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Prevention of Postoperative Endoscopic Recurrence With Endoscopy-driven Versus Systematic Biological Therapy (SOPRANO-CD)

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ClinicalTrials.gov Identifier: NCT05169593
Recruitment Status : Recruiting
First Posted : December 27, 2021
Last Update Posted : March 17, 2023
Sponsor:
Information provided by (Responsible Party):
Universitaire Ziekenhuizen KU Leuven

Study Description
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Brief Summary:

With this prospective, randomized, multicentre, parallel group pragmatic non-inferiority trial, the investigators will evaluate if endoscopy-driven introduction of biological therapy is not leading to more postoperative endoscopic recurrence at week 86 compared to systematic prophylactic biological therapy in patients with CD undergoing an ileocolonic resection with ileocolonic anastomosis. Secondary analyses will include influence on clinical, biological and surgical CD recurrence, serious adverse events, direct costs, work productivity, and quality of life. If the investigators can demonstrate the non-inferiority of an endoscopy-driven approach, this patient-tailored management could be advocated, while a more expensive systematic introduction of biological therapies could be limited.

Finally, endoscopic images provided through the SOPRANO CD study, will be used to develop a new scoring system evaluating postoperative endoscopic recurrence.


Condition or disease Intervention/treatment Phase
Crohn Disease Drug: Biological Drug Phase 4

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Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 292 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: A randomized, multicentre, parallel group pragmatic non-inferiority trial
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Prevention of Postoperative Endoscopic Recurrence With Endoscopy-driven Versus Systematic Biological Therapy: a Randomized, Multicentre, Parallel Group Pragmatic Non-inferiority Trial in Crohn Disease
Actual Study Start Date : September 8, 2022
Estimated Primary Completion Date : October 2027
Estimated Study Completion Date : October 2030

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Endoscopy-driven postoperative biological therapy

Endoscopic recurrence at week 30

Adalimumab: 160 mg SC at week 32, 80 mg SC at week 34, 40 mg SC at week 36 and every two weeks thereafter.

Infliximab: Induction with 5 mg/kg IV at week 32, and 5 mg/kg IV at week 34; maintenance with 5 mg/kg IV at week 38, week 42 or week 46 and every eight weeks thereafter or with 120 mg SC at week 38 and every two weeks thereafter.

Ustekinumab: 260 mg (body weight ≤55kg) or 390 mg (55-85kg) or 520 mg (>85kg) IV at week 32, 90 mg SC at week 40, and every eight weeks thereafter.

Vedolizumab: Induction with 300 mg IV at week 32, and 300 mg IV at week 34; maintenance with 300 mg IV at week 38 and every eight weeks thereafter or with 108 mg SC at week 38, week 42 or week 46 and every two weeks thereafter.

Risankizumab: Induction with 600 mg IV at week 32, week 36 and week 40; maintenance with 360 mg SC at week 44 and every eight weeks thereafter.

 Drug: Biological Drug
Biological therapy used in daily clinical practice in patients with Crohn's disease to prevent disease recurrence
Other Names:
  • Risankizumab
  • Vedolizumab
  • Ustekinumab
  • Infliximab
  • Adalimumab
Active Comparator: Systematic postoperative prophylaxis with a biological

Adalimumab: 160 mg subcutaneous (SC) at day 0, 80 mg SC at week 2, 40 mg SC at week 4 and every two weeks thereafter.

Infliximab: Induction with 5 mg/kg intravenous (IV) at day 0, and 5 mg/kg IV at week 2; maintenance with 5 mg/kg IV at week 6, week 10 or week 14 and every eight weeks thereafter or with 120 mg SC at week 6 and every two weeks thereafter.

Ustekinumab: 260 mg (body weight ≤55kg), 390 mg (55-85kg) or 520 mg (>85kg) IV at day 0, 90 mg SC at week 8 and every eight weeks thereafter.

Vedolizumab: Induction with 300 mg IV at day 0, and 300 mg IV at week 2; maintenance with 300 mg IV at week 6 and every eight weeks thereafter or with 108 mg SC at week 6, week 10 or week 14 and every two weeks thereafter.

Risankizumab: Induction with 600 mg IV at day 0, week 4 and week 8; maintenance with 360 mg SC at week 12 and every eight weeks thereafter.

 Drug: Biological Drug
Biological therapy used in daily clinical practice in patients with Crohn's disease to prevent disease recurrence
Other Names:
  • Risankizumab
  • Vedolizumab
  • Ustekinumab
  • Infliximab
  • Adalimumab


Outcome Measures
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Primary Outcome Measures :
  1. postoperative endoscopic recurrence (Rutgeerts score ≥i2b) [ Time Frame: 86 weeks ]
    To compare the postoperative endoscopic recurrence rate in patients with Crohn's disease undergoing an ileocolonic resection with ileocolonic anastomosis randomized to systematic biological therapy or endoscopy-driven biological therapy

  2. need for unscheduled treatment adaptation prior to week 86 [ Time Frame: 86 weeks ]
    When, due to clinical symptoms, therapy needs to be started or switched prior to week 86


Secondary Outcome Measures :
  1. Harvey Bradshaw Index (HBI) based clinical recurrence [ Time Frame: 86 weeks ]
    HBI based clinical recurrence (score higher than 4) prior to week 86. HBI based clinical recurrence is defined as HBI >4; AND objective signs of disease recurrence, namely faecal calprotectin >250 µg/g, CRP >5 mg/L, or endoscopic recurrence Rutgeerts score ≥i2b, or clear radiological disease activity at the neo-terminal ileum.

  2. Direct costs [ Time Frame: 86 weeks ]
    Direct costs from Baseline to week 86

  3. new ileocolonic resection [ Time Frame: 86 weeks ]
    Need for a new ileocolonic resection prior to week 86

  4. Severe adverse reactions [ Time Frame: 86 weeks ]
    Severe adverse reactions to biological therapy prior to week 86

  5. Serious adverse events [ Time Frame: 86 weeks ]
    Serious adverse events prior to week 86

  6. European Quality of Live Five Dimension Five Level Scale [ Time Frame: 86 weeks ]
    Quality of life at week 30, week 62 and week 86 in comparison to Baseline (score between 0 and 100; higher score, better quality of life)


Other Outcome Measures:
  1. Crohn's disease activity index (CDAI) based clinical recurrence [ Time Frame: 86 weeks ]
    CDAI based clinical recurrence prior and at week 86 and time to CDAI based clinical recurrence

  2. Harvey Bradshaw Index (HBI score higher than 4) based clinical recurrence [ Time Frame: 86 weeks ]
    HBI based clinical recurrence at week 86 and time to HBI based clinical recurrence. HBI based clinical recurrence is defined as HBI >4; AND objective signs of disease recurrence, namely faecal calprotectin >250 µg/g, CRP >5 mg/L, or endoscopic recurrence ≥i2b, or clear radiological disease activity at the neo-terminal ileum.

  3. Two-component Patient Reported Outcome (PRO-2) based clinical recurrence [ Time Frame: 86 weeks ]
    PRO-2 based clinical recurrence prior and at week 86 and time to PRO-2 clinical recurrence. PRO-2 based clinical recurrence is defined as average liquid or very soft stool frequency of >2.8 and/or abdominal pain score >1.0

  4. Endoscopic disease activity [ Time Frame: 86 weeks ]
    Endoscopic disease activity (Rutgeerts score ≥i3, ≥i2a, or ≥i1) at week 86

  5. Endoscopic recurrence [ Time Frame: 30 weeks ]
    Endoscopic recurrence (Rutgeerts score ≥i2b) at week 30

  6. Endoscopic disease activity [ Time Frame: 30 weeks ]
    Endoscopic disease activity (Rutgeerts score ≥i3, ≥i2a, or ≥i1) at week 30

  7. Persistent endoscopic recurrence [ Time Frame: 86 weeks ]
    Persistent endoscopic recurrence at week 86 after development of endoscopic recurrence at week 30

  8. a new ileocolonic resection, a balloon dilation or a strictureplasty [ Time Frame: 86 weeks ]
    Need for a new ileocolonic resection, a balloon dilation or a strictureplasty at the site of the ileocolonic anastomosis prior to week 86

  9. Work Productivity and Activity Impairment in Crohn's Disease questionnaire [ Time Frame: 86 weeks ]
    Work productivity and activity impairment at week 30, week 62 and week 86 in comparison to Baseline (score between 0 and 20; lower score, better outcome)

  10. Change in medical therapy [ Time Frame: 86 weeks ]
    Change in medical therapy for Crohn's disease prior to week 86

  11. Change in C-reactive protein [ Time Frame: 86 weeks ]
    Change CRP at week 14, week 30, week 46, week 62 and week 86 in comparison to baseline

  12. Change in faecal calprotectin [ Time Frame: 86 weeks ]
    Change in faecal calprotectin at week 14, week 30, week 46, week 62 and week 86 in comparison to baseline

  13. unscheduled visits [ Time Frame: 86 weeks ]
    Number of unscheduled visits related to CD (clinical visit, endoscopic or radiological evaluation)

  14. Suspected unexpected serious adverse reactions [ Time Frame: 86 weeks ]
    Suspected unexpected serious adverse reactions prior to week 86

  15. Two-component Patient Reported Outcome (PRO-2) based clinical recurrence in longterm follow-up [ Time Frame: 242 weeks ]
    Evolution of PRO-2 at week 138, 190 and 242 in comparison to Baseline and Week 86

  16. European Quality of Live Five Dimension Five Level Scale in longterm follow-up [ Time Frame: 242 weeks ]
    Evolution of EQ-5D 5L at week 138, 190 and 242 in comparison to Baseline and Week 86

  17. Work Productivity and Activity Impairment in Crohn's Disease questionnaire in longterm follow-up [ Time Frame: 242 weeks ]
    Evolution of WPAI:CD at week 138, 190 and 242 in comparison to Baseline and Week 86

  18. Change in C-reactive protein in longterm follow-up [ Time Frame: 242 weeks ]
    Evolution of CRP at week 138, 190 and 242 in comparison to Baseline and Week 86

  19. Change in faecal calprotectin in longterm follow-up [ Time Frame: 242 weeks ]
    Evolution of faecal calprotectin at week 138, 190 and 242 in comparison to Baseline and Week 86

  20. Change in medical therapy in longterm follow-up [ Time Frame: 242 weeks ]
    Change in medical therapy for Crohn's disease prior to week 138, 190 and 242

  21. a new ileocolonic resection, a balloon dilation or a strictureplasty in longterm follow-up [ Time Frame: 242 weeks ]
    Need for a new ileocolonic resection, a balloon dilation or a strictureplasty at the site of the ileocolonic anastomosis prior to week 138, 190 and 242

  22. Severe adverse reactions in longterm follow-up [ Time Frame: 242 weeks ]
    Severe adverse reactions to biological therapy prior to week 138, 190 and 242

  23. Serious adverse events in longterm follow-up [ Time Frame: 242 weeks ]
    Serious adverse events prior to week 138, 190 and 242

  24. Suspected unexpected serious adverse reactions in longterm follow-up [ Time Frame: 242 weeks ]
    Suspected unexpected serious adverse reactions prior to week 138, 190 and 242


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures.
  2. Patients with a diagnosis of Crohn's disease based on radiology, endoscopy and/or histology
  3. Males and females 18-80 years old.

  4. Patients undergoing an ileocolonic resection with ileocolonic anastomosis (with or without temporary ileostomy) within 3 and 40 days prior to the Screening visit.

    Patients who underwent an ileocolonic resection with ileocolonic anastomosis with a temporary ileostomy are also eligible if the ileocolonic resection was performed within eight months prior to the Screening visit, and the restoration of the faecal stream was performed within 3 and 40 days prior to the Screening visit.

  5. Patients having an increased risk for postoperative recurrence for any of the following reasons:

    1. Penetrating disease as reason for ileocolonic resection
    2. Previous ileocolonic resection within ten years of index surgery
    3. Two or more previous ileocolonic resections
    4. Active smoking
    5. Biological therapy for Crohn's disease within 3 months of index ileocolonic resection
  6. Curative ileocolonic resection. All inflamed colon segments should have been removed. Strictureplasties in the small bowel not involving the anastomotic region are allowed.
  7. Patients previously failing at least three months of steroids and/or three months of immunosuppressive therapy, or showing intolerance or a real contraindication for any of these therapies.
  8. Patients able and willing to start and continue biological therapy, and this at the timepoint indicated through study randomization

Exclusion Criteria:

  1. Participant has a history of primary non response or secondary loss of response to all five biological therapies of interest, namely adalimumab, infliximab, ustekinumab, vedolizumab and risankizumab..
  2. Any disorder, which in the Investigator's opinion might jeopardise the participant's safety or compliance with the protocol.
  3. Any prior or concomitant treatment(s) that might jeopardise the participant's safety or that would compromise the integrity of the Trial.
  4. Participation in an interventional Trial with an Investigational Medicinal Product (IMP) or device.
  5. Patients initiating biological therapy for CD as part of another clinical trial or a medical need program.
  6. Patients not understanding Dutch, French, German or English.
  7. Patients with ulcerative colitis or inflammatory bowel disease type unclassified.
  8. Patients with an ileorectal anastomosis, or an ileal pouch-anal anastomosis.
  9. Patients with active perianal disease.
  10. Patients with a colorectal stenosis.
  11. Patients with an ostomy.
  12. Patients with sepsis or other postoperative complications necessitating the use of antibiotics for more than ten days after ileocolonic resection or restoration of the faecal stream.
  13. Patients with (an imminent risk) of a short bowel syndrome.
  14. Patients who had qualifying ileocolonic resection for dysplasia or cancer without ongoing inflammation.
  15. Patients with liver test abnormalities (aspartate transaminase, alanine transaminase, alkaline phosphatases, or bilirubin > 2 upper limit of normal), leukopenia (<3000 white blood cells 109/L, <1500 neutrophils 109/L ), thrombocytopenia (platelets < 50.000/mm3).
  16. Patients with severe renal, pulmonary or cardiac disease.
  17. Ongoing alcohol or substance abuse.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05169593


Contacts
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Contact: Marc Ferrante, Professor 016 342845 ext +32 marc.ferrante@uzleuven.be
Contact: Dorien Beeckmans, PhD 016 348545 ext +32 dorien.beeckmans@uzleuven.be

Locations
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Sponsors and Collaborators
Universitaire Ziekenhuizen KU Leuven
Investigators
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Principal Investigator: Marc Ferrante, Professor IG/MAAG-DARM-LEVER, UZ Leuven, campus Gasthuisberg, Herestraat 49 3000 Leuven
More Information
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Responsible Party: Universitaire Ziekenhuizen KU Leuven
ClinicalTrials.gov Identifier: NCT05169593    
Other Study ID Numbers: s62015
First Posted: December 27, 2021    Key Record Dates
Last Update Posted: March 17, 2023
Last Verified: March 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Universitaire Ziekenhuizen KU Leuven:
biological therapy
ileocolonoscopy
ileocolonic resection
ileocolonic anastomosis
Additional relevant MeSH terms:
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Crohn Disease
Recurrence
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Disease Attributes
Pathologic Processes
 Adalimumab
Infliximab
Ustekinumab
Vedolizumab
Anti-Inflammatory Agents
Antirheumatic Agents
Dermatologic Agents
Gastrointestinal Agents