Enhanced Algorithm for Crohn's Treatment Incorporating Early Combination Therapy

Crohn's Disease Clinical Trial

— REACT2  

Official title:

A Cluster Randomized Controlled Trial of an Enhanced Treatment Algorithm for the Management of Crohn's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01698307
• Other study ID #: RP1202
• Status: Completed
• Phase: Phase 4
• Start date: March 28, 2014
• Est. completion date: April 16, 2020

Study information

• Verified date: November 2021
• Source: Alimentiv Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Assess if the implementation of an enhanced treatment algorithm will improve the management Crohn's Disease compared to a conventional Step-care approach.

Description:

Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract. During disease exacerbations, pharmacological or surgical intervention is usually needed to re-establish remission. Ideally, strategies should be employed to maintain patients in long-term remission while minimizing exposure to corticosteroids and reduce therapy-related toxicity. Nevertheless, in reality many patients with CD do not receive effective therapy and their disease often remains active, leading to uncontrolled inflammation and complications from either the underlying disease or corticosteroids.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1095
• Est. completion date: April 16, 2020
• Est. primary completion date: April 16, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Documented diagnosis of CD
• Written informed consent must be obtained and documented.
• Willing to utilize study supply of adalimumab provided in syringe format, if indicated according to treatment algorithm.

Exclusion Criteria:

• Any conditions (e.g., history of alcohol or substance abuse) which, in the opinion of the investigator, may interfere with the patient's ability to comply with study procedures.
• Latex allergy or other conditions in which adalimumab syringes are contraindicated
• Currently participating, or planning to participate in a study involving investigational product within 24 months that may interfere with the patient's ability to comply with study procedures.
• Previously failed all classes of tumor necrosis factor (TNF) antagonists for the treatment of CD.
• Diagnosis of short bowel syndrome

Related Conditions & MeSH terms

• Crohn Disease
• Crohn's Disease

Intervention

Other:
• Enhanced Treatment Algorithm
The Enhanced algorithm features the early use of combined antimetabolite/adalimumab therapy, and treatment intensification based on ileocolonoscopic findings. Failure to achieve or sustain Deep Remission, which includes sustained normalization of the imaging studies, will result in treatment intensification, according to the steps outlined in the algorithm, irrespective of symptoms.
• Conventional Step-care Algorithm
Step-care algorithm that specifies treatment escalation solely on the basis of symptoms quantified using the Harvey Bradshaw Score.

Locations

Country	Name	City	State
Canada	Duane Sheppard, GI Inc.	Dartmouth	Nova Scotia
Canada	The Office of Dr. Bruce Musgrave	Kentville	Nova Scotia
Canada	S. and T. Shulman Medicine Professional Corporation	North Bay	Ontario
Canada	Oravec Medicine Professional Corporation	Oshawa	Ontario
Canada	The Office of Dr. Pierre Laflamme	Saint-Charles-Borromée	Quebec
Canada	Sudbury Endoscopy Center	Sudbury	Ontario
Canada	Dr. Fashir Medical Inc.	Sydney	Nova Scotia
Germany	Praxis fur Gastroenterologie am Bayerischen Platz	Berlin
Germany	Gastroenterologie Eppendorfer Baum	Hamburg
Germany	Verein fur Wissenschaft und Fortbildung	Oldenburg	Lower Saxony
United Kingdom	The Royal Bournemouth Hospital	Bournemouth	Dorset
United Kingdom	University Hospital Coventry	Coventry	West Midlands
United Kingdom	Oxford University Hospitals NHS Foundation - John Radcliffe Hospital	Headington	Oxford
United Kingdom	Nottingham University Hospitals NHS Trust	Nottingham
United Kingdom	Royal Berkshire NHS Foundation Trust	Reading	Berkshire
United Kingdom	The Royal Hampshire County Hospital	Winchester	Hampshire
United Kingdom	New Cross Hospital - Royal Wolverhampton NHS Trust	Wolverhampton	West Midlands
United States	Asheville Gastroenterology Associates, PA	Asheville	North Carolina
United States	Louisiana Research Center, LLC	Shreveport	Louisiana
United States	Scott and White Memorial Hospital	Temple	Texas
United States	Carle Foundation Hospital	Urbana	Illinois
United States	Georgetown University Hospital	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Alimentiv Inc.

Countries where clinical trial is conducted

United States,  Canada,  Germany,  United Kingdom, 

References & Publications (5)

Colombel JF, Rutgeerts PJ, Sandborn WJ, Yang M, Camez A, Pollack PF, Thakkar RB, Robinson AM, Chen N, Mulani PM, Chao J. Adalimumab induces deep remission in patients with Crohn's disease. Clin Gastroenterol Hepatol. 2014 Mar;12(3):414-22.e5. doi: 10.1016/j.cgh.2013.06.019. Epub 2013 Jul 12. — View 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. — View 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, Ochsenkühn 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. — View Citation

Feagan BG, Panaccione R, Sandborn WJ, D'Haens GR, Schreiber S, Rutgeerts PJ, Loftus EV Jr, Lomax KG, Yu AP, Wu EQ, Chao J, Mulani P. Effects of adalimumab therapy on incidence of hospitalization and surgery in Crohn's disease: results from the CHARM study. Gastroenterology. 2008 Nov;135(5):1493-9. doi: 10.1053/j.gastro.2008.07.069. Epub 2008 Aug 3. — View Citation

Lichtenstein GR, Feagan BG, Cohen RD, Salzberg BA, Diamond RH, Chen DM, Pritchard ML, Sandborn WJ. Serious infections and mortality in association with therapies for Crohn's disease: TREAT registry. Clin Gastroenterol Hepatol. 2006 May;4(5):621-30. Erratum in: Clin Gastroenterol Hepatol. 2006 Jul;4(7):931. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Proportion of patients at one year and two years who are in Deep Remission without disease progression	Disease progression is defined as the de novo development of strictures or fistula, the occurrence of an intra-abdominal abscess, or surgery for Crohn's Disease (resection, bypass, stricturoplasty).	1 year, 2 years
Other	Proportion of patients at one year and two years who are in Deep Remission	Deep remission defined as a Harvey-Bradshaw Index (HBI) less than or equal to 4, no steriods for the treatment of Crohn's Disease, and normal C-reactive protein	1 year, 2 years
Other	Proportion of patients at one year and 2 years who are in Clinical Remission	Clinical remission defined as an Harvey-Bradshaw Index (HBI) of equal to or less than 4.	1 year, 2 years
Other	Change in C-reactive protein		6 months, 1 year, 2 years
Other	Change in health related QoL, patient and physician global rating	The EuroQoL instrument [EQ-5D] will be used to measure quality of life.	6 months, 1 year, 2 years
Other	Patient and physician satisfaction	At the completion of study participation, subjects and physicians in both treatment groups will be asked to complete a satisfaction questionnaire regarding the information provided and their overall satisfaction with the approach to the management of CD. The physicians will also be asked if they would recommend the CD treatment algorithm to their colleagues, and if they think it would be feasible to sustain this algorithm within their practice setting.	2 years
Primary	Risk of Crohn's Disease-related complications at two years	Crohn''s Disease (CD)-related complications include (1) CD-related surgeries and non-surgical CD events (such as disease flare, bowel obstruction, and bowel damage events (such as symptomatic bowel obstruction, fistula, abscess and CD related hospitalizations and 2) complications and hospitalizations related to CD medications or procedures.	2 years
Secondary	Risk of Crohn's Disease-related complications, Crohn's Disease-related hospitalizations, and all cause hospitalizations at 6 months and 12 months.	Crohn's Disease (CD)-related complications include (1) CD-related surgeries and non-surgical CD events (such as disease flare, bowel obstruction, and bowel damage events (such as symptomatic bowel obstruction, fistula, abscess and CD related hospitalizations and 2) complications and hospitalizations related to CD medications or procedures.	six months, 12 months
Secondary	Time to first Crohn's Disease-related complication, first Crohn's Disease-related hospitalizations, and first all cause hospitalizations at 6 months and 12 months.	Crohn's Disease (CD)-related complications include (1) CD-related surgeries and non-surgical CD events (such as disease flare, bowel obstruction, and bowel damage events (such as symptomatic bowel obstruction, fistula, abscess and CD related hospitalizations and 2) complications and hospitalizations related to CD medications or procedures.	six months, 12 months