Clinical trial NCT03256240: Study of the Kono-S Anastomosis Versus the Side-to-side Functional End Anastomosis
Official title: Prospective Randomized Study of the Kono-S Anastomosis Versus the Side-to-side Functional End Anastomosis in the Prevention of Post-operative Recurrence of Crohn's Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Crohn's Disease
Keywords: Crohn's recurrence
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
Collaborators: name: Crohn's and Colitis Foundation
First posted: 2017-08-21
Enrollment: 550
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized to undergo either the Kono-S anastomosis or the side-to-side functional end anastomosis.
Primary purpose: PREVENTION

Brief summary: This study proposes a randomized prospective study comparing the Kono-S anastomosis to the standard side-to-side anastomosis.This will be a multi-center randomized prospective trial. Patients with Crohn's ileitis or Crohn's ileocolitis requiring resection will be randomized to undergo either the Kono-S anastomosis or the side-to-side functional end anastomosis.

Detailed description: Study Aim:

* The primary aim of this study is to compare the postoperative recurrence of CD using the Rutgeerts score at 3-6 months between the novel Kono-S anastomosis (Group1) and side-to-side functional end anastomosis (Group2) and surgical recurrence rate at 60 and 120 months between the groups.
* The secondary aim is to evaluate the postoperative recurrence of CD using the Rutgeerts score at 12-18, 60 and 120 months between the groups; time to surgical recurrence between Group1 and Group2 measured in months from the index surgery, yearly Crohn's disease surgical therapy impact using the Work Productivity and Activity Impairment (WPAI) questionnaire; yearly Health-Related Quality of Life using the Short Inflammatory Bowel Disease Questionnaire, to evaluate before surgery, and yearly after the surgery up 60 months the patient perception of illness measured by The Brief Illness Perception Questionnaire, (a 9-item questionnaire) score between the groups, to evaluate disease activity yearly using Harvey-Bradshaw Index and monitor medication therapy, readmission rates, and mortality rates through the 60 months follow-up, and utilize Focus Groups from national and international study sites to evaluate patient's perspectives on surgical treatment, patients' goals of surgical treatment, and surgical treatment's personal and social impacts, patient perspective on nutrition; and caregiver perspective on surgical treatment, to evaluate histologic predictors for endoscopic and clinical remission in Crohn's Disease after ileocecal resection using the histological scores from the surgical pathology margin evaluation, to evaluate the differences in the histological mucosal healing between Kono-S and Side- to Side anastomosis measured by the histological score between the groups using the modified Global Histology Activity Score (Modified) between the groups

Methods

Design: This will be a multi-center randomized prospective trial with 400 subjects. Patients with Crohn's ileitis or Crohn's ileocolitis requiring initial resection will be randomized to undergo either the Kono-S anastomosis or the side-to-side functional end anastomosis.

Patients will be randomized into two Groups:

Group 1: Kono-S anastomosis vs. Group 2: side-to-side functional end anastomosis.

The purpose of this study is to compare the postoperative recurrence of Crohn's disease between the Kono-S procedure and the side-to-side functional end anastomosis and to evaluate the surgical recurrence rate at 60 and 120 months between the groups.

In any intestine surgery, after the sick portion of the bowel is removed, the intestinal tract is restored by reconnecting the healthy ends together. The new connecting line is called anastomosis and could be created in a variety of ways by the surgeon. This study will compare two different intestinal connections called Kono-S anastomosis and the traditional side-to-side functional end anastomosis. Initial studies have demonstrated that the Kono-S anastomosis has prevented endoscopic evidence of the post-operative recurrence of Crohn's disease at greater rates than the traditional side-to-side functional end anastomosis.

Follow-up: Patients will be discharged on no prophylactic treatments, and they will be followed post-operatively at 3 to 6, 12 to 18, 60-, and 120 months with a colonoscopy to assess for endoscopic recurrence. The mucosa will be graded with the Rutgeerts score for postoperative recurrence. All colonoscopies are part of the standard treatment. All patients will have also standard 30 days, 3 to 6, 12 to 18, 24, 36-, 48-, 60-, 72-, 84-, 96-, 108-, and 120 months follow-ups by phone call, through medical records, or during the postoperative clinic visit.

Follow-up Care: Patients with a Rutgeerts score at 3-to-6 months of:

* 0, 1, or 2a will be followed prospectively with or without introducing medical treatment at the discretion of the gastroenterologist.
* above \>2a will initiate medical therapy for Crohn's disease
* Should the patient's symptoms warrant, medical treatment can be initiated at any time at the discretion of the gastroenterologist. This is a standard of care
* Colonoscopic images (still color photos acceptable) will be shown to a gastroenterologist blinded to the goal of the study for determination of the Rutgeerts score in addition to the initial evaluation by the sites endoscopists.
* post-operative endoscopic recurrence of CD using the Rutgeerts score at 12-18-, 60-, and 120 months between the groups. An endoscopic Rutgeerts score of 2b or higher will be considered a recurrence.
* Time to surgical recurrence between Group1 and Group2 measured in months from the index surgery
* Work Productivity and Activity Impairment (WPAI) questionnaire (a 6-item questionnaire that measures the amount of absenteeism and presenteeism due to health problems) will be administered annually for up to 120 months.
* Health-Related Quality of Life using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ) (a 10-item shortened version of the original IBDQ, measuring the quality of life in four domains: bowel symptoms, emotional health, systemic systems, and social function) will be administered annually for up to 120 months.
* The Brief Illness Perception Questionnaire, (a 9-item questionnaire) score measuring the patient perception of illness before surgery, at 24-, 36-, 48-, 60-, 72-, 84-, 96-, 108-, and 120-months post-procedure.
* Harvey Bradshaw Index as a marker of clinical disease activity will be used. This will be recorded before the procedure (baseline), at 3 to 6 and 12-18 months, 24-, 36-, 48-, 60-, 72-, 84-, 96-, 108-, and 120-months post-procedure.
* Other monitoring- monitor medication therapy, readmission rates, and mortality rates annually through the 60 months of follow-up between the groups
* Focus groups from national and international study sites to evaluate patients' perspectives on surgical treatment, patients' goals of surgical treatment, and surgical treatment's personal and social impacts, patient perspective on nutrition; and caregiver perspective on surgical treatment. This is a qualitative evaluation.
* surgical pathology margin evaluation will be used to assess for histologic predictors for endoscopic and clinical remission in Crohn's Disease after ileocecal resection
* The differences in the histological mucosal healing between Kono-S and Side- to Side anastomosis measured by the histological score between the groups using the modified Global Histology Activity Score (Modified) between the groups at 60 months.

Eligibility criteria: Inclusion Criteria:

1. Patients with Crohn's ileitis or ileocolitis requiring initial surgical resection.
2. Age of 18 years and older, male and female
3. All Phenotypes of Crohn's diisease will be included: nonpenetrating (B1), stricturing (B2), and penetrating (fistulating) (B3), according to the Vienna classification
4. The patients can be on any medications coming into surgery, including prior anti- tumor necrosis factor(TNF) therapy.

Exclusion Criteria:

1. Patients under 18 years of age
2. Patients with recurrent Crohn's
3. Pregnant patients
4. Patients with more than one non-contiguous site of active disease, thus requiring multiple resections or additional bowel sparing procedures at the time of surgery.
5. Patients with Crohn's disease extending to the cecum and ascending colon
6. Patients who will need preventive postoperative medical treatment
7. Patients that need change of surgical procedure as per the surgeon at the time of the intraoperative abdominal evaluation.

Primary outcomes:
measure: Post-operative remission of Crohn's disease between 3 and 6 months after surgery
timeFrame: 3-6 months after surgery
measure: Number of subjects with surgical recurrence at 60 months
timeFrame: 60 months after surgery
measure: Number of subjects with surgical recurrence at 120 months
timeFrame: 120 months after surgery
Secondary outcomes:
measure: Post-operative remission of Crohn's disease between 12 and 18 months, at 60-, and 120 months after surgery
timeFrame: 12-18, 60, and 120 months after surgery
measure: Work Productivity and Activity Impairment (WPAI) due to Crohn's disease
timeFrame: up to 120 months
measure: Health-Related Quality of Life using the Short Inflammatory Bowel Disease Questionnaire for Crohn's disease(10 questions)
timeFrame: up to 120 months
measure: Clinical disease activity measured by Harvey Bradshaw Index
timeFrame: up to 120 months
measure: Time to surgical recurrence between Group1 and Group2
timeFrame: up to 120 months
measure: Focus Group
timeFrame: up to 120 months
measure: Medication therapy type
timeFrame: up to 120 months
measure: Readmission rates between Group1 and Group2
timeFrame: up to 120 months
measure: Mortality rate
timeFrame: up to 120 months
measure: Surgical Pathology Margins
timeFrame: at surgery
measure: Mucosal Healing
timeFrame: 60 months after surgery
measure: Mucosal Healing from colonoscopy biopsies
timeFrame: 60 months after surgery
measure: The Brief Illness Perception Questionnaire
timeFrame: up to 120 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Oklahoma City
country: United States
facility: University of Oklahoma
state: Oklahoma
city: Dallas
country: United States
facility: Baylor Scott & White Research Institute
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Leuven
country: Belgium
facility: University Clinics Gasthuisberg Herestraat
city: Helsinki
country: Finland
facility: Helsinki University Hospital
city: Würzburg
country: Germany
facility: Universitätsklinik Würzburg
state: Wurzburg
city: Berlin
country: Germany
facility: Charité Campus Benjamin Franklin
city: Mannheim
country: Germany
facility: Theresien Hospital and St. Hedwigs Clinic gGmbH
city: Rozzano
country: Italy
facility: Humanitas University Hospital
state: Milan
city: Florence
country: Italy
facility: Azienda Ospedaliero-Universitaria Careggi
city: Naples
country: Italy
facility: Policlinico University Hospital
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
Study officials:
affiliation: Weill Medical College of Cornell University
name: Fabrizio Michelassi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Weill Medical College of Cornell University
name: Koianka Trencheva, Dr.PH,BSN,MS
role: STUDY_DIRECTOR
References:
citation: Kono T, Ashida T, Ebisawa Y, Chisato N, Okamoto K, Katsuno H, Maeda K, Fujiya M, Kohgo Y, Furukawa H. A new antimesenteric functional end-to-end handsewn anastomosis: surgical prevention of anastomotic recurrence in Crohn's disease. Dis Colon Rectum. 2011 May;54(5):586-92. doi: 10.1007/DCR.0b013e318208b90f.
citation: Kono T, Fichera A. Kono-S anastomosis for Crohn's disease: narrative - a video vignette. Colorectal Dis. 2014 Oct;16(10):833. doi: 10.1111/codi.12722. No abstract available.