Medical Treatment Versus Surgery in Stricturing Small Bowel Crohn's Disease

NCT ID: NCT05584228

Last Updated: 2022-10-18

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-01
• Study Completion Date: 2027-10-01

Brief Summary

The objective of the SMART trial is to compare a combination therapy using azathioprine and subcutaneous infliximab versus ileocecal resection in patients with symptomatic small bowel Crohn's disease.

Detailed Description

Crohn's disease (CD) is a chronic, disabling and destructive inflammatory bowel disease (IBD) leading to progressive and cumulative bowel damage, including fistulas and strictures. Strictures are defined as intestinal luminal narrowing and can lead to obstructive symptoms in the medium-to-long term. Symptomatic strictures significantly impair patient's quality of life by the presence of obstructive symptoms such as abdominal pain, nausea, vomiting, abdominal distension, and dietary restrictions leading to malnutrition. Strictures can appear anywhere in the gastrointestinal tract, but affect most commonly the terminal ileum. Epidemiological studies indicate that more than 40% of patients with ileal CD will develop strictures.

However, treatment strategies are not well-defined in this indication. Most patients undergo surgery but recent observations indicate that a medical treatment by anti-TNF may be considered in stricturing CD. The European Crohn's Colitis Organization recommends that "ileocecal CD with obstructive symptoms, but no significant evidence of active inflammation, should be treated by surgery". However, the lack of inflammation is difficult to demonstrate and does not predict the extent of fibrosis, and inflammation and fibrosis are often associated. Thus, there is a need for better defining therapeutic strategies.

The objective of the SMART trial is to compare for the first time medical versus surgical approaches in stricturing CD. Indeed, up to date, no randomized controlled trial has been conducted to compare medical treatment alone versus surgery in patients with symptomatic stricturing CD. The hypothesis is that medical treatment by a combination therapy using infliximab and azathioprine is non-inferior to surgical resection in terms of health-related quality of life (HRQoL) at 1 year, with the advantage of being conservative as regards the high rates of post-operative recurrence with the subsequent risk of small bowel syndrome, as well as highly more acceptable by patients, especially since infliximab is now available as a biosimilar in a subcutaneous formulation, which should also improve the cost-effectiveness of the medical strategy.

Conditions

Crohn Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Medical treatment

Combination therapy with subcutaneous infliximab and azathioprine

Group Type: EXPERIMENTAL

Azathioprine + infliximab

Intervention Type: DRUG

Combination therapy using 2-2.5 mg/kg oral azathioprine plus subcutaneous infliximab

Surgery

Intestinal resection

Group Type: ACTIVE_COMPARATOR

Intestinal resection

Intervention Type: PROCEDURE

Ileocolonic or small bowel resection

Interventions

Azathioprine + infliximab

Combination therapy using 2-2.5 mg/kg oral azathioprine plus subcutaneous infliximab

Intervention Type: DRUG

Intestinal resection

Ileocolonic or small bowel resection

Intervention Type: PROCEDURE

Other Intervention Names

Imurel, Remsima

Eligibility Criteria

Inclusion Criteria

• Age between 18 and 70 years
• Male or female
• Documented small bowel CD with intestinal stricture(s) identified on CT, MRI or endoscopy, AND responsible for obstructive symptoms
• CREOLE score > 2

Exclusion Criteria

• Adults under guardianship, safeguard justice or trusteeship
• Pregnant or breastfeeding female
• Acute bowel obstruction requiring urgent surgical intervention
• Suspected or confirmed gastrointestinal perforation
• Concurrent active perianal sepsis
• Internal fistulizing disease in association with strictures
• Colonic stenosis and/or colonic active disease at screening endoscopy
• Contra-indication to surgery, general anesthesia, anti-TNF, thiopurines
• Use of corticosteroids (prednisolone > 20 mg daily or equivalent) within 4 weeks prior to visit V0
• Treatment with any biologics within 8 weeks before visit V0
• Presence of a stoma
• HIV/HCV/HBV infection

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives

OTHER

Sponsor Role: collaborator

Nantes University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Central Contacts

Catherine Le Berre

Role: CONTACT

catherine.leberre@chu-nantes.fr

(0)2 40 08 31 52 ext. + 33

Other Identifiers

RC22_0408

Identifier Type: -

Identifier Source: org_study_id