Clinical trial NCT02716454: Early Surgery Versus Conservative Treatment in Patients With Ileocaecal Crohn's Disease
Official title: Early Surgery Versus Conservative Treatment in Patients With Ileocaecal Crohn's Disease - Prospective Randomized Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Crohn's Disease
Keywords: Early surgery
Crohn's disease
Step-up therapy
Lead sponsor: Czech Surgical Society
Sponsor class: OTHER
First posted: 2016-03-23
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study compares the efficacy of early surgical with medical treatment in patients with ileocaecal uncomplicated Crohn's disease. The patients with affected short part of terminal ileum will be randomized either for laparoscopic ileocaecal resection or standard step-up pharmacological therapy.

Detailed description: Surgical therapy is currently indicated for Crohn's disease (CD) patients after conservative treatment becomes ineffective. The principles of so-called step-up therapy (STUP) where surgery represents the last therapeutical option are still followed.

Early surgical intervention (Early Surgery - ES) can be an alternative even in patients with uncomplicated type of CD before all medical therapy is used (Top-down approach). Limited resection under these conditions will lead to immediate remission. Moreover, laparoscopic ileocaecal resection is safe with low morbidity and regarding potential complications of step-up treatment might be beneficial for the patient.

Before wide introduction of ES approach into clinical practice, it is necessary to perform a randomized trial comparing early resection with the standard step-up medical therapy.

The potential effect of early, intensive therapy (ileocaecal resection) on biological behavior of the disease has not been studied that is why patients with uncomplicated ileocaecal form are the most suitable for such a trial. Significant number of these patients will indeed progress into more unfavorable course of the disease (relapse, complicated form, early recurrence).

Other potential benefit of early resection is the extended period without necessary medication. Even pharmacological recurrence prevention is not needed after surgery in uncomplicated CD patient if other risk factors are excluded. Rapid remission induced by surgery can lead to faster improvement of quality of life than long-term medication.

Eligibility criteria: Inclusion criteria

* All patients aged 18-65 years with a uncomplicated ileocaecal form of Crohn's disease (affected \< 20 cm of terminal ileum) (type: L1B1) diagnosed within last 12 months
* Diagnose confirmed by endoscopy including appropriate extent of disease and presence of ulcers in terminal ileum
* Patient is able to understand the study and sign an informed consent

Exclusion Criteria:

* Pregnant or breastfeeding women
* Previous bowel resection or other extensive abdominal surgery, which primarily excludes laparoscopic approach
* Affected other parts of the digestive tract or symptomatic stenosis or stenosis impassable for the endoscope or presence of prestenotic dilatation in terminal ileum confirmed by enterography
* Any extraluminal complications of Crohn's disease (fistula, abscess)
* Affected part of terminal ileum longer than 20 cm
* Severe comorbidities (heart failure, renal failure, liver failure, severe disorders of the central and peripheral nervous system, serious infectious disease) or patient with ASA (American Society of Anesthesiologists) III and more
* Malnutrition or presence of another serious risk factor, which contradicts construction of primary anastomosis
* Current use of immunosuppressive or biologic therapy

Other exclusion criteria:

* Different intraoperative finding
* Protocol violation
* Subject refuses further participation in the study
* Termination of the trial by responsible authority

Primary outcomes:
measure: Endoscopic remission
timeFrame: 24 months
Secondary outcomes:
measure: QoL
timeFrame: 24 months
measure: Clinical remission
timeFrame: 24 months
measure: Drug consumption
timeFrame: 24 months
Other outcomes:
Locations:
city: Brno
country: Czech Republic
facility: The University Hospital Brno
city: Ceske Budejovice
country: Czech Republic
facility: Hospital Ceske Budejovice
city: Horovice
country: Czech Republic
facility: Horovice Hospital
city: Hradec Kralove
country: Czech Republic
facility: Universitiy Hospital Hradec Kralove
city: Jihlava
country: Czech Republic
facility: Hospital Jihlava
city: Liberec
country: Czech Republic
facility: Hospital Liberec
city: Ostrava - Vitkovice
country: Czech Republic
facility: Vitkovice Hospital
city: Pilsen
country: Czech Republic
facility: University Hospital in Pilsen
city: Prague
country: Czech Republic
facility: Royal Vinohrady University Hospital
city: Prague
country: Czech Republic
facility: Institute for Clinical and Experimental Medicine
city: Prague
country: Czech Republic
facility: Na Homolce Hospital
city: Prague
country: Czech Republic
facility: ISCARE
Study officials:
affiliation: Section of IBD surgery - Czech Surgical Society
name: Ondrej Ryska, Dr, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jess T, Riis L, Vind I, Winther KV, Borg S, Binder V, Langholz E, Thomsen OO, Munkholm P. Changes in clinical characteristics, course, and prognosis of inflammatory bowel disease during the last 5 decades: a population-based study from Copenhagen, Denmark. Inflamm Bowel Dis. 2007 Apr;13(4):481-9. doi: 10.1002/ibd.20036.
citation: Domenech E, Zabana Y, Garcia-Planella E, Lopez San Roman A, Nos P, Ginard D, Gordillo J, Martinez-Silva F, Beltran B, Manosa M, Cabre E, Gassull MA. Clinical outcome of newly diagnosed Crohn's disease: a comparative, retrospective study before and after infliximab availability. Aliment Pharmacol Ther. 2010 Jan 15;31(2):233-9. doi: 10.1111/j.1365-2036.2009.04170.x. Epub 2009 Oct 13.
citation: Cosnes J, Nion-Larmurier I, Beaugerie L, Afchain P, Tiret E, Gendre JP. Impact of the increasing use of immunosuppressants in Crohn's disease on the need for intestinal surgery. Gut. 2005 Feb;54(2):237-41. doi: 10.1136/gut.2004.045294.
citation: Golovics PA, Lakatos L, Nagy A, Pandur T, Szita I, Balogh M, Molnar C, Komaromi E, Lovasz BD, Mandel M, Veres G, Kiss LS, Vegh Z, Lakatos PL. Is early limited surgery associated with a more benign disease course in Crohn's disease? World J Gastroenterol. 2013 Nov 21;19(43):7701-10. doi: 10.3748/wjg.v19.i43.7701.
citation: Eshuis EJ, Bemelman WA, van Bodegraven AA, Sprangers MA, Bossuyt PM, van Milligen de Wit AW, Crolla RM, Cahen DL, Oostenbrug LE, Sosef MN, Voorburg AM, Davids PH, van der Woude CJ, Lange J, Mallant RC, Boom MJ, Lieverse RJ, van der Zaag ES, Houben MH, Vecht J, Pierik RE, van Ditzhuijsen TJ, Prins HA, Marsman WA, Stockmann HB, Brink MA, Consten EC, van der Werf SD, Marinelli AW, Jansen JM, Gerhards MF, Bolwerk CJ, Stassen LP, Spanier BW, Bilgen EJ, van Berkel AM, Cense HA, van Heukelem HA, van de Laar A, Slot WB, Eijsbouts QA, van Ooteghem NA, van Wagensveld B, van den Brande JM, van Geloven AA, Bruin KF, Maring JK, Oldenburg B, van Hillegersberg R, de Jong DJ, Bleichrodt R, van der Peet DL, Dekkers PE, Goei TH, Stokkers PC. Laparoscopic ileocolic resection versus infliximab treatment of distal ileitis in Crohn's disease: a randomized multicenter trial (LIR!C-trial). BMC Surg. 2008 Aug 22;8:15. doi: 10.1186/1471-2482-8-15.
citation: Rutgeerts P, Geboes K, Vantrappen G, Beyls J, Kerremans R, Hiele M. Predictability of the postoperative course of Crohn's disease. Gastroenterology. 1990 Oct;99(4):956-63. doi: 10.1016/0016-5085(90)90613-6.
citation: Peyrin-Biroulet L, Cieza A, Sandborn WJ, Coenen M, Chowers Y, Hibi T, Kostanjsek N, Stucki G, Colombel JF; International Programme to Develop New Indexes for Crohn's Disease (IPNIC) group. Development of the first disability index for inflammatory bowel disease based on the international classification of functioning, disability and health. Gut. 2012 Feb;61(2):241-7. doi: 10.1136/gutjnl-2011-300049. Epub 2011 Jun 5.
citation: Dignass A, Van Assche G, Lindsay JO, Lemann M, Soderholm J, Colombel JF, Danese S, D'Hoore A, Gassull M, Gomollon F, Hommes DW, Michetti P, O'Morain C, Oresland T, Windsor A, Stange EF, Travis SP; European Crohn's and Colitis Organisation (ECCO). The second European evidence-based Consensus on the diagnosis and management of Crohn's disease: Current management. J Crohns Colitis. 2010 Feb;4(1):28-62. doi: 10.1016/j.crohns.2009.12.002. Epub 2010 Jan 15. No abstract available.
citation: Maartense S, Dunker MS, Slors JF, Cuesta MA, Pierik EG, Gouma DJ, Hommes DW, Sprangers MA, Bemelman WA. Laparoscopic-assisted versus open ileocolic resection for Crohn's disease: a randomized trial. Ann Surg. 2006 Feb;243(2):143-9; discussion 150-3. doi: 10.1097/01.sla.0000197318.37459.ec.
citation: Aratari A, Papi C, Leandro G, Viscido A, Capurso L, Caprilli R. Early versus late surgery for ileo-caecal Crohn's disease. Aliment Pharmacol Ther. 2007 Nov 15;26(10):1303-12. doi: 10.1111/j.1365-2036.2007.03515.x. Epub 2007 Sep 10.