Study of the Kono-S Anastomosis Versus the Side-to-side Functional End Anastomosis

Study Overview
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Brief Summary
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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
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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 months between the groups. The secondary aim is to evaluate the postoperative recurrence of CD using the Rutgeerts score at 12-18 and 60 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 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 Methods Design: This will be a multi-center randomized prospective trial with 338 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 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, and 60 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, and 60 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. post-operative endoscopic recurrence of CD using the Rutgeerts score at 12-18 months and 60 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 60 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 60 months. 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, and at 60 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. This is a qualitative evaluation.

Official Title
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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

Conditions
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Crohn's Disease

Intervention / Treatment
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* Other: side-to-side functional end anastomosis
* Other: Kono-S analstomosis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with Crohn's ileitis or ileocolitis requiring initial surgical resection. Age of 18 years and older, male and female All Phenotypes of Crohn's diisease will be included: nonpenetrating (B1), stricturing (B2), and penetrating (fistulating) (B3), according to the Vienna classification The patients can be on any medications coming into surgery, including prior anti- tumor necrosis factor(TNF) therapy. Exclusion Criteria: Patients under 18 years of age Patients with recurrent Crohn's Pregnant patients 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. Patients with Crohn's disease extending to the cecum and ascending colon Patients who will need preventive postoperative medical treatment Patients that need change of surgical procedure as per the surgeon at the time of the intraoperative abdominal evaluation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomized to undergo either the Kono-S anastomosis or the side-to-side functional end anastomosis.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: side-to-side functional end anastomosis<br>side-to-side functional end anastomosis creation | Other: side-to-side functional end anastomosis<br>* type of anastomosis<br>|
| Active Comparator: Kono-S<br>antimesenteric functional side-to-side handsewn anastomosis, known as the Kono-S anastomosis | Other: Kono-S analstomosis<br>* antimesenteric anastomosis<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-operative remission of Crohn's disease between 3 and 6 months after surgery | Endoscopic remission with a Rutgeert score between 3 and 6 months in order to determine if the Kono-S procedure is more likely to prevent post-operative recurrence of Crohn's disease compared with the side-to-side functional end anastomosis. Endoscopic remission is defined as a Rutgeerts score of 0, 1, or 2a at 3-to-6 months post-procedure colonoscopy. | 3-6 months after surgery | 
| Number of subjects with surgical recurrence at 60 months | Number of anastomoses in need of surgical revision for Crohn's disease recurrence after the initial index surgery. | 60 months after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-operative remission of Crohn's disease between 12 and 18 months and at 60 months after surgery | Endoscopic remission with a Rutgeerts score at 12 to 18 and 60 months in order to determine if the Kono-S procedure is more likely to prevent post-operative recurrence of Crohn's disease compared with the side-to-side functional end anastomosis. An endoscopic Rutgeerts score of 2b or higher will be considered a recurrence. | 12-18 and 60 months after surgery | 
| Work Productivity and Activity Impairment (WPAI) due to Crohn's disease | Work Productivity and Activity Impairment (WPAI) is a validated 6-item questionnaire that measures the amount of absenteeism and presenteeism due to CD during and activity impairment the 7 days prior to administration. It consists of 6 questions with the following domains: 1) employment status; 2) hours missed due to CD; 3) hours missed due to other reasons; 4) hours actually worked; 5) the degree to which CD affected productivity while working from 0 (no effect) to 10 (maximum impairment); and 6) the degree to which CD affected regular activities from 0 (no effect) to 10 maximum impairment ). All six question' domains will be reported and compared between the groups. Between the groups and within patients, changes will be evaluated. The mean score annual variability in each domain will be evaluated. | up to 60 months | 
| Health-Related Quality of Life using the Short Inflammatory Bowel Disease Questionnaire for Crohn's disease(10 questions) | Validated questionnaire to evaluate the quality of life in IBD patients. The short Inflammatory Bowel Disease Questionnaire (SIBDQ) is a 10-item shortened version of the original IBDQ, which was 32 items. Measures quality of life as measured in four domains, bowel symptoms, emotional health, systemic systems, and social function. SIBDQ score ranges between 10 and 70 points. QUOL is considered to be slightly (60-70 points), moderately (45-60 points), or severely impaired (10-45 points). In our study, the cut-off for relevant impairment of QUOL < 60 points. | up to 60 months | 
| Clinical disease activity measured by Harvey Bradshaw Index | Harvey Bradshaw Index is a marker of clinical disease activity. The following score grading system will be used to determine the clinical disease activity: Remission < 5 Mild disease 5-7 Moderate disease 8-16 Severe disease >16 | up to 60 months | 
| Time to surgical recurrence between Group1 and Group2 | Time to surgical recurrence between Group1 and Group2 measured in months from the index surgery | up to 60 months | 
| Focus Group | Patient 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. | up to 60 months | 
| Medication therapy type | Medication therapy for Crohn's disease after the index surgery. We will monitor the type of medications patients receive after surgery. The following five types of medications will be recorded: Biologics, Immunosuppressants, Corticosteroids, Anti-Inflammatory, and Antibiotics. | up to 60 months | 
| Readmission rates between Group1 and Group2 | Number of readmission due to Crohn's disease after the index surgery | up to 60 months | 
| Mortality rate | Number of patient expired after the index surgery | up to 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Crohn's recurrence