Prevention of Postoperative Endoscopic Recurrence with Endoscopy-driven Versus Systematic Biological Therapy

Last updated: December 5, 2024
Sponsor: Universitaire Ziekenhuizen KU Leuven
Overall Status: Active - Recruiting

Phase

4

Condition

N/A

Treatment

Biological Drug

Clinical Study ID

NCT05169593
s62015
  • Ages 18-80
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Voluntary written informed consent of the participant or their legally authorizedrepresentative has been obtained prior to any screening procedures.

  2. Patients with a diagnosis of Crohn's disease based on radiology, endoscopy and/orhistology

  3. Males and females 18-80 years old.

  4. Patients undergoing an ileocolonic resection with ileocolonic anastomosis (with orwithout temporary ileostomy) within 3 and 40 days prior to the Screening visit. Patients who underwent an ileocolonic resection with ileocolonic anastomosis with atemporary ileostomy are also eligible if the ileocolonic resection was performedwithin eight months prior to the Screening visit, and the restoration of the faecalstream was performed within 3 and 40 days prior to the Screening visit.

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

  6. Penetrating disease as reason for ileocolonic resection

  7. Previous ileocolonic resection within ten years of index surgery

  8. Two or more previous ileocolonic resections

  9. Active smoking

  10. Biological therapy for Crohn's disease within 3 months of index ileocolonicresection

  11. Curative ileocolonic resection. All inflamed colon segments should have beenremoved. Strictureplasties in the small bowel not involving the anastomotic regionare allowed.

  12. Patients previously failing at least three months of steroids and/or three months ofimmunosuppressive therapy, or showing intolerance or a real contraindication for anyof these therapies.

  13. Patients able and willing to start and continue biological therapy, and this at thetimepoint indicated through study randomization

Exclusion

Exclusion Criteria:

  1. Participant has a history of primary non response or secondary loss of response toall 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'ssafety or compliance with the protocol.

  3. Any prior or concomitant treatment(s) that might jeopardise the participant's safetyor 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 amedical 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 ofantibiotics for more than ten days after ileocolonic resection or restoration of thefaecal stream.

  13. Patients with (an imminent risk) of a short bowel syndrome.

  14. Patients who had qualifying ileocolonic resection for dysplasia or cancer withoutongoing inflammation.

  15. Patients with liver test abnormalities (aspartate transaminase, alaninetransaminase, 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.

Study Design

Total Participants: 292
Treatment Group(s): 1
Primary Treatment: Biological Drug
Phase: 4
Study Start date:
September 08, 2022
Estimated Completion Date:
October 31, 2030

Study Description

This will be a prospective, randomized, parallel group, pragmatic trial.

Prior to study group assignment, the type of biological therapy to be (eventually) used in the postoperative phase will be selected by the treating physician after thorough discussion with the patient. The use of cheaper anti-TNF biosimilars will be encouraged, but patients who received adalimumab and/or infliximab preoperatively cannot receive the same treatment again in SOPRANO CD if the participants previously encountered immunogenicity issues to this treatment.

Systematic postoperative prophylaxis with a biological:

Biological therapy (adalimumab, infliximab, ustekinumab, vedolizumab or risankizumab) will be initiated within 14 to 40 days after ileocolonic resection or restoration of the faecal stream (day 0).

In patients with both Harvey-Bradshaw Index (HBI) based clinical recurrence (HBI >4) and endoscopic recurrence (Rutgeerts score ≥i2b) at week 30, biological therapy will be optimized (reimbursed or through the available free goods / samples programs).

Beyond week 32 optimization of this biological therapy will be allowed following daily clinical practice including proactive therapeutic drug monitoring. However, the timing, type and reason for dose optimization should be recorded.

Endoscopy-driven postoperative biological therapy:

No CD related therapy will be administered between Baseline (14 to 40 days after ileocolonic resection or restoration of the faecal stream) and the endoscopic evaluation at week 30 Patients with endoscopic recurrence (Rutgeerts score ≥i2b) at week 30 will initiate biological therapy (adalimumab, infliximab, ustekinumab, vedolizumab or risankizumab) following a classical induction and maintenance schedule. The type of biological therapy has to be decided already in the perioperative phase to allow a proper stratification.

In patients initiating biological therapy at week 30, this therapy maybe optimized from week 32 onwards following daily clinical practice including proactive therapeutic drug monitoring. However, the timing, type and reason for dose optimization should be recorded.

In patients not on biological therapy yet but developing clinical recurrence (HBI >4) with objective signs of disease recurrence (faecal calprotectin >250 µg/g, C-reactive protein >5 mg/L or endoscopic recurrence ≥i2b or clear radiological disease activity at the neo-terminal ileum) beyond week 32, biological therapy can be initiated, but this will be regarded as a study failure.

Randomization:

Eligible patients will be allocated to one of the two treatment arms (1:1) according to a computer generated randomisation list in REDCap.

Stratified randomisation will be performed to achieve approximate balance for:

  • Type of selected postoperative prophylactic therapy: adalimumab, infliximab, ustekinumab, vedolizumab or risankizumab.

  • Number of risk factors for postoperative recurrence: 1, 2 or >2 (out of 5 predefined factors: active smoking, penetrating disease, previous ileocolonic resection ≤10 years of index surgery, ≥2 previous ileocolonic resections, biological therapy ≤3 months of index ileocolonic resection)

Connect with a study center

  • UZA

    Edegem, Antwerpen 2650
    Belgium

    Active - Recruiting

  • AZ Turnhout

    Turnhout, Antwerpen 2300
    Belgium

    Site Not Available

  • UZ Brussel

    Jette, Brussel 1090
    Belgium

    Active - Recruiting

  • CHwapi

    Tournai, Henegouwen 7500
    Belgium

    Active - Recruiting

  • ZOL Genk

    Genk, Limburg 3600
    Belgium

    Active - Recruiting

  • CHU UCL Namur site Godinne

    Yvoir, Namur 5530
    Belgium

    Site Not Available

  • AZ Maria Middelares

    Gent, Oost-Vlaanderen 9000
    Belgium

    Active - Recruiting

  • UZ Gent

    Gent, Oost-Vlaanderen 9000
    Belgium

    Active - Recruiting

  • UZ Leuven

    Leuven, Vlaams-Brabant 3000
    Belgium

    Active - Recruiting

  • Sint lucas Brugge

    Brugge, West-Vlaanderen 8310
    Belgium

    Site Not Available

  • AZ Damiaan

    Oostende, West-Vlaanderen 8400
    Belgium

    Active - Recruiting

  • OLV Aalst

    Aalst, 9300
    Belgium

    Active - Recruiting

  • GZA

    Antwerpen, 2018
    Belgium

    Active - Recruiting

  • Imeldaziekenhuis

    Bonheiden, 2820
    Belgium

    Active - Recruiting

  • AZ Klina

    Brasschaat, 2930
    Belgium

    Active - Recruiting

  • AZ Sint-Jan

    Brugge, 8000
    Belgium

    Active - Recruiting

  • Cliniques Universitaires Saint Luc

    Brussel, 1200
    Belgium

    Active - Recruiting

  • Erasmus ziekenhuis

    Brussel, 1070
    Belgium

    Active - Recruiting

  • AZ Sint Lucas

    Gent, 9000
    Belgium

    Active - Recruiting

  • Jessa ziekenhuis

    Hasselt, 3500
    Belgium

    Active - Recruiting

  • CHC Montlégia

    Liège, 4000
    Belgium

    Active - Recruiting

  • CHU de Liège

    Liège, 4000
    Belgium

    Active - Recruiting

  • AZ Sint Maarten

    Mechelen, 2800
    Belgium

    Active - Recruiting

  • AZ Delta

    Roeselare, 8800
    Belgium

    Active - Recruiting

  • Vitaz

    Sint-Niklaas, 9100
    Belgium

    Active - Recruiting

  • Humanitas research hospital

    Milano, Rozzano Mi 20089
    Italy

    Site Not Available

  • IRCCS De Bellis Castellana Grotte

    Castellana Grotte, 70013
    Italy

    Active - Recruiting

  • Careggi University Hospital

    Firenze, 50134
    Italy

    Active - Recruiting

  • IRCCS San Raffael Hospital

    Milano, 20132
    Italy

    Active - Recruiting

  • Azienda Ospedale Universita di padova

    Padova, 35128
    Italy

    Site Not Available

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