Multi-interventional Program to Reduce Chronic Ileoanal Pouch Leaks in UC (MIRACLE)

June 23, 2021 updated by: London North West Healthcare NHS Trust
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.

Study Overview

Status

Not yet recruiting

Conditions

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.

Study Type

Interventional

Enrollment (Anticipated)

50

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Historic cohort
Other: Multi-interventional program cohort
  1. Preoperative oral antibiotics and antibiotic enema of the rectal stump prior to the surgery
  2. Routine and tailored lengthening measures of the mesentery
  3. Intraoperative control of pouch vascularization using ICG
  4. Early diagnosis and active assessment of the integrity of the anastomosis.

    1. 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).
    2. Routine CRP-measurements at day 4 in the diverted pouches with endoscopy 10-14 days after pouch creation.
  5. Endosponge vacuum assisted closure (EVAC) of the anastomotic defect aiming to close the defect within 10-14 days after diagnosis.
  6. MRI assessment of the pouch after stoma closure preferably at one year to rule out chronic sepsis mimicking pouchitis or Crohn's disease.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Leak rate
Time Frame: 1 year
Anastomotic integrity at one year postoperatively defined as the absence of presacral collections, anastomotic fistula and severe anastomotic stricture (not amenable for digital dilatation by rectal exam).
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Death
Time Frame: 1 year
Death
1 year
Cumulative anastomotic dehiscence rate
Time Frame: 18 month
Anastomotic insufficiency at 30 days, 6 months and 12 months defined as contrast extravasation and/or presacral perianastomotic fluid collections on CT scan or Anastomotic dehiscence at endoscopy.
18 month
QOL
Time Frame: 3,6,12 and 18 months
Quality of life and functional outcomes preoperatively and then 3, 6, 12 and 18 months post-operatively.
3,6,12 and 18 months
Protocol compliance
Time Frame: 18 month
Protocol compliance to any intervention
18 month
ICG
Time Frame: Operative
Change in management due to ICG
Operative
CRP
Time Frame: 30 days
Diagnostic accuracy of CRP for anastomotic leakage
30 days
EVAC
Time Frame: 18 month
Efficacy of EVAC with early transanal closure of the anastomotic defect
18 month
Stoma rate
Time Frame: 18 month
Permanent stoma rate at 18 months
18 month
Temporary ileostomy rate and duration
Time Frame: 18 month
Temporary stoma rate and stoma duration at 18 months
18 month
Complications
Time Frame: 1 year
Operative and post-operative complications within 30 days and 12 months (cumulative) of operation (using the Clavien-Dindo classification of surgical complications)
1 year
Hospital stay
Time Frame: 1 year
Hospital stay and total hospital stay at one year
1 year
Reintervention rate
Time Frame: 18 month
Reintervention rate
18 month
Readmission
Time Frame: 18 month
Overall and stoma-related readmission
18 month
Cost analysis of EVAC
Time Frame: 18 month
Cost analysis of anastomotic leakage and EVAC therapy
18 month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

July 1, 2021

Primary Completion (Anticipated)

July 1, 2022

Study Completion (Anticipated)

August 1, 2025

Study Registration Dates

First Submitted

June 23, 2021

First Submitted That Met QC Criteria

June 23, 2021

First Posted (Actual)

June 25, 2021

Study Record Updates

Last Update Posted (Actual)

June 25, 2021

Last Update Submitted That Met QC Criteria

June 23, 2021

Last Verified

June 1, 2021

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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