The ACCURE-trial: the effect of appendectomy on the clinical course of ulcerative colitis, a randomised international multicenter trial (NTR2883) and the ACCURE-UK trial: a randomised external pilot trial (ISRCTN56523019).

Tjibbe J Gardenbroek ,Laura Magill,Tom Seerden,Shrikanth Pathmakanthan,Rachel West,Baljit Singh,Saloomeh Sahami,Mark Löwenberg,Dmitri Negpodiev,Ye Htun Oo,Tariq Iqbal,Geert R D’haens ,I A M J Broeders ,Marcel G W Dijkgraaf ,Dion Morton ,Gijs R Van Den Brink ,Rebecca J Howard ,Maarten J Boom ,Michael F Gerhards ,Rosalie C Mallant-Hent ,Thomas Pinkney ,Yaïr I Z Acherman ,Christianne J Buskens ,Pieter J Tanis ,Bart A Van Wagensveld ,Guido H H Mannaerts ,Hendrikus J.m Pullens ,Pieter Stokkers ,J Van Der Vecht ,Robert Pierik ,Annick B Van Nunen ,Cyriel Y Ponsioen ,Meindert N Sosef ,Jeroen M Jansen ,Annekatrien Depla ,Willem A Bemelman

doi:10.1186/s12893-015-0017-1

Abstract

BackgroundOver the past 20 years evidence has accumulated confirming the immunomodulatory role of the appendix in ulcerative colitis (UC). This led to the idea that appendectomy might alter the clinical course of established UC. The objective of this body of research is to evaluate the short-term and medium-term efficacy of appendectomy to maintain remission in patients with UC, and to establish the acceptability and cost-effectiveness of the intervention compared to standard treatment.Methods/DesignThese paired phase III multicenter prospective randomised studies will include patients over 18 years of age with an established diagnosis of ulcerative colitis and a disease relapse within 12 months prior to randomisation. Patients need to have been medically treated until complete clinical (Mayo score <3) and endoscopic (Mayo score 0 or 1) remission. Patients will then be randomised 1:1 to a control group (maintenance 5-ASA treatment, no appendectomy) or elective laparoscopic appendectomy plus maintenance treatment. The primary outcome measure is the one year cumulative UC relapse rate - defined both clinically and endoscopically as a total Mayo-score ≥5 with endoscopic subscore of 2 or 3. Secondary outcomes that will be assessed include the number of relapses per patient at 12 months, the time to first relapse, health related quality of life and treatment costs, and number of colectomies in each arm.DiscussionThe ACCURE and ACCURE-UK trials will provide evidence on the role and acceptability of appendectomy in the treatment of ulcerative colitis and the effects of appendectomy on the disease course.Trial registrationNTR2883; ISRCTN56523019

Highlights

Over the past 20 years evidence has accumulated confirming the immunomodulatory role of the appendix in ulcerative colitis (UC)
In a systematic review we have shown that appendectomy might influence the disease course in UC patients, with possible reductions in relapse rates, need for immunosuppression and colectomy rates in UC patients who had an appendectomy, the heterogeneity of the available studies and subjective nature of the endpoints made direct comparison difficult [11]
1) ACCURE Trial (Netherlands) - A multicenter randomised clinical trial aiming at patients with an established diagnosis of ulcerative colitis and a disease relapse within 12 months prior to randomisation, medically treated until full clinical and endoscopic remission has been achieved as defined by the Mayo score

Summary

Discussion

Chronic relapsing diseases such as ulcerative colitis (UC) incur a considerable long-term health burden to the patients and health care systems. If the ACCURE-UK randomised feasibility trial shows that the intervention appears to be acceptable to clinicians and patients in the UK, and sufficient patients can be recruited and followed-up, we anticipate undertaking further parallel major multicentre phase III trial of the intervention in the UK in the year or two. Together, these two trials will provide a powerful evidence base of the clinical efficacy of the intervention in a diverse cohort.

Background

Methods/Design

Study design

Findings