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

Crohn Disease Clinical Trial

— SMART  

Official title:

SyMptomAtic Stricturing Small Bowel CRohn's Disease - Medical Treatment Versus Surgery, a Prospective, Multi-centre, Randomized, Non-inferiority Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05584228
• Other study ID #: RC22_0408
• Status: Not yet recruiting
• Phase: N/A
• Start date: April 1, 2023
• Est. completion date: October 1, 2027

Study information

• Verified date: September 2022
• Source: Nantes University Hospital
• Contact: Catherine Le Berre
• Phone: (0)2 40 08 31 52
• Email: catherine.leberre[@]chu-nantes.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 150
• Est. completion date: October 1, 2027
• Est. primary completion date: October 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Crohn Disease

Intervention

Drug:
• Azathioprine + infliximab
Combination therapy using 2-2.5 mg/kg oral azathioprine plus subcutaneous infliximab

Procedure:
• Intestinal resection
Ileocolonic or small bowel resection

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Nantes University Hospital	Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	12 months
Secondary	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.	1, 3, 6, 9, 18 and 24 months
Secondary	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)	6 months
Secondary	Obstructive symptoms	Mean total score of CDOS (CROHN'S DISEASE OBSTRUCTIVE SCORE ) Scale frome 0 to 6. 0 is the best outcome.	1, 3, 6, 9, 12, 18 and 24 months
Secondary	Clinical activity	Mean total score of CDAI (CROHN'S DISEASE ACTIVITY INDEX ) Scale from 0 to 1100. 0 is the best outcome.	1, 3, 6, 9, 12, 18 and 24 months
Secondary	inflammatory biomarkers (fecal calprotectin)	Mean values of fecal calprotectin	1, 6, 12, 18 and 24 months
Secondary	inflammatory biomarkers ( C-reactive protein [CRP])	Mean values of CRP	1, 6, 12, 18 and 24 months
Secondary	imaging parameters	Proportion of patients with an improvement in wall thickening, contrast enhancement, T2-signal increase, diffusion weighted-signal increase and length of pathological segment at month 12 as compared to screening imaging (MRI) by physician global assessment	12 months
Secondary	treatment failures	Proportion of patients without any treatment failures	12 and 24 months
Secondary	patient-reported outcomes (disability)	Mean total score of IBD-DI (INFLAMMATORY BOWEL DISEASE DISABILITY INDEX ) Score from 0 to 100. 0 is the best outcome (no disability)	1, 3, 6, 9, 12, 18 and 24 months
Secondary	patient-reported outcomes (work productivity)	Mean total score of WPAI (WORK PRODUCTIVITY AND ACTIVITY IMPAIRMENT QUESTIONNAIRE) In percentage from 0 to 100.	1, 3, 6, 9, 12, 18 and 24 months
Secondary	patient-reported outcomes (fatigue)	Mean total score of FACIT-F (Functional Assessment of Chronic Illness Therapy ) scores from 0 to 52, with higher scores corresponding to less fatigue	1, 3, 6, 9, 12, 18 and 24 months
Secondary	patient-reported outcomes (body image)	Mean total score of body image questionnaire Ranges from 0 to 30 and can be calculated by summing up the 10 items. A higher score means a higher level of body image disturbance	1, 3, 6, 9, 12, 18 and 24 months
Secondary	patient-reported outcomes (generic quality-of-life)	Mean total score of SF-36 (QUESTIONNAIRE SHORT FORM 36 HEALTH SURVEY ) Score ranging from 0 to 100. A low score reflects a perception of poor health, loss of function, presence of pain. A high score reflects a perception of good health, absence of functional deficit and pain	1, 3, 6, 9, 12, 18 and 24 months
Secondary	patient-reported outcomes (anxiety/depression)	Mean total score of HAD (Hospital Anxiety and Depression scale) 14 items rated from 0 to 3. Seven questions relate to anxiety (total A) and seven others to the depressive dimension (total D), thus allowing two scores (maximum score for each score = 21). Minimum : 0. The best outcome is 0.	1, 3, 6, 9, 12, 18 and 24 months
Secondary	Patient's acceptability -patients refusing to be included	Number of screened patients refusing to be included	24 months
Secondary	patient's acceptability - The reason	The reason for refusing	24 months
Secondary	intervention-related adverse events	Proportion of patients with intervention (drug or surgery) -related adverse events during the study	24 months
Secondary	efficiency of medical treatment compared to surgery as assessed by a cost-utility analysis performed from a collective perspective	Incremental cost-utility ratio (cost per Quality-Adjusted Life-Years, QALYs) from a collective perspective	24 months