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

Nantes University Hospital (NUH)

Status: Not yet enrolling

Conditions: Crohn Disease

Treatments: Procedure: Intestinal resection; Drug: Azathioprine + infliximab

Study type: Interventional

Funder types: Other

Identifiers

NCT05584228

RC22_0408

Details and patient eligibility

About

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.

Full 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.

Enrollment: 150 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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150 participants in 2 patient groups

Medical treatment

Experimental group

Description:

Combination therapy with subcutaneous infliximab and azathioprine

Treatment:

Drug: Azathioprine + infliximab

Surgery

Active Comparator group

Description:

Intestinal resection

Treatment:

Procedure: Intestinal resection