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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Crohn Disease
• Intervention / Treatment: Drug: Azathioprine + infliximab; Procedure: Intestinal resection

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.

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Catherine Le Berre; Phone Number: + 33 (0)2 40 08 31 52; Email: catherine.leberre@chu-nantes.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Medical treatment; Combination therapy with subcutaneous infliximab and azathioprine	Drug: Azathioprine + infliximab; Combination therapy using 2-2.5 mg/kg oral azathioprine plus subcutaneous infliximab; Other Names: Imurel, Remsima
ACTIVE_COMPARATOR: Surgery; Intestinal resection	Procedure: Intestinal resection; Ileocolonic or small bowel resection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
inflammatory biomarkers (fecal calprotectin)	Mean values of fecal calprotectin	1, 6, 12, 18 and 24 months
inflammatory biomarkers ( C-reactive protein [CRP])	Mean values of CRP	1, 6, 12, 18 and 24 months
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
treatment failures	Proportion of patients without any treatment failures	12 and 24 months
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
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
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
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
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
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
Patient's acceptability -patients refusing to be included	Number of screened patients refusing to be included	24 months
patient's acceptability - The reason	The reason for refusing	24 months
intervention-related adverse events	Proportion of patients with intervention (drug or surgery) -related adverse events during the study	24 months
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

Collaborators and Investigators

• Sponsor: Nantes University Hospital
• Collaborators: Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): April 1, 2023
• Primary Completion (ANTICIPATED): October 1, 2027
• Study Completion (ANTICIPATED): October 1, 2027

Study Registration Dates

• First Submitted: September 26, 2022
• First Submitted That Met QC Criteria: October 14, 2022
• First Posted (ACTUAL): October 18, 2022

Study Record Updates

• Last Update Posted (ACTUAL): October 18, 2022
• Last Update Submitted That Met QC Criteria: October 14, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Crohn's disease; infliximab; resection; stricture; azathioprine
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Dermatologic Agents; Infliximab; Azathioprine
• Other Study ID Numbers: RC22_0408

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No