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

NCT ID: NCT05169593

Last Updated: 2024-12-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

292 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-09-08

Study Completion Date

2030-10-31

Brief Summary

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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.

Detailed Description

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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)

Conditions

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Crohn Disease

Keywords

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biological therapy ileocolonoscopy ileocolonic resection ileocolonic anastomosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

A randomized, multicentre, parallel group pragmatic non-inferiority trial
Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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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.

Group Type OTHER

Biological Drug

Intervention Type DRUG

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

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.

Group Type ACTIVE_COMPARATOR

Biological Drug

Intervention Type DRUG

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

Interventions

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Biological Drug

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

Intervention Type DRUG

Other Intervention Names

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Risankizumab Vedolizumab Ustekinumab Infliximab Adalimumab

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Universitaire Ziekenhuizen KU Leuven

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Marc Ferrante, Professor

Role: PRINCIPAL_INVESTIGATOR

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

Locations

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GZA

Antwerp, Antwerpen, Belgium

Site Status RECRUITING

UZA

Edegem, Antwerpen, Belgium

Site Status RECRUITING

Erasmus ziekenhuis

Brussels, Brussels Capital, Belgium

Site Status RECRUITING

Cliniques Universitaires Saint Luc

Brussels, Brussels Capital, Belgium

Site Status RECRUITING

UZ Brussel

Jette, Brussels Capital, Belgium

Site Status RECRUITING

CHwapi

Tournai, Henegouwen, Belgium

Site Status RECRUITING

ZOL Genk

Genk, Limburg, Belgium

Site Status RECRUITING

CHC Montlégia

Liège, Liège, Belgium

Site Status RECRUITING

CHU de Liège

Liège, Liège, Belgium

Site Status RECRUITING

CHU UCL Namur site Godinne

Yvoir, Namur, Belgium

Site Status NOT_YET_RECRUITING

AZ Maria Middelares

Ghent, Oost-Vlaanderen, Belgium

Site Status RECRUITING

UZ Gent

Ghent, Oost-Vlaanderen, Belgium

Site Status RECRUITING

UZ Leuven

Leuven, Vlaams-Brabant, Belgium

Site Status RECRUITING

Sint lucas Brugge

Bruges, West-Vlaanderen, Belgium

Site Status NOT_YET_RECRUITING

AZ Damiaan

Ostend, West-Vlaanderen, Belgium

Site Status RECRUITING

OLV Aalst

Aalst, , Belgium

Site Status RECRUITING

Imeldaziekenhuis

Bonheiden, , Belgium

Site Status RECRUITING

AZ Klina

Brasschaat, , Belgium

Site Status RECRUITING

AZ Sint-Jan

Bruges, , Belgium

Site Status RECRUITING

AZ Sint Lucas

Ghent, , Belgium

Site Status RECRUITING

Jessa ziekenhuis

Hasselt, , Belgium

Site Status RECRUITING

AZ Sint Maarten

Mechelen, , Belgium

Site Status RECRUITING

AZ Delta

Roeselare, , Belgium

Site Status RECRUITING

Vitaz

Sint-Niklaas, , Belgium

Site Status RECRUITING

Humanitas research hospital

Milan, Rozzano MI, Italy

Site Status NOT_YET_RECRUITING

IRCCS De Bellis Castellana Grotte

Castellana Grotte, , Italy

Site Status RECRUITING

Careggi University Hospital

Florence, , Italy

Site Status RECRUITING

IRCCS San Raffael Hospital

Milan, , Italy

Site Status RECRUITING

Countries

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Belgium Italy

Central Contacts

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Marc Ferrante, Professor

Role: CONTACT

Phone: 016 342845

Email: [email protected]

Dorien Beeckmans, PhD

Role: CONTACT

Phone: 016 348545

Email: [email protected]

Facility Contacts

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Filip Couturier, MD

Role: primary

Michaël Somers, MD

Role: primary

Denis Franchimont, MD

Role: primary

Olivier Dewit, MD

Role: primary

Liv Vandermeulen, MD

Role: primary

Maxence Lefebvre, MD

Role: primary

Evelien Humblet, MD

Role: primary

Arnaud Colard, MD

Role: primary

Edouard Louis, MD

Role: primary

Jean-Francois rahier, prof

Role: primary

Didier Baert, MD

Role: primary

Triana Lobaton Ortega, MD

Role: primary

Marc Ferrante, MD

Role: primary

Dorien Beeckmans, PhD

Role: backup

Julie Busschaert, MD

Role: primary

Guy Lambrecht, MD

Role: primary

Stijn Vanden Branden, MD

Role: primary

Lieven Pouillon, MD

Role: primary

Evi Van Dyck, MD

Role: primary

Barbara Willandt, MD

Role: primary

Harald Peeters, MD

Role: primary

Liesbeth Thijs, MD

Role: primary

Jurgen Van Dongen, MD

Role: primary

Filip Baert, MD

Role: primary

Tom Holvoet, MD

Role: primary

Alessandro Armuzzi, Prof

Role: primary

Mauro Mastronardi

Role: primary

Gabriele Dragoni, MD

Role: primary

Silvio Danese, MD

Role: primary

Other Identifiers

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s62015

Identifier Type: -

Identifier Source: org_study_id