Kono-S Versus Standard Bowel Reconnection After Crohn's Resection

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.

Study Aim: * The primary aim of this study is to compare the postoperative recurrence of CD using the modified 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. Evaluate histologic features in surgical specimen collected at the index surgery as predictors for endoscopic, clinical, and surgical recurrence after ileocecal resection for CD. To evaluate the histological mucosal healing at 60 months between the novel Kono-S anastomosis (Group1) and side-to-side functional end anastomosis (Group2) using Global Histology Activity Score and The Inflammatory Bowel Disease-Distribution, Chronicity, Activity \[IBD-DCA\] score. * The secondary aim is to evaluate the postoperative endoscopic recurrence of CD using the modified 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, anastomotic strictures, readmission rates, and mortality rates through the 120 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 long-term psychosocial impact and nutrition challenges, and to evaluate the differences in the histological/mucosal healing between Kono-S and Side-to-Side anastomoses. Methods Design: This will be a multi-center randomized prospective trial with 500 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 (control group). 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 modified 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: * All participating sites follow the same endoscopic evaluation protocol at 3-6, 12-18, 60, and 120 months, using the modified Rutgeerts score for grading the endoscopic recurrence * 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 at the discretion of the gastroenterologist. * 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 * 3 Colonoscopic images (still color photos acceptable) are taken to ensure standardized evaluation of the anastomoses and 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, and for additional analyses. * post-operative endoscopic recurrence of CD using the modified 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, postoperative morbidity and mortality rates annually through the 120 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 long-term psychosocial impact and nutrition challenges. 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.

Organization

Weill Medical College of Cornell University

Organization class

Other

Organization study ID

1303013645

Lead sponsor

Weill Medical College of Cornell University

Sponsor class

Other

Enrollment type

Estimated

Allocation

Randomized

Intervention model

Parallel

Primary purpose

Prevention

Masking

None

Who is masked

Not provided

Standard age groups

Adult, Older Adult

This information can identify a possible match, conflict, or item needing confirmation. Only the study team can determine eligibility.

1. Primary outcome

   Post-operative endoscopic remission of Crohn's disease between 3 and 6 months after surgery

   Time frame: 3-6 months after surgery

   Endoscopic remission with a modified Rutgeerts 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 modified Rutgeerts score of 0, 1, or 2a at 3-to-6 months post-procedure colonoscopy.

2. Primary outcome

   Number of subjects with surgical recurrence at 60 months

   Time frame: 60 months after surgery

   Number of anastomoses in need of surgical revision for Crohn's disease recurrence after the initial index surgery.

3. Primary outcome

   Number of subjects with surgical recurrence at 120 months

   Time frame: 120 months after surgery

   Number of anastomoses in need of surgical revision for Crohn's disease recurrence after the initial index surgery.

4. Primary outcome

   Mucosal Healing GHS

   Time frame: 60 months after surgery

   Mucosal Healing from colonoscopy biopsies using the modified Global Histology Activity Score (Modified) score between the groups. Global Histology Activity Score (GHAS) is a widely used tool that grades biopsies of the ileum and colonic segments. The score has 8 domains and includes the presence of architectural changes, degree of chronic, neutrophilic and eosinophilic inflammatory infiltration in lamina propria, presence of intraepithelial neutrophils, epithelial damage, mucosal defects, presence of granulomas, and the extent of inflammation (proportion of biopsy specimens affected). Each domain is scored independently, and the total score is the sum of all individual scores, ranging from 2 (being the lowest meaning no histological activity) to 16 (being the highest meaning high histological disease activity).

5. Primary outcome

   Mucosal Healing IBD-DCA

   Time frame: 60 months after surgery

   Mucosal Healing from colonoscopy biopsies using The Inflammatory Bowel Disease-Distribution, Chronicity, Activity \[IBD-DCA\] score between the groups. The score is validated and has 3 domains: 1) Distribution of the disease; 2) Chronicity of the disease; and 3) Activity of the disease. Each domain of the IBD-DCA is scored as one of 0 (normal), 1 (mild), or 2 (moderate to severe) based on the presence of established histological findings and the domains are separately reported. Distribution \[D\] 0=Normal 1. \< 50% of tissue affected per same biopsy site 2. ≥ 50% of tissue affected per same biopsy site Chronic features \[C\] 0=Normal 1=Crypt distortion and/or mild lymphoplasmacytosis 2=Marked lymphoplasmacytosis and/or marked basal plasmacytosis Activity features \[A\] 0=Normal 1. Two or more neutrophils in lamina propria in one high-power field \[HPF\] and/or intraepithelial neutrophils \[any number\] 2. Crypt abscesses, erosions, ulcers

6. Primary outcome

   Surgical Pathology Margins

   Time frame: at surgery

   Histological evaluation of the surgical pathology margin evaluation for presence or absence of disease

7. Secondary outcome

   Post-operative endoscopic remission of Crohn's disease between 12 and 18 months, at 60-, and 120 months after surgery

   Time frame: 12-18, 60, and 120 months after surgery

   Endoscopic remission with a modified Rutgeerts score at 12 to 18, 60-, and 120 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.

8. Secondary outcome

   Work Productivity and Activity Impairment (WPAI) due to Crohn's disease

   Time frame: up to 120 months

   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.

9. Secondary outcome

   Health-Related Quality of Life using the Short Inflammatory Bowel Disease Questionnaire for Crohn's disease(10 questions)

   Time frame: up to 120 months

   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.

10. Secondary outcome

    Clinical disease activity measured by Harvey Bradshaw Index

    Time frame: up to 120 months

    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

11. Secondary outcome

    Time to surgical recurrence between Group1 and Group2

    Time frame: up to 120 months

    Time to surgical recurrence between Group1 and Group2 measured in months from the index surgery

12. Secondary outcome

    Focus Group

    Time frame: up to 120 months

    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, patient perspective on nutrition, long-term psychosocial impact and nutrition challenges, and caregiver perspective on surgical treatment.

13. Secondary outcome

    Medication therapy type

    Time frame: up to 120 months

    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.

14. Secondary outcome

    Readmission rates between Group1 and Group2

    Time frame: up to 120 months

    Number of readmission due to Crohn's disease after the index surgery

15. Secondary outcome

    Mortality rate

    Time frame: up to 120 months

    Number of patient expired after the index surgery

16. Secondary outcome

    The Brief Illness Perception Questionnaire

    Time frame: up to 120 months

    The Brief Illness Perception Questionnaire, (a 9-item questionnaire) score with the nine items rated on a scale from 0 (minimum) to 10 (maximum), with higher scores indicating a more threatening perception of the illness. The total score is calculated by summing the scores of all eight items, with a possible range of 0-80. Higher scores indicate worse illness perception.

17. Secondary outcome

    Postoperative Morbidity

    Time frame: within 30 days after surgery

    Postoperative morbidity is defined as any deviation from the normal postoperative recovery course occurring within 30 days after surgery, as documented in daily in-hospital checks, clinical documentation records, imaging, laboratory results, interventional notes, or surgeon assessment, and presented as a binary outcome- "Yes" or "No".

18. Secondary outcome

    Postoperative Morbidity

    Time frame: up to 120 months

    Postoperative morbidity is defined as any deviation from the normal postoperative recovery course occurring up to 120 months after surgery, as documented in daily in-hospital checks, clinical documentation records, imaging, laboratory results, interventional notes, or surgeon assessment, and presented as a binary outcome- "Yes" or "No".

This study also lists 9 locations outside the United States. They are not shown here.

First posted

Aug 21, 2017

Primary completion

Jul 31, 2030

Overall completion

Dec 31, 2036