Discontinuation of Infliximab Therapy in Patients With Crohn's Disease During Sustained Complete Remission

NCT01817426 | Completed Phase 4 DMC

• 1 other identifier: 02MA
• Study Type: interventional
• Target: 115
• Locations: 4 countries
• Sites: 13

Brief Summary

The purpose of this study is to determine whether infliximab can favourably and safely be discontinued in patients with Crohn's disease in sustained complete clinical, biochemical, and endoscopic remission on infliximab. Further to examine the clinical utility of measuring levels/activity of infliximab and activity of anti-infliximab Ab in patients in sustained complete remission, in order to investigate whether pharmacoimmunological data can predict the clinical outcome and rationalize therapeutic management of these patients with respect to continuation or discontinuation of infliximab therapy. Additional, to investigate the optimal time-point, out of three, to measure this activity.

Conditions

Crohn Disease

Outcome Measures

Primary Outcomes (1)

• Time to relapse after discontinuation of IFX

  Relapse defined as CDAI \>150 and an increase in CDAI from baseline \>70 over 2 consecutive weeks (or definitive relapse as judged by treating physician)

  48 weeks

Secondary Outcomes (5)

• Time to loss of remission

  48 weeks

• Proportion of patients who maintain clinical remission

  48 weeks

• Proportion of patients who maintain clinical and endoscopic remission

  48 weeks

• Proportion of patients who experience relapse (more stringent definition)

  48 weeks

• Proportion of patients who experience relapse

  48 weeks

Study Arms (2)

infliximab

ACTIVE COMPARATOR

Patients in this arm are randomized to continue IFX therapy at an unchanged dosage and frequency.

Drug: Infliximab

Placebo

PLACEBO COMPARATOR

Patients in this arm are randomized to receive matching placebo.

Other: Placebo

Interventions

Infliximab DRUG

Also known as: Remicade

infliximab

Placebo OTHER

Placebo

Eligibility Criteria

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

You may qualify if:

• Luminal Crohn's disease defined according to standardized diagnostic criteria.
• Age ≥ 18 years.
• IFX induction treatment week 0, 2, 6 followed by maintenance therapy.
• IFX treatment length minimum 12 months. Episodic therapy with IFX pause \> 12 weeks is not accepted within the last year. The treatment interval in the last three months has to be of 6-10 weeks.
• Complete remission defined as:
• CDAI score \< 150 and
• Biochemical remission, and
• No other signs of disease activity as evaluated by endoscopic examination or by magnetic resonance imaging (MRI).

You may not qualify if:

• Initial indication for IFX being predominantly fistulizing perianal disease.
• Any contraindications for continuing IFX treatment, including prior acute or delayed infusion reaction to a TNF- inhibiting agent, any active infection requiring parenteral or oral antibiotic treatment, known infection with tuberculosis, human immunodeficiency virus (HIV) or hepatitis virus.
• Any condition including physician finds incompatible with participation in the study or the patient being unwilling or unable to follow protocol requirements.

Sponsors & Collaborators

• Copenhagen University Hospital at Herlev: lead

Study Sites (13)

Aarhus University Hospital

Aarhus, Aarhus C, 8000, Denmark

Location

Bispebjerg Hospital

Copenhagen, Copenhagen NV, 2400, Denmark

Location

Nykøbing F. Sygehus

Nykøbing Falster, Nykøbing, 4800, Denmark

Location

Odense University hospital

Odense, Odense C, 5000, Denmark

Location

Herlev Hospital, department of gastroenterology medical section

Herlev, 2730, Denmark

Location

Hospital enheden vest Herning

Herning, Denmark

Location

Hvidovre Hospital

Hvidovre, Denmark

Location

Silkeborg Regional Hospital, Diagnostic Center

Silkeborg, Denmark

Location

Slagelse Sygehus

Slagelse, 4200, Denmark

Location

Helsinki University Hospital and University of Helsinki

Helsinki, Finland

Location

Akerhus University Hospital

Oslo, Norway

Location

Skane University Hospital

Lund, Sweden

Location

Karolinska Institute

Stockholm, Sweden

Location

Related Publications (2)

• Buhl S, Steenholdt C, Brynskov J, Christensen KR, Dorn-Rasmussen M, Thomsen OO, Bendtzen K, Klausen TW, Dahlerup JF, Thorsgaard N, Jahnsen J, Molazahi A, Pedersen N, Kjeldsen J, Almer S, Dahl EE, Vind I, Cannon AG, Marsal J, Sipponen T, Agnholt JS, Kievit HAL, Aure SL, Martinsen L, Meisner S, Hansen JM, Ainsworth MA. Discontinuation of Infliximab Therapy in Patients with Crohn's Disease. NEJM Evid. 2022 Aug;1(8):EVIDoa2200061. doi: 10.1056/EVIDoa2200061. Epub 2022 Jun 14.

  PMID: 38319804 DERIVED

• Buhl SS, Steenholdt C, Brynskov J, Thomsen OO, Bendtzen K, Ainsworth MA. Discontinuation of infliximab therapy in patients with Crohn's disease in sustained complete remission (the STOP IT study): protocol for a double-blind, randomised, placebo-controlled, multicentre trial. BMJ Open. 2014 Dec 18;4(12):e005887. doi: 10.1136/bmjopen-2014-005887.

  PMID: 25524543 DERIVED

MeSH Terms

Conditions

Crohn Disease

Interventions

Infliximab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Mark Ainsworth, MD.PHD.,DMSc

  Herlev Hospital, dep. of gastroenterology medical section.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Mark Ainsworth, MD, professor

Study Record Dates

• First Submitted: August 29, 2012
• First Posted: March 25, 2013
• Study Start: January 1, 2013
• Primary Completion: May 1, 2020
• Study Completion: May 1, 2020
• Last Updated: March 24, 2022

Record last verified: 2022-03

Locations

NO (1); DK (9); FI (1); SE (2)