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

Sponsor
Nantes University Hospital (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05584228
Collaborator
Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives (Other)
150
2
54

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Azathioprine + infliximab
  • Procedure: Intestinal resection
N/A

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 Design

Study Type:
Interventional
Anticipated Enrollment :
150 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
SyMptomAtic Stricturing Small Bowel CRohn's Disease - Medical Treatment Versus Surgery, a Prospective, Multi-centre, Randomized, Non-inferiority Trial
Anticipated Study Start Date :
Apr 1, 2023
Anticipated Primary Completion Date :
Oct 1, 2027
Anticipated Study Completion Date :
Oct 1, 2027

Arms and Interventions

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

    Outcome Measures

    Primary Outcome Measures

    1. IBD (inflammatory bowel disease) - related quality of life [12 months]

      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.

    Secondary Outcome Measures

    1. IBD (inflammatory bowel disease) -related quality of life [1, 3, 6, 9, 18 and 24 months]

      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.

    2. Endoscopic remission [6 months]

      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)

    3. Obstructive symptoms [1, 3, 6, 9, 12, 18 and 24 months]

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

    4. Clinical activity [1, 3, 6, 9, 12, 18 and 24 months]

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

    5. inflammatory biomarkers (fecal calprotectin) [1, 6, 12, 18 and 24 months]

      Mean values of fecal calprotectin

    6. inflammatory biomarkers ( C-reactive protein [CRP]) [1, 6, 12, 18 and 24 months]

      Mean values of CRP

    7. imaging parameters [12 months]

      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

    8. treatment failures [12 and 24 months]

      Proportion of patients without any treatment failures

    9. patient-reported outcomes (disability) [1, 3, 6, 9, 12, 18 and 24 months]

      Mean total score of IBD-DI (INFLAMMATORY BOWEL DISEASE DISABILITY INDEX ) Score from 0 to 100. 0 is the best outcome (no disability)

    10. patient-reported outcomes (work productivity) [1, 3, 6, 9, 12, 18 and 24 months]

      Mean total score of WPAI (WORK PRODUCTIVITY AND ACTIVITY IMPAIRMENT QUESTIONNAIRE) In percentage from 0 to 100.

    11. patient-reported outcomes (fatigue) [1, 3, 6, 9, 12, 18 and 24 months]

      Mean total score of FACIT-F (Functional Assessment of Chronic Illness Therapy ) scores from 0 to 52, with higher scores corresponding to less fatigue

    12. patient-reported outcomes (body image) [1, 3, 6, 9, 12, 18 and 24 months]

      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

    13. patient-reported outcomes (generic quality-of-life) [1, 3, 6, 9, 12, 18 and 24 months]

      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

    14. patient-reported outcomes (anxiety/depression) [1, 3, 6, 9, 12, 18 and 24 months]

      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.

    15. Patient's acceptability -patients refusing to be included [24 months]

      Number of screened patients refusing to be included

    16. patient's acceptability - The reason [24 months]

      The reason for refusing

    17. intervention-related adverse events [24 months]

      Proportion of patients with intervention (drug or surgery) -related adverse events during the study

    18. efficiency of medical treatment compared to surgery as assessed by a cost-utility analysis performed from a collective perspective [24 months]

      Incremental cost-utility ratio (cost per Quality-Adjusted Life-Years, QALYs) from a collective perspective

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

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

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Nantes University Hospital
    ClinicalTrials.gov Identifier:
    NCT05584228
    Other Study ID Numbers:
    • RC22_0408
    First Posted:
    Oct 18, 2022
    Last Update Posted:
    Oct 18, 2022
    Last Verified:
    Sep 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Nantes University Hospital
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Oct 18, 2022