Extended mesenteric resection in Crohn’s disease: EXCEED Study Protocol—a blinded multicenter randomized controlled clinical trial (RCT)

Abstract

Background

Crohn’s disease presents a persistent challenge, particularly concerning disease recurrence in patients after previous intestinal resection. This recurrence often necessitates additional medical treatment or surgery, imposing a substantial burden on patients, healthcare systems, and society. Emerging evidence suggests that extended mesenteric excision may reduce recurrence.

The EXCEED study aims to investigate the mesentery’s influence on disease recurrence in Crohn’s disease.

Methods/design

Blinded multicenter randomized controlled clinical trial involving 208 patients. Patients will undergo randomization into two groups: Group A, the treatment group, will receive extended mesenteric resection, while Group B, the control group, will undergo the standard resection with the mesentery largely preserved. Stratification will occur based on preoperative medicinal treatment categories (none, immunological, biological) and the treatment facility at the time of inclusion. This randomized controlled trial will incorporate blinding procedures, with the understanding that due to the nature of this interventional surgical study, the operating surgeon cannot be blinded.

Primary endpoint is endoscopic signs of recurrence, defined as a modified Rutgeerts score > i2a, at the 12-month follow-up ileo-colonoscopy. Secondary endpoints include clinical recurrence at 6 and 12 months, as well as recurrence at 3 and 5 years postoperatively.

Tertiary endpoints are; impact of disease severity at the time of operation, according to the Montreal classification, impact of biological treatment on recurrence rates, postoperative complications burden according to the Comprehensive Complication Index (CCI), patient reported outcome through questionnaires (5Q-5D-5L and SIBDQ) and cost-effectiveness analysis.

Discussion

This study addresses a critical gap in Crohn’s disease literature, aiming to provide evidence on the impact of extended mesenteric excision in preventing disease recurrence, thereby contributing to enhanced patient outcomes.

Trial registration

ClinicalTrials.gov NCT06324838. Registered on 04/02/2024.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13063-025-09261-3.

Administrative information

Title {1}	Extended Mesenteric Resection in Crohn's Disease: EXCEED Study Protocol - a blinded multicenter randomized controlled clinical trial (RCT)
Trial registration {2a and 2b}	ClinicalTrials.gov (ID NCT06324838) 04/02/2024.
Protocol version {3}	Version 2
Funding {4}	Running costs as well as salary will be applied for through external funding, public as well as private funds. The study is not economically supported by the pharmaceutical industry. In case funding is obtained from the medical industry they will have no impact on the study design and publication of the results. Grants will be handled by Odense University Hospital. The account will be subjected to public audit. Patients will not receive remuneration. No authors have financial or other competing interest in regards to this study.
Author details {5}	Jens Kristian Bælum, MD, Department of Surgery, Odense University Hospital. (JKB) Jacob Rosenberg, MD, DMSc, Professor of Surgery, Herlev University Hospital. (JR) Pernille Larsen, MD, Department of Surgery, Vejle Hospital. (PL) Maiken Joergensen, PhD, Department of Gastroenterology, Vejle Hospital. (MJ) Hanna De La Croix, MD, PhD, Department of Surgery, Sahlgrenska University Hospital/Östra and Sahlgrenska Academy. (HLC) Eva Haglind, MD, PhD, Professor emerita, Department of Surgery, Sahlgrenska University Hospital/Östra and Sahlgrenska Academy. (EH) Eva Agenete, MD, Professor, Department of Surgery, Sahlgrenska University Hospital/Östra and Sahlgrenska Academy. (EA) BEAT-IBD research group (se acknowledgements) Jens Kjeldsen, MD, PhD, Professor, Department of Gastrointestinal Diseases, Odense University Hospital. (JK) Mark Bremholm Ellebaek, MD, Professor, Chief surgeon, Odense University Hospital. (MB)
Name and contact information for the trial sponsor {5b}	Mark Bremholm Ellebaek, MD, Professor, Head of pediatric and IBD surgery. Odense University Hospital, J.B. Winsløvs Vej 4, 5000, Odense C, Denmark, Mark.ellebaek1@rsyd.dk
Role of sponsor {5c}	The sponsor has the final authority over study design; collection, management, analysis, and interpretation of data; writing of the report; and the decision to submit the report for publication.

Introduction

Background and rationale {6a}

Crohn’s disease, marked by chronic gastrointestinal inflammation, presents challenges regarding management and due to recurrence of the disease. This study delves into the preventive potential of extended mesenteric excision in ileocecal resection to reduce disease recurrence in Crohn’s patients.

Commonly surfacing in young adults, Crohn’s disease often leads to surgical interventions, notably ileocecal resections, with a substantial portion of patients requiring additional surgical procedures within a decade due to persistent recurrence. Clinical recurrence rates after surgery have been reported from 36 to 86% ≤ 10 years of follow-up, and endoscopic recurrence rates are even higher [1]. In a recent multicenter study, recurrence after resection surgery could be detected endoscopically in 47.8%. Recurrence was defined as a modified Rutgeerts score > i2a, and the median time to follow-up endoscopy was 7 months postoperatively [2].

Post-surgery, vigilant monitoring through ileocolonoscopy at 6–12 months and tailored medical treatment based on endoscopic findings and the preoperative clinical presentation is important [1].

Mesenteric inflammation has been proposed as a significant contributor to the severity of Crohn’s disease, with the belief that leaving inflamed mesentery post-surgery is a risk factor for recurrence and disease progression [3]. Residual diseased mesentery heightens recurrence risk, emphasizing the need of addressing mesenteric involvement in surgical strategies [4]. Coffey et al.’s single-center retrospective cohort study reported that extensive mesenteric resection reduced recurrence risk and reoperation rates from 30 to 3% (mean follow-up time, 69.9 ± 48.47 months) [4, 5], emphasizing the need for a multicenter, prospective, and randomized trial.

Extended mesenteric resection differs from conventional resection by removing the mesentery alongside the bowel, addressing mesenteric inflammation as a driver of recurrence.

Currently, only one RCT has investigated this problem [6]. In this study, no significant difference in outcomes was found though this study has its limitations.

The EXCEED study aims to explore the impact of extended mesenteric excision on preventing Crohn’s recurrence.

Hypothesis: Extended mesenteric excision during ileocecal resection reduces postoperative recurrence compared to mesenteric-sparing resection.

Objectives {7}

The primary objective of this study is to examine whether extended excision of the inflamed mesentery in Crohn’s disease can reduce endoscopic recurrence after 12 months at the anastomotic site compared to standard mesenteric-sparing resection in ileocecal resection.

Clinical meaningfulness and effectiveness of the treatment are defined as a reduction of 20% in recurrence rates in the extended mesenteric resection group.

Trial design {8}

The EXCEED study is designed as a single blinded multicenter randomized controlled clinical trial (RCT). It is a two-arm superiority trial with a 1:1 allocation ratio. Participants will be randomized to either group A (extended mesenteric resection or group B (mesenteric sparring resection = Control)).

Methods: participants, interventions, and outcomes

Study setting {9}

The study will be anchored in The Research Unit for Surgery at The Department of Surgery Odense University Hospital (OUH). The Department of Surgery will collaborate with The Department of Gastrointestinal Diseases, and The Department of Pathology. All departments have agreed to participate in this project. All the clinically related study procedures are well-established at all participating hospitals.

Additionally, this study will be conducted as part of the Scandinavian Surgical Outcomes Research Group (SSORG) [7] with the participation of multiple surgical departments in Denmark, Sweden, and the other Nordic countries.

Eligibility criteria {10}

Inclusion criteria

• Patients above the age of 15 scheduled for planned or subacute ileocecal resection due to Crohn’s disease.

• Relevant endoscopy (ileo-colonoscopy with biopsies) and/or MRI with signs of Crohn within the last 12 months.

• Diagnosis of “simple” ileocecal Crohn’s disease (limited to ileocecal disease with a maximum of 40 cm of affected ileum), Montreal classification A2-A3, L1-L3, B1-B2 [8].

  • ◦ “Simple” B3 disease with local fistulation to mesentery or caecum can also be included. If fistulation requires more extended bowel resection than detailed above, they will be excluded.

Exclusion criteria

• Previous ileocecal resection.

• Need for acute intervention where preoperative work-up cannot be completed due to urgency.

• Inability to understand one of the Nordic languages.

• Inability to comprehend the purpose and design of the study.

• Pregnancy or lactation.

Who will take informed consent? {26a}

Informed consent will be obtained by a local study representative. Participant consent is obtained by the research team after an eligibility assessment. During the medical screening, the trial physician confirms eligibility, ensures informed consent, and answers any participant questions about the trial procedures. Written consent must be obtained. For minors < 18 years, both the minor and all legal guardians must sign a written consent form. If the minor turns 18 during the study period, a new consent form (as for adults) must be signed.

Additional consent provisions for collection and use of participant data and biological specimens {26b}

Biological specimens collected for this trial will be destroyed 3 months after use, with none stored for ancillary studies. De-identified participant data may be shared with other researchers, contingent on written permission from the Sponsor and adherence to all relevant ethics approvals. The data and funding source must be acknowledged. De-identified data may be stored in public repositories, ensuring participants cannot be identified. Sharing identifiable data requires the Sponsor’s written permission and local ethics and governance approvals. Identifiable data will be stored centrally at Odense University Hospital on a secure server. Only the PI at each center and the data manager will have access to this list.

Interventions

Explanation for the choice of comparators {6b}

The comparator (mesocolic sparing resection) has been chosen, as this is the standard resection method currently employed in the surgical treatment of ileo-cecal Crohn’s disease.

Intervention description {11a}

Surgical procedure and perioperative care

In all patients, the laparoscopic approach will be standard, but a conversion to open surgery for any reason will not be an exclusion criterion. The surgical procedure will adhere to the principle of minimal intestinal resection, but with a minimum of 5 cm of disease-free bowel on either side of the resection in both groups.

The type and configuration of the anastomoses will be left at the discretion of the operating surgeon, but a stapled side-to-side isoperistaltic anastomosis of at least 6 cm in length is encouraged, in accordance with ECCO guidelines [9].

The ileocolic vessels will be identified at their origin from the superior mesenteric vessels. The mesenteric resection margin will follow the ileal side of the ileocolic pedicle until the mesentery becomes visibly inflamed. At the level of inflammation, the ileocolic vessels or branches will be divided and the residual resection will follow the extent of inflammatory changes in the mesentery.

Any residual inflamed tissue left within the mesentery will be noted. The surgical specimen will be photo-documented and weighed after a standardized procedure. The Department of Pathology will evaluate the resection margins for signs of inflammation.

Standard mesenteric resection is defined as inflammation-guided resection. In this group only visible inflamed mesentery will be resected, avoiding central resection of the mesentery on the ileal side if it is not inflamed (see Fig. 1).

Fig. 1.

Surgical procedure. Green line marks the “standard” mesenteric resection. Black line marks the extended mesenteric excision

A full description of the surgical procedure can be found in Additional file 1.

Both treatment groups will receive standard postoperative care according to the routines of the hospital treating the patient.

Postoperative follow-up

Postoperative follow-up at 6 and 12 months consists of an ileo-colonoscopy, chart review, and questionnaires. The early follow-up at 6 months aims to detect early recurrence, enabling early medical treatment or other intervention. The 12-month follow-up will be the primary endpoint to determine recurrence. Long-term outcomes will be assessed through a chart review after 3 and 5 years, documenting reoperations, clinical symptoms, pharmacological use, and other complications.

Postoperative endoscopy

Endoscopy will be regarded as the gold standard for the detection of disease recurrence. The endoscopies, including bowel preparation and possible sedation, will be performed in accordance with local guidelines at each hospital. At least three sets of routine biopsies will be taken from the ileum (5 cm proximal to the anastomosis), anastomosis, and colon (5 cm below the anastomosis), respectively. A short video or photographs of each endoscopy will be saved for validation purposes. Lesions found during the endoscopy will be classified using the modified Rutgeerts score [10]. These will be stored in the study database on a secure server.

Patient-reported outcome

During the preoperative workup (baseline), the patient will be asked to complete 2 questionnaires (5Q-5D-5L and SIBDQ). Postoperatively, the patient will be asked to complete the same questionnaires at 6 and 12 months.

Criteria for discontinuing or modifying allocated interventions {11b}

The patient’s participation in the study, or refusal of consent, will not in any way affect his/her treatment. The patient can at any time withdraw consent without consequences for his/her possibilities for any treatment. In theory, the extended mesocolic excision may cause a risk of perioperative complications such as vascular lesions or extended intestinal resection. In colorectal cancer surgery, the complete mesocolic excision (CME) procedure has been widely accepted. This procedure uses the same resection margins close to larger vessels. Two large RCT studies have reported on complications to CME resections, one of which shows more intraoperative vascular lesions in the CME group vs. non-CME, but surprisingly more seriousClavien-Dindo grade > 3a complications in the non-CME group, while the other study shows similar morbidity rates between the groups [11].

Should unexpected and/or undesired complications arise during the project, the project will immediately be discontinued, and the issues will be evaluated by the project responsible medical doctors and the management of the Research Unit for Surgery.

Strategies to improve adherence to interventions {11c}

To improve adherence to the intervention, several strategies will be implemented. Participants will receive clear, written and verbal instructions about the intervention at the start of the study. Regular follow-up visits and scheduled check-ins (in person or via phone/email) will be conducted to monitor progress, address concerns, and provide encouragement. Reminder systems, such as text messages or calendar alerts, may be used to prompt compliance. Additionally, participants will have access to study staff for questions or support throughout the intervention period, helping to maintain engagement and adherence.

Relevant concomitant care permitted or prohibited during the trial {11d}

Postoperative medical prophylaxis assessment is not explicitly detailed in the current protocol, though it will be acknowledged. The treating physician will determine the postoperative medical therapy, typically maintaining pre-operative medication.

Provisions for post-trial care {30}

The patients will be informed that the study is covered by the existing rules covering patient study participation, pertaining to each country. Thus, patients are insured in case of adverse effects causing harm or requiring additional treatment. Regardless of participation and randomization status, all patients will receive standard post-trial care according to best medical practice.

Outcomes {12}

Primary outcome is endoscopic signs of recurrence, defined as a modified Rutgeerts score > i2a, at the 12-month follow-up colonoscopy.

Secondary outcomes are:

• Endoscopic recurrence at 6 months: Defined as a modified Rutgeerts score > i2a.

• Histological recurrence at 6 months: Granulomas, chronic inflammation, distortion of the crypts, lymphocyte infiltration,

• Endoscopic recurrence at 12 months entire Rutgeerts scores.

• Clinical recurrence (i.e., recurrence of symptoms, resumption of medical treatment, or surgery) at 6 and 12 months.

• The possible use of Artificial Intelligence (AI) areal calculation tool to assess differences in the area of removed mesenteric tissue.

• Chart review at 3 and 5 years postoperatively.

  • ◦ Endoscopic/clinical recurrence, re-operations, medicinal treatment.

• The impact of disease severity at the time of operation, according to the Montreal classification, on recurrence rates.

• Impact of biological treatment on recurrence rates.

• Intraoperative complications (vessel lesions, larger resection than planned, bowel perforation).

• Postoperative complications according to the Comprehensive Complication Index (CCI) [12], assessed by chart review at 30 days.

• Quality of life—Patient reported outcome through questionnaires (5Q-5D-5L and SIBDQ score) preoperative, 6 and 12 months.

• Cost-effectiveness—a health-economy study of treatment costs, societal costs. This will be performed if the trial’s primary endpoint shows a significant difference between groups and will be performed in collaboration with one/more health economists.

Participant timeline {13}

Participant timeline is specified in Fig. 2 (attached).

Fig. 2.

Participant timeline

Sample size {14}

Risk of postoperative recurrence in Crohn’s disease has been investigated extensively. The estimated risk of recurrence varies depending on the definition (e.g., endoscopically, clinically or need of reoperation). In a recent multicenter study, recurrence could be detected endoscopically in 47.8% [10]. Recurrence was defined as a modified Rutgeerts score > i2a, and median time to follow-up endoscopy was 7 months.

Assuming a 50% recurrence rate in the control group and a decrease to 30% recurrence in the intervention group we required 93 patients in each arm to obtain a power of 80% at a 5% significance level.

To account for drop-outs and to be able to do a supplementary analysis, only investigating patients who received postoperative prophylactic medication, 10% is added to keep 80% power and the sample size is therefore increased to 104 patients in each arm. Thus, a total of 208 patients is to be included.

A supplementary analysis will include only patients receiving postoperative prophylactic medication to harmonize treatment groups and strengthen clinical interpretation.

Recruitment {15}

Patients scheduled for ileocecal resection for Crohn’s disease and fulfilling the inclusion criteria will be approached by a local study representative and informed about the purpose and design of the study. They will be asked for their participation in the study and must give written consent. This will be done in the hospital outpatient clinic at each participating hospital. Patients in need of expedited surgery due to severe symptoms will be included prior to surgery, if they fulfill the inclusion criteria. This will take place after the patient has been informed about the need for surgery. The information will be given in a calm environment and will be given both orally and in writing. Patients admitted for subacute surgery will receive the same information while in the ward. The patient will have the possibility to involve relatives or other lay persons in the information and discussion of the project. The patient will be given the possibility to further discuss the project with the clinical responsible researcher either by phone or face-to-face at the outpatient clinic and have at least 24 h to consider his/her participation in the study. The patient’s consent to participate in the study must be documented in the patient’s electronic medical record prior to any investigations being performed. By giving consent, the patient will allow investigators direct access to their medical records and obtain information on health-related conditions that are necessary for the conduction of the project and for audit and/or monitoring purposes as they may be obliged to perform.

If participants, at any time, wish to withdraw consent, all data related to that subject will be deleted.

A screening-log will be kept on those who are not willing to participate and those who drop out, to account for participation bias.

Assignment of interventions: allocation

Sequence generation {16a}

Eligible participants will be randomly assigned to either Group A (extended mesenteric excision) or Group B (standard resection with preserved mesentery), as seen in Fig. 1. Stratification will occur based on preoperative medicinal treatment categories (none, immunological, biological) and the treatment center at the time of inclusion. Although stratification is only performed by preoperative medication and treatment center, other factors (age, sex, disease duration, comorbidities) will be adjusted for in regression analyses. Variable block size randomization is used to minimize predictability and potential bias in treatment allocation. The randomization process will assign each subject to Group A or B using the RedCap™ Randomization Module hosted by Open Patient data Explorative Network (OPEN) [13].

Concealment mechanism {16b}

The description of the surgery within the patient chart will follow a standardized format, with the exception of the resection details. Where the two treatment methods diverge, a predefined, standardized text referencing the study will be inserted. thus ensuring concealment for all other than theatre staff, surgeon and study group.

Implementation {16c}

Upon enrollment in the study, which is done locally, the local lead investigator will have the ability to randomize participants using the RedCap™ Randomization Module.

Assignment of interventions: blinding

Who will be blinded {17a}

This randomized controlled trial will incorporate blinding procedures. Treatment group and resection method will not be stated in the patient chart. Patients, local investigators (except local lead), ward staff and outcome assessors (performing postoperative endoscopies) will be blinded. Due to the nature of this interventional surgical study, the operating surgeon and theatre staff cannot be blinded. However, rigorous measures will be implemented to ensure the blinding of both patients and all other participants involved in patient treatment.

Pathology requisitions will not mention whether an extended resection has been performed and the report will follow a standardized procedure.

These procedural steps are implemented to prevent confirmation bias, ensuring that both postoperative care and follow-up are not affected by the type of surgical procedure performed.

Procedure for unblinding if needed {17b}

In cases where breaking blinding becomes necessary for reasons such as patient safety or other concerns, each treatment facility will designate a local lead investigator empowered to make such decisions.

Data collection and management

Plans for assessment and collection of outcomes {18a}

Data will be collected using electronic case report forms in REDCapTM hosted by Odense Patient Data Explorative Network (OPEN). Some variables will be auto-calculated, e.g. time between surgery and follow-up and total Rutgeerts score. Data monitoring personnel will review and resolve any issues.

Plans to promote participant retention and complete follow-up {18b}

Participant retention and minimizing loss to follow-up will be promoted by Text/SMS reminders prior to follow-up. Questionnaires will be available for both electronic and hard-copy completion. Patients will not receive remuneration.

Data management {19}

All data is stored (OPEN) in accordance with current GDPR guidelines. The project is subject to a data processor agreement (Data Processing Agreement, DPA). Data collection and storage will be performed at Odense University Hospital. Personal information is secured at each hospital. The protocol writing committee will also act as the data monitoring committee.

Confidentiality {27}

Each participant receives a unique study identifier at screening for data de-identification. Only authorized personnel access identifiable data, which is disclosed to third parties only with participant permission or as required by law. Study data shared with third parties for research will be de-identified.

Plans for collection, laboratory evaluation and storage of biological specimens for genetic or molecular analysis in this trial/future use {33}

This study will not collect or store any biological material for further studies. Only a standard pathological evaluation of the resected tissue will be done. Tissue will be destroyed as per protocol for the local center.

Statistical methods

Statistical methods for primary and secondary outcomes {20a}

Demographics

Exchangeability between the two operation groups will be assessed using descriptive statistics based on baseline variables. Categorical variables will undergo analysis via chi-square test or Fischer’s exact test, following Cochran’s rule. Continuous and discrete variables will be analyzed using either independent t-tests or Wilcoxon rank-sum tests, depending on variable distribution, as determined by quantile-quantile plots. Results will be presented in baseline tables, alongside margin plots. Baseline variables include age, sex, height, weight, disease duration, Montreal classification, smoking status, prior medication, and treatment center.

Outcome analysis

Main outcome

A chi-square or Fisher’s exact test will be used to compare the proportion of patients with endoscopic recurrence between the intervention and control groups.

Logistic regression will be used to adjust for potential confounding variables, including biological treatment, disease severity, anastomosis type, patient age (in 5-year age groups), sex and treatment center. Co-variates will be selected based on clinical relevance and the results of univariate analysis.

Secondary outcomes

• Complications: Univariate analysis will be conducted on individual types of complications (abscess, leakage, etc.), as well as complications as a whole. Fisher's exact or Chi-square test will be used to compare treatments depending on the number of observations. For complications with sufficient number of events, a logistic regression adjusting for the same possible confounders as the main outcome will be performed.

• Surgical differences: Difference in the duration of the operative time is assessed using bootstrapping to report median time as well as difference with confidence interval. Defined as skin incision to skin closure.

• Quality of life is expressed as overall score values with a natural minimum and maximum. To handle repeated measurements, linear mixed-effects regression, with a random intercept for each patient, will be used. Given potential variation in quality of life between groups over time, a likelihood ratio test (using the Kenward-Roger approximation) will be conducted to assess treatment effects across all time points. For estimating differences between operation groups at each time point, mean differences with confidence intervals will be estimated. In a supplementary analysis we will adjust the mixed effect model for time varying covariates, describing complications and medical treatment during follow-up.

• Cost effectiveness analysis: Calculating the costs based on average treatment expenses and sick-leave cost between treatment groups compared with bootstrapping to take into account a skewed distribution of cost. Thus a societal cost-effective anaylsis evaluation differences in cost over the study period of 5 years.

Assumptions of normality and equal variance will be controlled using Q-plots and t-tests. Goodness of fit for logistic regression will be done using the Hosmer-Lemeshow test.

P-values less than 0.05 will be considered statistically significant. Statistical calculations will be conducted using Stata software.

Secondary outcome analysis is considered explorative; the results should be interpreted with caution, recognizing the inherent limitations of exploratory investigations and the potential for findings to be hypothesis-generating rather than confirmatory.

A full data-analysis plan will be formed prior to data processing to investigate possible confounders.

Interim analyses {21b}

Two interim analyses will be done after data completion (12-month follow-up) of the first 100 patients. One analysis will primarily be focused on any adverse surgical outcomes (safety analysis). Any unexpected outcome of this analysis will be discussed in the research safety committee in regard to study changes or the discontinuation of the study. The safety committee is a team of researchers and statisticians not involved in the study. They have the power to discontinue the study if deemed unsafe. Pre-specified boundaries for early efficacy, or evidence of excess surgical morbidity for early termination will be applied prior to interim analysis.

Furthermore, an interim analysis focusing on the efficacy of the treatment will be done after a 12-month follow-up of the first 100 patients. This will be done to re-evaluate the sample size. Sample size will be corrected, if needed, to avoid a type-I error.

Methods for additional analyses (e.g., subgroup analyses) {20b}

Please see section {20a}.

Methods in analysis to handle protocol non-adherence and any statistical methods to handle missing data {20c}

A per-protocol analysis will be undertaken that excludes participants who did not adhere to the protocol. An intention-to-treat analysis will be done on participants with some missing data. Missing data will be handled by multiple imputation, last observation carried forward or complete case analysis, depending on the variable that is missing data. Sensitivity analyses with complete case analysis will also be performed.

Plans to give access to the full protocol, participant level-data and statistical code {31c}

After the end of the study, when all data has been analyzed, an anonymized dataset will be uploaded to an open repository for further use. The full study protocol and data dictionary may be provided by the study investigators, on application, if this is in accordance with ethics approval.

Data will be retained locally until the end of the study (5-year follow-up). After the end of the study, de-identified data will be uploaded to “The Danish National Library Repository,” which is an open access repository for further use.

Oversight and monitoring

Composition of the coordinating centre and trial steering committee {5d}

The coordinating center is The Research Unit for Surgery at The Department of Surgery Odense University Hospital (OUH). The Trial Steering Committee will be composed of the primary investigator, sponsor, and local center leads. Monthly or bi-monthly meetings will ensure smooth communication and workflow.

Composition of the data monitoring committee, its role and reporting structure {21a}

The data monitoring committee will consist of two experienced researchers not involved in the study, a statistician, as well as a data manager with extensive expertise in data management. The researchers and statistician will be found outside of the Surgical Research Unit. Meetings will be held if necessary but close communication will be upheld throughout the study.

An external quality and data committee consisting of other researchers will be formed in order to ensure a non-biased oversight.

Adverse event reporting and harms {22}

Reported adverse events and harms will be discussed within the safety committee detailed above and appropriate action will be taken depending on the event. Meetings in the safety committee will not be held with a fixed interval, but any adverse event will be discussed promptly if they arise.

Frequency and plans for auditing trial conduct {23}

Trial conduct will be audited periodically by an independent monitoring body not involved in the study’s execution or sponsorship. Audits will assess compliance with the protocol, Good Clinical Practice (GCP), and regulatory requirements. The frequency will be determined based on trial risk and progress.

Plans for communicating important protocol amendments to relevant parties (e.g., trial participants, ethical committees) {25}

All significant protocol amendments will be communicated to relevant parties by the steering committee. Amendments to the research protocol are submitted for ethics committee approval and then to site-specific authorities before implementation. Changes to the protocol will also be submitted on ClinicalTrials.gov. Approved changes are updated in the eCRF and trial files, and communicated directly to study investigators and relevant staff.

Dissemination plans {31a}

The principal investigators are committed to communicating the results—negative, positive, or inconclusive results—at local, national, and international scientific meetings. The findings will be published in well-established, international peer-reviewed open access journals.

Discussion

Recent insights highlight the role of mesenteric inflammation in disease recurrence, opening avenues for targeted interventions. There is currently only one RCT that has investigated the same problem [6]. In this study, no significant difference in recurrence rates was found.

We believe that this RCT study, with a large study population, will contribute significantly to the emerging body of evidence regarding this topic. This study will employ a longer follow-up endoscopy regimen (12-month follow-up), thus ensuring that early follow-up endoscopies will not interpret postoperative lesions as recurrence.

This study addresses a critical gap in Crohn’s disease literature, aiming to provide evidence on the impact of extended mesenteric excision in preventing disease recurrence, thereby contributing to enhanced patient outcomes.

Though limitations include possible variability between surgeons and differences in follow-up adherence. strengths include the multicenter design, blinded outcome assessment, and long-term follow-up.

Trial status

This is protocol version 3, completed 15/10/2025. Recruitment began 01/02/2025, with anticipated completion by 01/02/2028. Primary endpoint results are expected in 2029 following 12-month follow-up.

Abbreviations

CD

Crohn’s disease

MRI

Magnetic resonance imaging

OPEN

Odense Patient data Explorative Network

SSORG

Scandinavian Surgical Outcomes Research Group

OUH

Odense University Hospital

RCT

Randomized controlled trial

AI

Artificial Intelligence

Authors’ contributions {31b}

JKB is the lead investigator; he conceived the study and led the proposal and protocol development. MB will act as sponsor and has contributed greatly to the proposal and protocol development. JK, EA, EH, and JR contributed to the study design and to the development of the proposal. All authors read and approved the final manuscript. BEAT-IBD research group at Odense University hospital is a research group focusing on advanced inflammatory bowel disease research. Besides the authors mentioned above, the following members have also contributed to the formation of this study: Mark Ainsworth, Casper Steenholdt, Helen Schultz, Malene Larsen and Anders Mark Christensen.

Funding {4}

Open access funding provided by University of Southern Denmark Please see table on page 3. Documentation for funding has been provided to the journal.

Data availability {29}

The final dataset will be stored at Odense University Hospital. Only the trial steering committee will have full access to the dataset. The project is subject to a data processor agreement (Databehandleraftale, DBA).

Declarations

Ethics approval and consent to participate {24}

This study is approved by the Danish Research Ethics Committee (Reg. Nr. 110039).

Consent for publication {32}

Consent for publication will be obtained from all participants prior to inclusion in the study. Participants will be informed about the use of anonymized data in publications and presentations, and explicit permission will be documented in the informed consent form.

Competing interests {28}

The authors declare that they have no competing interests.