Crohn Disease
Conditions
Keywords
Crohn's disease, stricture, resection, infliximab, azathioprine
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.
Interventions
DRUGAzathioprine + infliximab
Combination therapy using 2-2.5 mg/kg oral azathioprine plus subcutaneous infliximab
PROCEDUREIntestinal resection
Ileocolonic or small bowel resection
Sponsors
Nantes University Hospital
Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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) |
| 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. |
| 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. |
| inflammatory biomarkers (fecal calprotectin) | 1, 6, 12, 18 and 24 months | Mean values of fecal calprotectin |
| inflammatory biomarkers ( C-reactive protein [CRP]) | 1, 6, 12, 18 and 24 months | Mean values of CRP |
| 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 |
| treatment failures | 12 and 24 months | Proportion of patients without any treatment failures |
| 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) |
| 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. |
| 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 |
| 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 |
| 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 |
| 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. |
| Patient's acceptability -patients refusing to be included | 24 months | Number of screened patients refusing to be included |
| patient's acceptability - The reason | 24 months | The reason for refusing |
| intervention-related adverse events | 24 months | Proportion of patients with intervention (drug or surgery) -related adverse events during the study |
| 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 |
Countries
France
Contacts
CONTACTCatherine Le Berre
Outcome results
None listed