Active Surgical Intervention on Crohn's Disease

Effect of Active Surgical Intervention on Disease Remission in Patients With Crohn's Disease: A Single-Arm Trial

The study is to determine whether active surgical intervention promotes disease remission in patients with Crohn's Disease (CD).The management of CD involves both maintenance medication and medication used to control flares of the disease. The goal of maintenance therapy in CD is to maintain steroid- free remission, clinically and endoscopically. This requires regular clinical assessment including history, physical examination and at times colonoscopic examination. Other tools of assessment include blood (e.g. CRP, WCC) and stool (calprotectin) testing for inflammatory markers and imaging including MRI, CT or ultrasound.

The choice of maintenance treatment in CD is determined by disease extent, disease course (frequency of flares), failure of previous maintenance treatment, severity of the most recent flare, treatment used for inducing remission during the most recent flare, safety of maintenance treatment, and cancer prevention. The mainstay of maintenance medication are the 5-aminosalicylic acid compounds (5-ASA) such as mesalazine or sulphasalazine.

These compounds are commonly taken orally in formulations that predominantly deliver the active 5-ASA component to the colon. Alternatively, or in addition, mesalazine preparations can be delivered topically via enema or suppository if the disease only involves the left side of the colon (although it is only PBS funded for topical therapy during a flare and not for maintenance of remission - even though it also works in this setting). The majority of patients can be managed with maintenance 5-ASA compounds most of the time. For patients who have repeated flares of disease on 5-ASA maintenance therapy (1 or more flares in a year needing steroids), thiopurine medication such as azathioprine or 6-mercapropurine should be used. These medications induce systemic immunosuppression, reduce the incidence and severity of flares of colitis but also slightly increase the risk of some infections and malignancy. Anti TNF agents such as infliximab or adalimumab have been shown to have benefit in maintaining remission in CD (and are licensed for this indication by the TGA), however these agents are very expensive and not funded by the pharmaceutical benefits scheme in Australia and so, are not readily available. The anti TNF agents also give an increased risk of infection, particularly latent TB reactivation.

Mild flares of CD can be managed with higher doses of oral 5-ASA compounds or the addition of topical 5-ASAs given via enema or suppository. More severe flares are usually managed with a course of systemic corticosteroid. These can be given intravenously in acute, severe disease or orally in less severe flares. The steroids should then be tapered over time and discontinued. There is no indication for long term steroid use in CD and prolonged steroid use is associated with a number of complications including infection, osteoporosis, obesity, diabetes, poor wound healing, thinning skin, mood changes and insomnia. Severe flares of CD not responsive to steroids may respond to rescue therapy with the addition of either cyclosporin or anti-TNF therapy.

Patients in whom colonic inflammation cannot be controlled adequately frequently undergo total colectomy. This may be done electively (for refractory disease) or emergently in acute fulminant colitis. Colectomy entails surgical risk that is higher in the emergent setting; this risk includes infection, wound breakdown and a mortality rate. Colectomy is considered "curative" for CD especially if they have an ileostomy stoma created, however, it frequently also leads to complications both short- and long-term. In addition, in patients in whom an ileal-anal pouch is fashioned up to 50% will subsequently develop pouchitis at 4 years post surgery.

Patient eligibility was determined during a 5-week screening period, during which time details on patient demographics, medical history, and previous and concomitant medications were obtained,and the following assessments were completed: viral serology, stool culture, Crohn's Disease Activity Index (CDAI) patient diary and clinical score, Simple Endoscopic Score for Crohn's Disease (SES-CD), colonoscopy and colonic biopsy, stool collection for faecal biomarkers, vital signs, and laboratory evaluations.

All participants need to be subjected to rigorous assessments mentioned above at week 4, week 8 and week 12 after receiving active surgical intervention (two kinds: one is colostomy, and the other one is colonic exclusion).

Study Overview

• Status: Not yet recruiting
• Conditions: Crohn Disease
• Intervention / Treatment: Procedure: active surgical intervention

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Wei Shen, PhD, MD; Phone Number: +86 133 5811 0723; Email: shenweijs@outlook.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Moderate to severe active CD (CDAI ≥ 150)
2. Endoscopic subscore meet the criteria (SES-CD ≥ 4)
3. Patients aged 18 to 75 years with established diagnosis of CD

Exclusion Criteria:

1. Mild active CD (CDAI < 150)
2. More than 25mg of prednisolone per day (or equivalent steroid)
3. Previous colonic surgery
4. Active gastrointestinal infection
5. Pregnancy
6. Anticoagulant therapy or duel antiplatelet therapy (i.e. aspirin and clopidogrel)
7. Current use of antibiotics
8. Anti-TNF therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: active enterostomy; active enterostomy before serious complications	Procedure: active surgical intervention; two kinds: one is colostomy, and the other one is colonic exclusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SES-CD	Simple Endoscopic Score for Crohn's Disease	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CDAI	Crohn's Disease Activity Index	12 weeks

Collaborators and Investigators

• Sponsor: Wuxi People's Hospital
• Investigators: Study Chair: Peihua Lu, PhD, MD, The Affiliated Wuxi People's Hospital of Nanjing Medical University

Study record dates

Study Major Dates

• Study Start (Anticipated): September 16, 2022
• Primary Completion (Anticipated): March 16, 2024
• Study Completion (Anticipated): May 16, 2024

Study Registration Dates

• First Submitted: August 25, 2022
• First Submitted That Met QC Criteria: August 28, 2022
• First Posted (Actual): August 31, 2022

Study Record Updates

• Last Update Posted (Actual): August 31, 2022
• Last Update Submitted That Met QC Criteria: August 28, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: WXSW-CD-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: To determine whether active surgical intervention promotes disease remission in patients with Crohn's Disease (CD).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No