Clinical trial NCT06241170: Comparing Surgical Approaches for Crohn's Disease Recurrence
Official title: Mesentery Guided Resection Versus Traditional Ileocolic Bowel Resection in Reducing Early Endoscopic Recurrence Rate After Ileocolic Crohn 's Disease Surgery:a Prospective, Multicenter, Randomized Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Endoscopic Recurrence Rate
After Ileocolic Crohn 's Disease Surgery
Keywords: endoscopic recurrence rate
ileocolic Crohn 's disease surgery
Mesentery Guided Resection
Lead sponsor: Sixth Affiliated Hospital, Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: First Affiliated Hospital, Sun Yat-Sen University
First posted: 2024-02-05
Enrollment: 114
Sex: ALL
Minimum age (years): 14
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Despite significant advancements in the treatment of Crohn's disease (CD), approximately 50% of patients undergo surgical intervention within ten years of diagnosis. Furthermore, more than 70% of these patients experience endoscopic recurrence within one year after surgery. This subset of patients often faces a poorer long-term prognosis and requires long-term intensified medical therapy. Therefore, reducing early postoperative endoscopic recurrence has remained a crucial focus in CD research.

From a surgical perspective, there have been limited breakthroughs in improving surgical techniques to reduce the postoperative endoscopic recurrence rate in CD. Recent research indicates that microscopic inflammation at the cut edge of the CD bowel segment is a significant risk factor for postoperative endoscopic recurrence. Mesenteric wrapping is a unique clinical pathological feature of CD. Our retrospective data suggest a clear linear correlation between the degree of mesenteric wrapping and microscopic inflammation in the corresponding bowel segment. Surgical margins determined by mesenteric guidance significantly reduce the postoperative endoscopic recurrence rate and clinical relapse rate compared to the traditional 2 cm margin. However, there is currently no prospective study comparing the efficacy of these two surgical approaches.To address this, investigators plan to conduct a multicenter randomized controlled trial. This trial will focus on patients with ileocolonic CD who have undergone primary anastomosis without residual disease. investigators aim to compare the postoperative endoscopic recurrence rates between mesenteric-guided margins and the traditional 2 cm margins. Our goal is to determine whether mesenteric-guided margins can reduce the postoperative endoscopic recurrence rate and to conduct relevant mechanistic research. Ultimately, this research may lead to the development of a novel surgical approach for CD based on the findings of this study.

Detailed description: Current Status of the Study Current Status of the Study While treatment methods for Crohn's disease (CD) have made significant advancements, there is still a 50% requirement for surgical intervention within 10 years of diagnosis (1). The most common surgical procedures include ileocecal or terminal ileal resection. However, post-surgery, the risk of recurrence remains high, with 35% to 85% of patients experiencing endoscopic recurrence within one year (2, 4), and clinical recurrence occurring in 10% to 38% of patients within one year, leading to a need for reoperation in 30% of patients within five years (2, 3). Several studies have demonstrated that early endoscopic recurrence at six months post-surgery can effectively predict long-term treatment outcomes and guide subsequent medication choices (5).

Therefore, reducing early endoscopic anastomotic recurrence post-surgery has been a focus of CD research. The quality of surgical procedures significantly impacts this outcome. Previous research has identified risk factors for post-surgical recurrence, including smoking history, previous bowel resections, penetrating disease, extensive involvement, and concomitant perianal disease (6-8). However, these are non-modifiable patient-related factors. Within the scope of what physicians can control, proactive preventive treatment approaches adopted by gastroenterologists have been shown to reduce endoscopic recurrence rates to some extent. Nevertheless, the role and responsibilities of surgeons in this regard have not been clearly defined, and thus, there is a lack of standardized surgical strategies to reduce early endoscopic recurrence.（11） Intestinal mesentery abnormal proliferation and wrapping around the mesenteric margin is a characteristic pathological feature of Crohn's disease (CD). Recent studies have shown that mesenteric fat plays a crucial role in the development of CD (13, 14). The applicant's research team has also discovered the presence of bacteria displaced from the intestines within the mesentery, which can stimulate the proliferation of fat cells (15). Our preliminary retrospective data (pending submission) also suggests that if the mesenteric-guided margin, corresponding to the border of mesenteric abnormality, is used as the resection margin, even though an average of 10cm more intestine is removed, the postoperative endoscopic recurrence rate and clinical recurrence rate are significantly better than those of patients with the traditional limited 2cm margin (as described in the research foundation). However, there is currently no prospective randomized controlled study comparing these two margin strategies. Therefore, investigators plan to conduct a prospective multicenter randomized controlled study for patients with ileocolonic CD who undergo primary anastomosis without residual disease, comparing the postoperative endoscopic recurrence rates between mesenteric-guided margins and traditional 2cm margins, and conducting related mechanistic research to establish a high-level evidence for surgical margins that can reduce postoperative endoscopic recurrence in CD.

The significance of this research lies in addressing the issue of high endoscopic recurrence rates following surgery for Crohn's disease (CD), for which there is currently no established surgical solution. This study employs an innovative approach by using the mesenteric fat boundary as guidance for surgical resection margins, making it a novel contribution to both national and international research.

Building upon prior preliminary research, our research team aims to determine, through a prospective multicenter study, whether the use of mesentery-guided resection margins can reduce the endoscopic recurrence rate, while also exploring potential underlying mechanisms. The successful implementation of this project can provide high-level evidence for the correct selection of surgical margins in CD, fostering the development of personalized and precision surgical approaches in the treatment of CD in China, offering substantial clinical application and practical guidance.The ultimate goal of this study is to improve the long-term prognosis of CD patients and enhance their postoperative .

Eligibility criteria: Inclusion criteria:

1. Patients with a clear diagnosis of CD who meet the surgical indications and will undergo one-stage ileocecal resection.
2. Ileocecal CD with localized lesions involving the terminal ileum and cecum, with a total lesion length of \<60 cm.
3. Patients or their legal guardians who can understand and are willing to participate in this study, provide written informed consent, and have the ability to comply with the protocol.

Exclusion criteria:

1. Patients with a history of previous ileocecal resection.
2. Patients with primary lesions in other locations (e.g., proximal small bowel) that require surgical resection of inflamed intestinal segments other than the ileocecal region (excluding cases with affected other segments of the bowel).
3. Patients with a lesion length in the terminal ileum ≥60 cm.
4. Patients who only require ileal resection (excluding the ileocecal area), as this surgical procedure preserves the most distal ileum and the ileocecal valve.
5. Patients who require ileostomy formation.
6. Patients who have suffered from serious illnesses within the six months before surgery, such as myocardial infarction, active angina pectoris, congestive heart failure, or other diseases believed by the investigator to pose a risk to the patient's safety.
7. Patients with a history of malignant tumors, including melanoma (excluding localized skin cancer).
8. Patients clinically diagnosed with autoimmune diseases other than CD or with evidence of other autoimmune diseases.
9. Pregnant or lactating patients.
10. Patients who cannot be tracked at various study time points for the primary outcome measure.

Withdrawal criteria:

1. Subjects lost to follow-up or voluntarily requesting withdrawal.
2. The occurrence of anastomotic fistula after surgery that affects subsequent endoscopic evaluation.
3. Subjects considered unsuitable for further participation in the study by the investigator.

Primary outcomes:
measure: The Modified Rutgeerts Score during colonoscopy
timeFrame: At 6 months after surgery.
Secondary outcomes:
measure: To calculate the endoscopic recurrence rate for both groups within 1 year
timeFrame: At 1 year after surgery.
measure: Compare the clinical recurrence rates between the two groups
timeFrame: At 1 year after surgery.
measure: Calculate the rate of requiring a second surgery for both groups
timeFrame: At 3 years after surgery.
measure: Compare the postoperative margin pathology between the two surgical methods.
timeFrame: At 7 days after surgery
measure: Comparison of the length of bowel resection and intestinal function between the two surgical methods
timeFrame: At 7 days after surgery
measure: Comparison of the intestinal function of paticipants between the two surgical methods
timeFrame: At 3 years after surgery.
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Jia Ke
state: Guangdong
Study officials:
affiliation: Sixth Affiliated Hospital, Sun Yat-sen University
name: Jia Ke, M.D.
role: PRINCIPAL_INVESTIGATOR
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