An international Multi-Interventional Registry study for chronic ileoAnal pouCh Leaks in UC

1. Summary
Rationale: Restorative proctocolectomy and pouch is nowadays the preferred option in patients with Ulcerative Colitis refractory to medical management and/or dysplasia and cancer. Quality of life of patients with pouches depends predominantly on proper function of the pouch. Inadequate function and long-term pouch failure are determined by the occurrence of in particular chronic anastomotic leaks.

Objective: The aim of the prospective registry study is to determine the functional anastomotic integrity rate 12 months postoperative after implementing multi-interventional program based on best peri-operative clinical care. Conjointly, we want to assess long-term functional anastomotic integrity rates for patients that received current peri-operative care by performing a retrospective cohort study.

Study design: The MIRACLE study is an international multicenter study assessing long-term functional anastomotic integrity rates in both a prospective cohort receiving a multi-interventional enhanced program and a retrospective cohort receiving standard care. The study will be carried out in referral centers for pouch surgery throughout Europe. The prospective registry study will be carried out for 2 years with 1 year follow up subsequently. The retrospective cohort study will include patients who underwent pouch-surgery between 2017 and 2019.
With an estimated inclusion of 250-300 pouches annually by the collaborative group, both the prospective and retrospective MIRACLE cohort will have a sample size of approximately 500 patients, adding up to 1000 patients in total.
Overall study duration will be 3 years for the primary endpoint and 3.5 years for the secondary endpoints.

Study population: Adult patients with diagnosed ulcerative colitis scheduled for a restorative proctocolectomy and pouch creation procedure will be included in the prospective cohort. For the retrospective cohort, all adult patients who underwent a proctocolectomy and pouch procedure between January 2017 and January 2019 will be included.

Study procedure: The multi-interventional program which will be implemented in the prospective registry study consists of preoperative oral antibiotics and enema, routine and, in case necessary, tailored lengthening measures of the mesentery, intraoperative control of pouch vascularization using IndoCyanin Green Fluorescence (ICG), early diagnosis and active assessment of the integrity of the anastomosis, and Endosponge Vacuum Assisted Closure (EVAC) of an anastomotic defect within 10-14 days after diagnosis. For both the prospective and retrospective cohort, MR imaging at a minimum of 12 months postoperative will be performed to assess anastomotic integrity if no cross sectional follow up imaging has been performed.

Main study endpoints: The primary endpoint of this study is long-term functional anastomotic integrity after pouch surgery for ulcerative colitis. The main study endpoint will be assessed by MR imaging a minimum of 12 months postoperative for both the prospective and retrospective study cohort. In case long term postoperative imaging is absent for patients in the retrospective cohort, prospective MR imaging is performed. Secondary endpoints include short- term functional anastomotic integrity, clinical pouch function, long-term quality of life, re-intervention rate, hospital stay length and death.Quality of life and pouch function will be assessed through questionnaires at baseline, 3,6, 12 and 18 months postoperative for the prospective cohort. For the retrospective cohort, questionnaires will be sent once after a minimum of 12 months postoperative.
MR imaging during long-term follow up after pouch surgery is considered best clinical care in order to assess long-term anastomotic integrity and used to measure the primary and secondary endpoints for this study.
The prospective cohort of the MIRACLE study can start in each hospital after training of the staff and full implementation of the five basic interventions. The primary endpoint for this cohort will be assessed by MR imaging 12 months postoperatively. For the patients in the retrospective cohort, MR imaging will be between 1.5-3.5 years if not done in regular follow up before. All those who will and can deliver the required data can participate. Prerequisite is data registration via the United Registries for Clinical Assessment and Research (UR-CARE) data platform.

The aim is to register standard and enhanced peri-operative care and determine anastomotic integrity separately for both cohorts.

Not applicable

1. Preoperative oral antibiotics and antibiotic enema of the rectal stump prior to the surgery
2. Routine and, if intraoperatively scored necessary, tailored lengthening measures of the mesentery
3. Intraoperative control of pouch vascularization using ICG coloring
4. Early diagnosis and active assessment of the integrity of the anastomosis.
a. Routine CRP-measurements at day 4 and 6 (after removal pouch catheter) in the non-diverted pouches with CT-scan with rectal contrast if any suspicion on a leak (elevated or rise in CRP. symptoms).
b. Routine CRP-measurements at day 4 in the diverted pouches with standardized pouch endoscopy 10-14 days after pouch creation if CT with rectal contrast has not been performed.
5. Endosponge vacuum assisted closure (EVAC) of the anastomotic defect aiming to close the defect within 10-14 days after diagnosis
6. MR assessment of the pouch after stoma closure preferably at one year to rule out any silent sepsis mimicking pouchitis or Crohn’s disease.