection of polyps between 5 and 9mm and 10 and 20mm.

Detailed Description

All patients who present for a colonoscopy and meet inclusion and exclusion criteria will be asked to participate, and all patients with resectable polyps will be included. See also inclusion and exclusion criteria.

All patients will have undergone a regular bowel preparation with polyethylene glycol lavage with 4-6 L until clear rectal fluid is evacuated.

Polyp resection will be performed by experienced endoscopists (each with over 500 colonoscopies performed). All polyps between 5 and 20mm will be removed with an electro-cautery snare. Polyp size will be estimated using the snare catheter (2.5mm) or the snare diameter (10x20mm, 15x30mm, 20x20mm) before resection. The endoscopist will grade the difficulty of resection. Following the resection, the endoscopist will closely examine the resection margins. Biopsies will be taken from resection margins: 2 biopsies will be obtained from opposite margins for polyps 5-9mm, and 4 biopsies will be taken for polyps 10-20mm from all four quadrants of the resection margins. In case of assumed incomplete resection this will be documented and further (piecemeal) resections should be done, if this is not feasible, margins can be cauterized according to standard polypectomy resection (e.g. by argon beamer coagulation) after previous biopsy. Only those polyps that are found to be adenomatous polyps will be included in the analysis.

If polyp resection is complicated by bleeding (not self-sustained), no biopsies will be taken and any additional polyps that will be found during the remaining examination will be excluded from analysis. Any bleeding from the margins after polypectomy will be treated by endoscopic injection using diluted epinephrine (1:10.000).

A single research subject may have many eligible polyps. To avoid taking many biopsies, the investigators will not include more than 5 eligible polyps (the first 5 that are detected) per patient in the study.

Laboratory Analysis:

Polyps and biopsies will be sent to the pathology lab of each center. The polyps will be evaluated according to common practice. In addition information regarding resection margins will be provided for each polyp: R0= free of adenomatous tissue, R1=adenomatous tissue detected in the margin. This information is not routinely provided by the pathologist as there is so far no data whether this information is reliable. Only adenomatous polyps will be included in the analysis. Hyperplastic polyps will not be included. Biopsies will only be processed after the diagnosis of an adenomatous polyp was made. Biopsies will be evaluated for presence of adenomatous tissue. The additional impact for the pathology lab includes a) processing of biopsies belonging to the polyp specimens, and b) providing information on polyp margins. The VA pathology lab estimated the financial impact to be low and there will be no financial requests. The pathological diagnosis, including the reading of the biopsies, will become part of the medical record. If biopsies contain adenomatous tissue the patient will be ask to return for a follow-up colonoscopy within 1 year. This is within current standard of care to repeat a colonoscopy to assure complete adenoma resection.

• Study Type: Observational
• Study Design: Observational Model: Case-Only; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples Without DNA

Description:

Biopsies will be taken from resection margins: 2 biopsies will be obtained from opposite margins for polyps 5-9mm, and 4 biopsies will be taken for polyps 10-20mm from all four quadrants of the resection margins.

• Sampling Method: Non-Probability Sample
• Study Population: Participants eligible for recruitment are patients who present for a colonoscopy to the VAMC or DHMC Gastroenterology department conducting this study. Upon arrival for a scheduled colonoscopy patient records will be reviewed to determine eligibility.
• Condition: Adenomatous Polyps

Intervention

Other: standard polypectomy snare

Electrocautery snare resection of sessile colonic polyps

Study Groups/Cohorts

All adenomatous polyps

Standard polypectomy snare of adenomatous polyps (included serrated adenomas) from ≤5mm to ≤20mm.

Intervention: Other: standard polypectomy snare

• Publications *: Pohl H, Srivastava A, Bensen SP, Anderson P, Rothstein RI, Gordon SR, Levy LC, Toor A, Mackenzie TA, Rosch T, Robertson DJ. Incomplete polyp resection during colonoscopy-results of the complete adenoma resection (CARE) study. Gastroenterology. 2013 Jan;144(1):74-80.e1. doi: 10.1053/j.gastro.2012.09.043. Epub 2012 Sep 25. Erratum In: Gastroenterology. 2021 Oct;161(4):1347.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 30, 2014): 269
• Original Estimated Enrollment (submitted: October 19, 2010): 400
• Actual Study Completion Date: January 2013
• Actual Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Any patient ≥40 and <85 who presents for a colonoscopy and does not meet any of the exclusion criteria mentioned below will be asked to participate
• All patients who are found to have colonic polyp between 5 and 20mm in size will be included in the study

Exclusion Criteria:

• Pedunculated polyps (estimated stalk diameter < 50% polyp head diameter, stalk at least 5 mm)
• Any suspicion of perforation or deeper defects after polypectomy, irrespective whether treated or not.
• Post-polypectomy bleeding requiring hemostasis.
• Patients with known inflammatory bowel disease or active colitis
• Patients who are receiving an emergency colonoscopy
• Poor general health (ASA class>3)
• Patients on coumadin or with coagulopathy with an elevated INR ≥1.8, or platelets <50.
• Poor bowel preparation
• Patients who do not consent
• Pregnancy

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01224444
• Other Study ID Numbers: DMS-21237
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Dr. Heiko Pohl, White River Junction Veterans Affairs Medical Center
• Original Responsible Party: Heiko Pohl, MD, White River Junction VAMC
• Current Study Sponsor: White River Junction Veterans Affairs Medical Center
• Original Study Sponsor: Same as current
• Collaborators: Dartmouth-Hitchcock Medical Center

Investigators

• Principal Investigator: Heiko Pohl, MD; White River Junction VAMC, Dartmouth Medical School

• PRS Account: White River Junction Veterans Affairs Medical Center
• Verification Date: December 2014