Discontinuation of Infliximab Therapy in Patients With Crohn's Disease During Sustained Complete Remission (STOP IT)
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.
|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|
- Proportion of patients who maintain remission, i.e. CDAI <150 [ Time Frame: After one year ] [ Designated as safety issue: Yes ]
- 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.
- 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.
|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)|
Active Comparator: infliximab
Patients in this arm are randomized to continue IFX therapy at an unchanged dosage and frequency.
Other Name: Remicade
Placebo Comparator: Placebo
Patients in this arm are randomized to receive matching placebo.
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.
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).
|Contact: Sine Schnoor Buhl, M.D.||+45 firstname.lastname@example.org|
|Contact: Mark Ainsworth, MD. PHD. DMSc||Marain01@heh.regionh.dk|
|Herlev Hospital, department of gastroenterology medical section||Recruiting|
|Herlev, Denmark, 2730|
|Contact: Sine Schnoor Buhl, MD +45 51201207 email@example.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|
|Principal Investigator:||Mark Ainsworth, MD.PHD.,DMSc||Herlev Hospital, dep. of gastroenterology medical section.|