Trial record 2 of 12 for:    stop-it

Discontinuation of Infliximab Therapy in Patients With Crohn's Disease During Sustained Complete Remission (STOP IT)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2012 by Copenhagen University Hospital at Herlev
Sponsor:
Information provided by (Responsible Party):
Copenhagen University Hospital at Herlev
ClinicalTrials.gov Identifier:
NCT01817426
First received: August 29, 2012
Last updated: March 20, 2013
Last verified: August 2012
  Purpose

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.


Condition Intervention Phase
Crohn Disease
Drug: Infliximab
Other: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Discontinuation of Infliximab Therapy in Patients With Crohn's Disease During Sustained Complete Remission: A National Multi-center, Double Blinded, Randomized, Placebo Controlled Study

Resource links provided by NLM:


Further study details as provided by Copenhagen University Hospital at Herlev:

Primary Outcome Measures:
  • Proportion of patients who maintain remission, i.e. CDAI <150 [ Time Frame: After one year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Proportion of patients who maintain complete remission [ Time Frame: one year ] [ Designated as safety issue: Yes ]
  • Proportion of patients experiencing relapse [ Time Frame: after one year ] [ Designated as safety issue: Yes ]
  • Median time to relapse after discontinuation of IFX [ Time Frame: one year ] [ Designated as safety issue: Yes ]
  • Change from baseline in disease activity. [ Time Frame: after one year ] [ Designated as safety issue: Yes ]
    Evaluated by: CDAI as assessed by CDAI score, quality of life (QoL) as assessed by short-IBDQ, work productivity and activity as assessed by WPAI, biochemical markers assessed by, i.e. C-reactive protein (CRP), platelets, white blood cell (WBC) count, Hemoglobin (Hb) and fecal calprotectin and colonoscopy (scored by the Simple Endocopic Score for Crohn's Disease (SES-CD)) / MR imaging.

  • Direct medical costs in the to groups [ Time Frame: after one year ] [ Designated as safety issue: No ]
    Direct medical costs e.g. surgery, hospitalization, laboratory and radiological tests, and drug therapy.


Other Outcome Measures:
  • The clinical utility of measuring levels/activity of IFX and activity of anti-IFX Ab in patients in sustained complete remission. Additional, we will investigate the optimal time-point, out of three, to measure this activity. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Levels (by common solid - and fluid phase assays and at different time-point) of IFX and anti-IFX Ab relations to outcome; relapse, continued complete remission, and remission.


Estimated Enrollment: 139
Study Start Date: November 2012
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: infliximab
Patients in this arm are randomized to continue IFX therapy at an unchanged dosage and frequency.
Drug: Infliximab
Other Name: Remicade
Placebo Comparator: Placebo
Patients in this arm are randomized to receive matching placebo.
Other: Placebo

Detailed Description:

Recent guidelines for the management of Crohn's disease conclude that currently available data are insufficient to make firm recommendations on when and in whom to stop TNF-α antibody (TNF-α Ab) treatment after having obtained clinical remission. Further, the term "remission" is not well uniformly defined and may incorporate one or more features such as clinical remission, as assessed by CDAI, biochemical remission, endoscopical remission etc. The recently published prospective STORI study of 115 patients with luminal Crohn's disease reported that 56% of patients with Crohn's disease who had discontinued infliximab (IFX) while in clinical remission, maintained remission one year after discontinuation of therapy. Predictors of relapse included certain clinical features as well as objective biochemical and endoscopical markers of disease activity. Consistent with these data, we have recently reported that 61% of our own patients with Crohn's disease, who discontinued IFX while in complete clinical, steroid free IFX induced remission, maintained remission after one year; and half the patients were still in remission after nearly two years (median 680 days [412-948]).

A prospective randomized study of patients with Crohn's disease is necessary to confirm and extend the limited findings above, and assess whether IFX can be safely discontinued in a selected subgroup of patients with complete clinical, biochemical, and endoscopical remission.

Methods:

Study design: Prospective, double-blinded, randomized, placebo-controlled, Danish multi-center study with estimated seven Danish participating centers. Patients and treating physicians are blinded for the type of intervention.

Study population: Patients with luminal Crohn's disease in sustained complete remission on IFX.

Study treatment: Patients are randomized to either continue IFX treatment at an unchanged dosage and frequency, or alternatively to receive matching placebo. All patients will be graded for disease activity (Crohn's Disease Activity Index (CDAI), biochemical parameters, endoscopy, and/or MRI). Following screening and inclusion patients are seen after four weeks, and then every eight weeks. Endpoints are assessed at 12 months.

Investigators will, as explorative analyses, examine the clinical utility of measuring IFX levels and antibodies against IFX in patients with 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 IFX therapy. Additional, investigators will investigate the optimal time-point out of three to measure this activity. Patients will on the day of infusion have three blood samples drawn: one just before infusion (trough), one right after the infusion (obtained from the other arm)(peak) and one an hour after infusion (C1). Samples will be measured by common solid - and fluid phase assays for this purpose, e.g. Reporter Gene Assay (RGA).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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).
  • Stable remission, judged by the treating physician, at two consecutive treatments visits corresponding 2 scheduled IFX infusions. Thus, the first visit is during IFX maintaining therapy (screening visit). The second visit is at time of inclusion corresponding time of next scheduled IFX infusion (i.e. after ≈ 8 weeks).
  • No use of oral steroids within 3 months prior to inclusion.
  • Concomitant therapy with other immune suppressants, except steroids, is allowed. The dosage and frequency must have been stable three months prior to inclusion and must remain stable throughout the study period.

Exclusion Criteria:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01817426

Contacts
Contact: Sine Schnoor Buhl, M.D. +45 51201207 sine_buhl@hotmail.com
Contact: Mark Ainsworth, MD. PHD. DMSc Marain01@heh.regionh.dk

Locations
Denmark
Herlev Hospital, department of gastroenterology medical section Recruiting
Herlev, Denmark, 2730
Contact: Sine Schnoor Buhl, MD    +45 51201207    sine_buhl@hotmail.com   
Sub-Investigator: Sine Schnoor Buhl, MD         
Principal Investigator: Mark Ainsworth, MD.,PhD.,DMSc         
Sub-Investigator: Jørn Brynskov, M.D., DMSc         
Sub-Investigator: Casper Steenholdt, MD         
Sub-Investigator: Ole Østergaard Thomsen, M.D., DMSc         
Sub-Investigator: Klaus Bendtzen, Professor, M.D., DMSc         
Sponsors and Collaborators
Copenhagen University Hospital at Herlev
Investigators
Principal Investigator: Mark Ainsworth, MD.PHD.,DMSc Herlev Hospital, dep. of gastroenterology medical section.
  More Information

No publications provided

Responsible Party: Copenhagen University Hospital at Herlev
ClinicalTrials.gov Identifier: NCT01817426     History of Changes
Other Study ID Numbers: 02MA
Study First Received: August 29, 2012
Last Updated: March 20, 2013
Health Authority: Denmark: Danish Health and Medicines Authority

Additional relevant MeSH terms:
Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Infliximab
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Dermatologic Agents
Gastrointestinal Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 22, 2014