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

NCT05169593 | Recruiting Phase 4 DMC

• 1 other identifier: s62015
• Study Type: interventional
• Target: 292
• Locations: 2 countries
• Sites: 28

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.

Conditions

Crohn Disease

Keywords

biological therapy; ileocolonoscopy; ileocolonic resection; ileocolonic anastomosis

Outcome Measures

Primary Outcomes (2)

• postoperative endoscopic recurrence (Rutgeerts score ≥i2b)

  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

  86 weeks

• need for unscheduled treatment adaptation prior to week 86

  When, due to clinical symptoms, therapy needs to be started or switched prior to week 86

  86 weeks

Secondary Outcomes (6)

• Harvey Bradshaw Index (HBI) based clinical recurrence

  86 weeks

• Direct costs

  86 weeks

• new ileocolonic resection

  86 weeks

• Severe adverse reactions

  86 weeks

• Serious adverse events

  86 weeks

Other Outcomes (24)

• Crohn's disease activity index (CDAI) based clinical recurrence

  86 weeks

• Harvey Bradshaw Index (HBI score higher than 4) based clinical recurrence

  86 weeks

• Two-component Patient Reported Outcome (PRO-2) based clinical recurrence

  86 weeks

Study Arms (2)

Endoscopy-driven postoperative biological therapy

OTHER

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

Systematic postoperative prophylaxis with a biological

ACTIVE COMPARATOR

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

Interventions

Biological Drug DRUG

Biological therapy used in daily clinical practice in patients with Crohn's disease to prevent disease recurrence

Also known as: Risankizumab, Vedolizumab, Ustekinumab, Infliximab, Adalimumab

Endoscopy-driven postoperative biological therapy; Systematic postoperative prophylaxis with a biological

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures.
• Patients with a diagnosis of Crohn's disease based on radiology, endoscopy and/or histology
• Males and females 18-80 years old.
• 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.
• Patients having an increased risk for postoperative recurrence for any of the following reasons:
• Penetrating disease as reason for ileocolonic resection
• Previous ileocolonic resection within ten years of index surgery
• Two or more previous ileocolonic resections
• Active smoking
• Biological therapy for Crohn's disease within 3 months of index ileocolonic resection
• Curative ileocolonic resection. All inflamed colon segments should have been removed. Strictureplasties in the small bowel not involving the anastomotic region are allowed.
• 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.
• Patients able and willing to start and continue biological therapy, and this at the timepoint indicated through study randomization

You may not qualify if:

• 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..
• Any disorder, which in the Investigator's opinion might jeopardise the participant's safety or compliance with the protocol.
• Any prior or concomitant treatment(s) that might jeopardise the participant's safety or that would compromise the integrity of the Trial.
• Participation in an interventional Trial with an Investigational Medicinal Product (IMP) or device.
• Patients initiating biological therapy for CD as part of another clinical trial or a medical need program.
• Patients not understanding Dutch, French, German or English.
• Patients with ulcerative colitis or inflammatory bowel disease type unclassified.
• Patients with an ileorectal anastomosis, or an ileal pouch-anal anastomosis.
• Patients with active perianal disease.
• Patients with a colorectal stenosis.
• Patients with an ostomy.
• 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.
• Patients with (an imminent risk) of a short bowel syndrome.
• Patients who had qualifying ileocolonic resection for dysplasia or cancer without ongoing inflammation.
• 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).

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead

Study Sites (28)

ZAS

Antwerp, Antwerpen, 2018, Belgium

RECRUITING

UZA

Edegem, Antwerpen, 2650, Belgium

RECRUITING

Erasmus ziekenhuis

Brussels, Brussels Capital, 1070, Belgium

RECRUITING

Cliniques Universitaires Saint Luc

Brussels, Brussels Capital, 1200, Belgium

RECRUITING

UZ Brussel

Jette, Brussels Capital, 1090, Belgium

RECRUITING

CHwapi

Tournai, Henegouwen, 7500, Belgium

RECRUITING

ZOL Genk

Genk, Limburg, 3600, Belgium

RECRUITING

CHC Montlégia

Liège, Liège, 4000, Belgium

RECRUITING

CHU de Liège

Liège, Liège, 4000, Belgium

RECRUITING

CHU UCL Namur site Godinne

Yvoir, Namur, 5530, Belgium

NOT YET RECRUITING

AZ Maria Middelares

Ghent, Oost-Vlaanderen, 9000, Belgium

RECRUITING

UZ Gent

Ghent, Oost-Vlaanderen, 9000, Belgium

RECRUITING

UZ Leuven

Leuven, Vlaams-Brabant, 3000, Belgium

RECRUITING

Sint lucas Brugge

Bruges, West-Vlaanderen, 8310, Belgium

NOT YET RECRUITING

AZ Damiaan

Ostend, West-Vlaanderen, 8400, Belgium

RECRUITING

OLV Aalst

Aalst, 9300, Belgium

RECRUITING

Imeldaziekenhuis

Bonheiden, 2820, Belgium

RECRUITING

AZ Klina

Brasschaat, 2930, Belgium

RECRUITING

AZ Sint-Jan

Bruges, 8000, Belgium

RECRUITING

AZ Sint Lucas

Ghent, 9000, Belgium

RECRUITING

Jessa ziekenhuis

Hasselt, 3500, Belgium

RECRUITING

AZ Sint Maarten

Mechelen, 2800, Belgium

WITHDRAWN

AZ Delta

Roeselare, 8800, Belgium

RECRUITING

Vitaz

Sint-Niklaas, 9100, Belgium

RECRUITING

Humanitas research hospital

Milan, Rozzano MI, 20089, Italy

NOT YET RECRUITING

IRCCS De Bellis Castellana Grotte

Castellana Grotte, 70013, Italy

RECRUITING

Careggi University Hospital

Florence, 50134, Italy

RECRUITING

IRCCS San Raffael Hospital

Milan, 20132, Italy

RECRUITING

MeSH Terms

Conditions

Crohn Disease

Interventions

Biological Products; risankizumab; vedolizumab; Ustekinumab; Infliximab; Adalimumab

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Complex Mixtures; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Marc Ferrante, Professor

  IG/MAAG-DARM-LEVER, UZ Leuven, campus Gasthuisberg, Herestraat 49 3000 Leuven

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marc Ferrante, Professor

CONTACT

016 342845; marc.ferrante@uzleuven.be

Dorien Beeckmans, PhD

CONTACT

016 348545; dorien.beeckmans@uzleuven.be

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A randomized, multicentre, parallel group pragmatic non-inferiority trial

Study Record Dates

• First Submitted: November 8, 2021
• First Posted: December 27, 2021
• Study Start: September 8, 2022
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2030
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (4); BE (24)