Title: Optimisation before Crohn’s surgery using Exclusive enteral Nutrition (OCEaN study)
Funder: Department of Health and Social Care

Abstract: Background: Crohn’s disease is a lifelong inflammatory illness that causes people to have severe stomach pains, chronic diarrhoea, and suffer weight loss. Sadly, there is no cure. It affects about half a million people in the UK. Crohn’s disease causes inflammation, ulceration, bleeding and inflammatory narrowing of the digestive system. People can have periods of good health (“remission”) as well as times when symptoms are more active (“flare ups” or “relapses”). Medications can help keep it in remission, but at least one third of people with Crohn’s disease will need surgery to remove part of their gut at some stage. Surgery does not cure the disease – it removes the part of the bowel which is causing the problem at the time - and Crohn’s disease often comes back gradually after surgery. _x000D_ New Treatment: Previous small studies suggest that a special liquid diet might help improve outcomes from Crohn’s surgery. This diet is called “exclusive enteral nutrition” (EEN) because it is the only form of food the patient takes for a period of time; in this case the weeks leading up to their operation. EEN might help people get better quicker after their operation and might make the operation safer and more straightforward, with less chance of complications afterwards. Previous studies on this were too small or not planned in advance to find out if the EEN treatment works. EEN is not offered routinely to patients at the moment because we don’t have a good study showing it works._x000D_ Study Design: We will recruit 618 patients due to undergo surgery for Crohn’s disease where the operation will involve removing or repairing part of the bowel. We will allocate them at random to receive either EEN for at least six weeks prior to surgery, or to continue with usual diet. _x000D_ Detailed information will be collected on how patients recover after their operation and how they feel after their operation. Outcomes will be assessed regularly after surgery, with the assessment of differences between the two groups at 6 weeks post-operation being of primary interest. We will also follow each patient up regularly for the next year to also see how quickly patients get back to normal life and to see if Crohn’s disease comes back more often in one group or another. _x000D_ Patient and Public Involvement: To work out what this study should focus on we brought together people who have already had Crohn’s disease surgery and/or experience with EEN on a number of zoom calls. We also surveyed a large number of patients to get their views. This information has been key in deciding how to design and run this study. Factors that mattered most to this patient group included: surgery going to plan; recovery from surgery; regaining quality of life; eating normally; being able to go out without worrying about where the nearest toilet is and avoiding stoma. Therefore, this is the information we will collect and use to decide if the treatment works or not. The research team includes a patient co-applicant._x000D_ Dissemination: We will write reports suitable for the general public with the help of our patient group and share on social media as well as publicise on patient support groups such as Crohn’s & Colitis UK. All findings will also be written as a formal research report and will be published in a freely accessible journal. If EEN is shown to be effective and make surgery safer, more effective, or easier to recover from, then widespread uptake can be anticipated across the NHS.

Lay abstract: To determine the impact of pre-operative Exclusive Enteral Nutrition (EEN) in patients undergoing surgery for Crohn’s Disease (CD). The primary objective is to evaluate whether 6 weeks of pre-operative EEN (a) reduces the risk of complications and/or (b) improves patient reported outcomes 6 weeks post CD surgery. Secondary objectives: to determine the effect of the intervention on a range of clinical, endoscopic and patient reported outcomes up to 12 months post-operatively and to determine the Cost-Effectiveness of the intervention._x000D_ Studies on the role of EEN in the pre-operative optimisation for CD surgery in adults suggest that EEN may avoid the need for steroids, reduce post-operative complications, reduce the need for stoma, reduce length of hospital stay and improve pre-operative parameters such as body mass index whilst reducing inflammatory markers such as c-reactive protein. However, these studies are retrospective and were not powered to demonstrate significance. No studies have looked at quality of life or patient reported outcomes with or without EEN in CD surgery. European Crohn’s and Colitis Organisation (ECCO) and European Society of Coloproctology joint statement recommends optimisation of nutrition preoperatively. However, they acknowledge there is not enough evidence to recommend routine use of EEN in adults. The 2020 ECCO review of IBD perioperative dietary therapy recognises that EEN shows promise as a preoperative optimisation strategy but do not recommend routine use due to lack of high-quality evidence. _x000D_ This prospective multicentre randomised study aims to define the role of EEN in the pre-operative management of CD. _x000D_ This will be a Multi-centre, Two arm, Parallel group, Open label, Pragmatic Randomised Controlled Trial, with an internal pilot and economic evaluation. 618 adult patients (>=16 years) undergoing planned surgery for small bowel and/or colonic CD will be randomised 1:1 to either six weeks of EEN prior to surgery or usual diet as per the local practice. Patients will be recruited in secondary care (tertiary referral centres and District General Hospitals) across the UK._x000D_ The study has dual primary outcomes which will be measured at six weeks post operation – the Crohn’s Life Impact Questionnaire is a CD patient-reported outcome assessing quality of life, and the Comprehensive Complication Index, which is a measure of post-operative complications. Secondary outcomes include length of hospital stay, length of bowel resected, number of anastomoses, need for ileostomy, leak rate, frequency of re-operation, clinical recurrence, patient adherence and acceptability of EEN and cost effectiveness._x000D_ The internal pilot will aim to recruit 100 patients from 20 sites over 9 months. Stop/Go criteria to full trial include recruitment rate, acceptance of and compliance with EEN and delays to operation._x000D_ The anticipated start date is February 2023. The project duration is 54 months. This includes a set-up phase of 6 months, recruitment of 29 months (including 9 month pilot), follow up of 13 months (includes 1 month for lag from randomisation to surgery), and 6 months for final data analysis and write up. _x000D_ Findings will be disseminated with the help of our patient panel, social media as well as Crohn’s & Colitis UK. We will present at national and international conferences and publish in open access journal. We will develop run webinars and family days to ensure findings are widely disseminated.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: ORAL AND GASTROINTESTINAL