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

N/ANot Yet RecruitingNCT05584228

Nantes University Hospital150 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

150

Conditions

Crohn Disease

Interventions

Azathioprine + infliximabDRUG

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

Intestinal resectionPROCEDURE

Ileocolonic or small bowel resection

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

IBD (inflammatory bowel disease) - related quality of life

Mean total inflammatory bowel disease questionnaire (IBDQ - Inflammatory Bowel Disease Questionnaire ) score. The total score ranges from 32 to 224, the higher the score the better the quality of life.

Time frame: 12 months

Secondary Outcomes

IBD (inflammatory bowel disease) -related quality of life

Time frame: 1, 3, 6, 9, 18 and 24 months

Endoscopic remission

Proportion of patients achieving endoscopic remission at month 6 (SES-CD \< 2 in case of medical treatment or Rutgeerts score \< i,2 in case of resection)

Time frame: 6 months

Obstructive symptoms

Mean total score of CDOS (CROHN'S DISEASE OBSTRUCTIVE SCORE ) Scale frome 0 to 6. 0 is the best outcome.

Time frame: 1, 3, 6, 9, 12, 18 and 24 months

Clinical activity

Mean total score of CDAI (CROHN'S DISEASE ACTIVITY INDEX ) Scale from 0 to 1100. 0 is the best outcome.

Time frame: 1, 3, 6, 9, 12, 18 and 24 months

inflammatory biomarkers (fecal calprotectin)

Mean values of fecal calprotectin

Time frame: 1, 6, 12, 18 and 24 months

inflammatory biomarkers ( C-reactive protein [CRP])

Mean values of CRP

Central Contacts

Catherine Le Berre

CONTACT

(0)2 40 08 31 52 catherine.leberre@chu-nantes.fr

Data from ClinicalTrials.gov

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