Clinical trial NCT05584228: Medical Treatment Versus Surgery in Stricturing Small Bowel Crohn's Disease
Official title: SyMptomAtic Stricturing Small Bowel CRohn's Disease - Medical Treatment Versus Surgery, a Prospective, Multi-centre, Randomized, Non-inferiority Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Crohn Disease
Keywords: Crohn's disease
stricture
resection
infliximab
azathioprine
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
Collaborators: name: Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives
First posted: 2022-10-18
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: IBD (inflammatory bowel disease) - related quality of life
timeFrame: 12 months
Secondary outcomes:
measure: IBD (inflammatory bowel disease) -related quality of life
timeFrame: 1, 3, 6, 9, 18 and 24 months
measure: Endoscopic remission
timeFrame: 6 months
measure: Obstructive symptoms
timeFrame: 1, 3, 6, 9, 12, 18 and 24 months
measure: Clinical activity
timeFrame: 1, 3, 6, 9, 12, 18 and 24 months
measure: inflammatory biomarkers (fecal calprotectin)
timeFrame: 1, 6, 12, 18 and 24 months
measure: inflammatory biomarkers ( C-reactive protein [CRP])
timeFrame: 1, 6, 12, 18 and 24 months
measure: imaging parameters
timeFrame: 12 months
measure: treatment failures
timeFrame: 12 and 24 months
measure: patient-reported outcomes (disability)
timeFrame: 1, 3, 6, 9, 12, 18 and 24 months
measure: patient-reported outcomes (work productivity)
timeFrame: 1, 3, 6, 9, 12, 18 and 24 months
measure: patient-reported outcomes (fatigue)
timeFrame: 1, 3, 6, 9, 12, 18 and 24 months
measure: patient-reported outcomes (body image)
timeFrame: 1, 3, 6, 9, 12, 18 and 24 months
measure: patient-reported outcomes (generic quality-of-life)
timeFrame: 1, 3, 6, 9, 12, 18 and 24 months
measure: patient-reported outcomes (anxiety/depression)
timeFrame: 1, 3, 6, 9, 12, 18 and 24 months
measure: Patient's acceptability -patients refusing to be included
timeFrame: 24 months
measure: patient's acceptability - The reason
timeFrame: 24 months
measure: intervention-related adverse events
timeFrame: 24 months
measure: efficiency of medical treatment compared to surgery as assessed by a cost-utility analysis performed from a collective perspective
timeFrame: 24 months
Other outcomes:
Locations:
Study officials:
References: