Clinical trial NCT01882426: Care Path for the Management of Ulcerative Colitis
Official title: A Cluster Randomized Controlled Trial of a Care-Path for the Management of Ulcerative Colitis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Ulcerative Colitis
Keywords: CONSTRUCT
Cluster randomization controlled trial
Gastroenterology practices in North America
Lead sponsor: University of Western Ontario, Canada
Sponsor class: OTHER
First posted: 2013-06-20
Enrollment: 192
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Assess if standardized care-path that features objective evaluations of disease activity and time-bound algorithms is superior to usual step-care in the treatment of ulcerative colitis.

Detailed description: Step-care based on symptomatic response remains the overwhelming algorithm of choice in clinical practice. Many subjects receive infliximab only as a last resort, when the subject is very ill and has failed repeated attempts of corticosteroid induction therapy. Although this situation is far from ideal, to change such entrenched physician behavior will require compelling evidence that Step-care results in inferior outcomes to earlier introduction of effective therapy.

Based on these considerations, we will perform a cluster randomization trial in which 40 gastroenterology practices will be randomly assigned to a treatment algorithm featuring the early use of combination therapy, treatment intensification guided by objective assessments of inflammation and the use of remission as a therapeutic goal or a conventional Step-care approach.

Eligibility criteria: Inclusion Criteria:

* Females of child bearing potential must have a negative serum pregnancy test prior to randomization, and must use a hormonal (oral, implantable or injectable) or barrier method of birth control throughout the study. Females unable to bear children must have documentation of such in the source records -- - Documented diagnosis of UC with a Mayo Clinic Score (MCS) ≥6 and a baseline Mayo Endoscopy Score \>2.
* Either an elevated serum C-reactive protein (CRP) (above the Upper Level of Normal (ULN) according to local laboratory results) or elevated fecal calprotectin (\> 250 mg/kg) concentration.
* Requires sigmoidoscopic evaluation at baseline (standard of care)
* Written informed consent must be obtained and documented.
* Ability of subject to participate fully in all aspects of this clinical trial in the opinion of the investigator.

Exclusion Criteria:

* Previous failure of TNF antagonist therapy
* Received any investigational drug in the past 30 days or 5 half-lives, whichever is longer.
* Pregnant or lactating women.
* Any conditions (e.g., history of alcohol or substance abuse) which in the opinion of the investigator, may interfere with the subject's ability to comply with study procedures.

Primary outcomes:
measure: Proportion of patients in remission at the end of 12 months.
timeFrame: 12 months
Secondary outcomes:
measure: Proportion of patients in remission over the course of the study
timeFrame: 18 months
Other outcomes:
Locations:
Study officials:
affiliation: Alimentiv Inc.
name: Brian G Feagan, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kornbluth A, Sachar DB; Practice Parameters Committee of the American College of Gastroenterology. Ulcerative colitis practice guidelines in adults: American College Of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol. 2010 Mar;105(3):501-23; quiz 524. doi: 10.1038/ajg.2009.727. Epub 2010 Jan 12.
citation: D'Haens G, Baert F, van Assche G, Caenepeel P, Vergauwe P, Tuynman H, De Vos M, van Deventer S, Stitt L, Donner A, Vermeire S, Van De Mierop FJ, Coche JR, van der Woude J, Ochsenkuhn T, van Bodegraven AA, Van Hootegem PP, Lambrecht GL, Mana F, Rutgeerts P, Feagan BG, Hommes D; Belgian Inflammatory Bowel Disease Research Group; North-Holland Gut Club. Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease: an open randomised trial. Lancet. 2008 Feb 23;371(9613):660-667. doi: 10.1016/S0140-6736(08)60304-9.
citation: Colombel JF, Sandborn WJ, Reinisch W, Mantzaris GJ, Kornbluth A, Rachmilewitz D, Lichtiger S, D'Haens G, Diamond RH, Broussard DL, Tang KL, van der Woude CJ, Rutgeerts P; SONIC Study Group. Infliximab, azathioprine, or combination therapy for Crohn's disease. N Engl J Med. 2010 Apr 15;362(15):1383-95. doi: 10.1056/NEJMoa0904492.
citation: Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N Engl J Med. 1987 Dec 24;317(26):1625-9. doi: 10.1056/NEJM198712243172603.
citation: D'Haens G, Sandborn WJ, Feagan BG, Geboes K, Hanauer SB, Irvine EJ, Lemann M, Marteau P, Rutgeerts P, Scholmerich J, Sutherland LR. A review of activity indices and efficacy end points for clinical trials of medical therapy in adults with ulcerative colitis. Gastroenterology. 2007 Feb;132(2):763-86. doi: 10.1053/j.gastro.2006.12.038. Epub 2006 Dec 20. No abstract available.