Care Path for the Management of Ulcerative Colitis (CONSTRUCT)

A Cluster Randomized Controlled Trial of a Care-Path for the Management of Ulcerative Colitis

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.

Study Overview

• Status: Terminated
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Other: Enhanced treatment algorithm; Other: Usual Care

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.

• Study Type: Interventional
• Enrollment (Actual): 192
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Enhanced treatment algorithm; 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	Other: Enhanced treatment algorithm; Practitioners assigned to the intervention arm will be educated on the use of the Enhanced Algorithm.
Placebo Comparator: Usual Care; These subjects will be managed according to local treatment guidelines for the treatment of UC.	Other: Usual Care; usual step care practice

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients in remission at the end of 12 months.	Remission is defined as 1) a Mayo Clinic Score of ≤2 with rectal bleeding and stool frequency sub-scale scores of 0) with no use of corticosteroids, and 3) normalization of the subject's index inflammatory marker (c-reactive protein or calprotectin). The primary endpoint will be assessed at Month 12.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients in remission over the course of the study	The time in remission over the course of the study; occurrence of surgery or hospitalization for Ulcerative Colitis; occurrence of disease-related complications; health related QoL (Short-Form 36 questionnaire [SF-36] and EuroQoL instrument [EQ-5D]); and, subject	18 months

Collaborators and Investigators

• Sponsor: University of Western Ontario, Canada
• Investigators: Principal Investigator: Brian G Feagan, MD, Alimentiv Inc.

Publications and helpful links

General Publications

• 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.
• 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. Erratum In: Am J Gastroenterol. 2010 Mar;105(3):500.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): November 1, 2015
• Study Completion (Anticipated): May 1, 2016

Study Registration Dates

• First Submitted: June 17, 2013
• First Submitted That Met QC Criteria: June 19, 2013
• First Posted (Estimate): June 20, 2013

Study Record Updates

• Last Update Posted (Estimate): May 13, 2016
• Last Update Submitted That Met QC Criteria: May 12, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: Cluster randomization controlled trial; CONSTRUCT; Gastroenterology practices in North America
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: RP1206