Clinical trial NCT04939025: Multi-interventional Program to Reduce Chronic Ileoanal Pouch Leaks in UC
Official title: Multi-interventional Program to Reduce Chronic Ileoanal Pouch Leaks in UC
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Ulcerative Colitis
Keywords: ileoanal pouch, IPAA, pouch, ulcerative colitis, leak
Lead sponsor: London North West Healthcare NHS Trust
Sponsor class: OTHER
First posted: 2021-06-25
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: The MIRACLE study is an international multicenter clinical effectiveness study, whereby the current local practice (control cohort) will be evaluated, and subsequently compared to the results after implementation of the multi-interventional program (intervention cohort).
Primary purpose: PREVENTION

Brief summary: The objective of this quality improvement project is to increase the one year anastomotic integrity rate in patients having had completion proctectomy and pouch reconstruction for Ulcerative Colitis by the routine and quality controlled implementation of a multi-interventional program thereby improving long-term pouch function and survival.

Detailed description: Ulcerative colitis is an inflammatory bowel disorder that affects predominantly young patients interfering with their social, family and professional life's (Ungaro, Mehandru, Allen, Peyrin-Biroulet, \& Colombel, 2017). When the disease is moderate to severe, it is difficult to control medically even in the era of the biologic treatment. Colectomy rates are reported to be as high as 50% after 5 years in patients admitted with a severe exacerbation (Duijvis et al., 2016; Thorne et al., 2016). In a modified two (colectomy first followed by completion proctectomy and pouch) or three stage procedure (colectomy first followed by completion proctectomy and pouch with diverting ileostomy, finally stoma closure) a proctocolectomy is done and continuity can be restored with a ileoanal pouch (Sahami, Buskens, et al., 2016; Zittan et al., 2016). These are the preferred options for the majority of our patients. Alternatives are proctocolectomy with definitive end-ileostomy or a continent ileostomy.

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 chronic anastomotic leaks, chronic pouchitis and a delayed diagnosis of Crohn's disease in and around the pouch (Lightner et al., 2017). The latter two diagnoses, Crohn's disease and chronic pouchitis are in an important number in fact misdiagnosed chronic leaks (Garrett et al., 2009; van der Ploeg, Maeda, Faiz, Hart, \& Clark, 2017). Long-term pouch failure rates (pouch excision or secondary diversion of the pouch) add up to more than 1 out of 10 at 10 years (Ikeuchi et al., 2018; Lightner et al., 2017; Mark-Christensen et al., 2018). These data represent the results of expert centers, so real life data are probably worse. Chronic leaks are late sequalae leaking anastomosis which has been inadequately treated; misdiagnosed or diagnosed too late to treat successfully.

Although many centers publish more favorable figures, the true rate of anastomotic leakage of ileoanal pouches probably varies from 10-20% (Sahami, Bartels, et al., 2016; Sossenheimer et al., 2019; Widmar et al., 2019). There is an important underreporting of the leaks. If the pouch is diverted, the leak will only become apparent prior to ileostomy closure when the anastomosis is tested. Even testing the anastomosis is not 100% accurate accounting for a number of misdiagnosed leaks. These misdiagnosed and delayed diagnosed leaks are generally not included in series reporting short term results (Santorelli, Hollingshead, \& Clark, 2018; Sossenheimer et al., 2019; Widmar et al., 2019).

For all these reasons it is of great importance to prevent anastomotic leakage when creating a ileoanal pouch and if it happens, to solve the problem as soon as possible.

Numerous risk factors have been identified for anastomotic leakage. The most important factors are tension on the anastomosis, inadequate vascularization of the pouch, an unfavorable microbiome and the use of immunosuppressive drugs (steroids, immunomodulators, biologic treatments). By staging the restorative proctocolectomy, the negative impact of immunosuppressive drugs on anastomotic healing are avoided because at the time of the pouch creation the drugs are weaned for a long period. Other factors including anastomotic technique and anastomotic perfusion are modifiable surgical factors. A more recently described pathophysiological mechanism relates to the intestinal microbiome (Alverdy, Hyoju, Weigerinck, \& Gilbert, 2017). Apparently, this holds true for small bowel surgery as well (Lesalnieks, Hoene, Bittermann, Schlitt, \& Hackl, 2018).

Proper management of a leak comprises early diagnosis and immediate and adequate management. Sequential CRP measurement and early investigation of the integrity of the anastomosis are key for early diagnosis, particularly in a diverted anastomosis which might not be symptomatic (Adamina et al., 2015; Warschkow et al., 2012).

The current management of the leak usually involves a diverting ileostomy, if not performed primarily, in combination with passive drainage of the abscess cavity via transanal or transcutaneous route. This approach showed to be relatively ineffective leading to a pouch failure rate of 20%, and if resolved to a worse pouch function (Garrett et al., 2009; Lightner et al., 2017).

Endosponge vacuum assisted closure (EVAC) of the anastomotic leak on the contrary showed to have a very high success rate and to prevent long-term pouch dysfunction and failure (Bemelman \& Baron, 2018; Gardenbroek et al., 2015; Verlaan et al., 2011; Weidenhagen, Gruetzner, Wiecken, Spelsberg, \& Jauch, 2008).

There is minimal risk to patients as there is no introduction of a novel technique, rather this study is an amalgamation of published improvements in pouch surgery pre, intra and post-operatively to reduce the leak rate at one year.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of Ulcerative Colitis
* Diagnosis of Crohn's disease limited to the colon without any history of perianal disease
* Modified two or three stage restorative proctocolectomy
* Age above 18
* Able to fill in questionnaires in local language and to come to out-patient-clinic visits;

Exclusion Criteria:

* Known allergy to ICG, or iodide allergy.
* Pregnancy
* Redo pouch operation
* Age under 18

Primary outcomes:
measure: Leak rate
timeFrame: 1 year
Secondary outcomes:
measure: Cumulative anastomotic dehiscence rate
timeFrame: 18 month
measure: QOL
timeFrame: 3,6,12 and 18 months
measure: Protocol compliance
timeFrame: 18 month
measure: ICG
timeFrame: Operative
measure: CRP
timeFrame: 30 days
measure: EVAC
timeFrame: 18 month
measure: Stoma rate
timeFrame: 18 month
measure: Temporary ileostomy rate and duration
timeFrame: 18 month
measure: Complications
timeFrame: 1 year
measure: Death
timeFrame: 1 year
measure: Hospital stay
timeFrame: 1 year
measure: Reintervention rate
timeFrame: 18 month
measure: Readmission
timeFrame: 18 month
measure: Cost analysis of EVAC
timeFrame: 18 month
Other outcomes:
Locations:
Study officials:
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