Condition category
Digestive System
Date applied
12/08/2019
Date assigned
03/09/2019
Last edited
03/09/2019
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Ulcerative colitis (UC) is a form of inflammatory bowel disease. Symptoms of the disease include diarrhoea, abdominal pain and an increase in the need to use the toilet. Patients can go for months with no, or very mild symptoms (remission) and then suffer a flare-up (relapse) where symptoms become much more severe; hospital treatment can become necessary in the worse cases. There is some evidence that the appendix has a role in the regulation of inflammation within the bowel, and that removing the appendix (appendicectomy, also commonly known as appendectomy in Europe/the US) may have a positive impact on how active UC is. Results from a previous study also show that appendicectomy is safe and attractive to patients and their doctors and had better outcomes. However, the study was not designed to be large enough to prove any definite benefit. This study is a larger clinical study to complement a study currently being carried out in The Netherlands using the same design and study procedures. This will allow the researchers to combine their findings with the Dutch group in one large analysis, thereby obtaining a more robust result and in a more timely fashion. The overall aim of the research is to find out whether removing the appendix (appendicectomy) can reduce the chances of a patient experiencing further flare-ups of their Ulcerative Colitis (UC) in the future months.

Who can participate?
Patients aged 18 or over with proven ulcerative colitis who have experienced a flare-up of disease symptoms within the last 12 months, but with currently little or no disease activity (remission)

What does the study involve?
First, patients are checked to see if they are in remission by examining the large bowel with a camera (endoscopy). This may be accompanied by testing a stool sample (faeces) for signs of inflammation (faecal calprotectin test). If the patient agrees to participate in the study, they are asked to sign a consent form and then asked to complete questionnaires about their quality of life. They are asked to complete the same questionnaires every 3 months for 1 year. The participant is then randomly allocated to either the appendicectomy group or the ‘control’ or comparison group. Those in the appendicectomy group have an operation to remove their appendix, continuing with their usual medication(s). Those in the control group simply continue with their usual medication(s). After this stage, follow-up involves regular reviews to discuss symptoms and complete further questionnaires. These reviews are scheduled to take place at around 6 weeks (appendicectomy group only for standard post-operative checks), 3, 6, 9 and 12 months after entry to the study and take place in hospital at outpatient clinics. However, the reviews at 3, 6 and 9 months may be done over the telephone. At the end of the trial (12 months) participants are asked to undergo one final camera examination of their bowel. If during the 12 months periods, the participant feels they are developing symptoms of a flare, they are asked to contact the research team at their hospital to arrange an urgent review, and possibly blood tests and a camera examination of the bowel.

What are the possible benefits and risks of participating?
For participants in the control group, there will be no disadvantages from a medical point of view as they will receive standard treatment with medications as they would anyway. Additionally, the reviews planned every 3 months throughout the trial (with the exception of the final 12-month review) can be completed over the phone if visit the outpatient clinics are not always convenient. The only additional burdens are the camera tests at the beginning and end of the study. In addition, the appendicectomy group will have an operation, which is an additional treatment compared to the routine care of patients with UC. Like any surgery there is always the possibility of complications. The researchers have done their best to reduce the chances of these by ensuring that only experienced and specialised colorectal consultant surgeons undertake operations during the trial. All adverse events relating to the operations within the study will be carefully recorded as this is important information to know if this operation is offered more widely to UC patients. For participants in the control group, there is unlikely to be any personal benefit from taking part in the trial, although they will undergo a period of careful disease and medical treatment monitoring. Some patients will draw satisfaction from the knowledge that their involvement, in either group, will help determine if this new proposed treatment has the potential to benefit all patients affected by UC. For the appendicectomy group, if the operation does prove to have an impact on the disease activity in UC, there may be a potential benefit to an individual patient in taking part in terms of reducing the number or severity of disease relapses. This may in turn impact upon the future use of medication, number of hospital admissions and the need for major bowel surgery.

Where is the study run from?
The study will run across the UK including at least 10 hospitals including in Birmingham, Leicester, Cambridge, Sheffield and London.

When is the study starting and how long is it expected to run for?
May 2019 to November 2021

Who is funding the study?
National Institute for Health Research (NIHR): Efficacy and Mechanism Evaluation (EME) Programme (UK)

Who is the main contact?
James Brown
j.p.brown.1@bham.ac.uk

Trial website

www.birmingham.ac.uk/ACCURE-UK2

Contact information

Type

Public

Primary contact

Mr James Brown

ORCID ID

http://orcid.org/0000-0003-4513-1509

Contact details

Birmingham Clinical Trials Unit
Public Health Building
University of Birmingham
Birmingham
B29 2TT
United Kingdom
+44 (0)121 414 9012
j.p.brown.1@bham.ac.uk

Type

Scientific

Additional contact

Prof Thomas Pinkney

ORCID ID

http://orcid.org/0000-0001-7320-6673

Contact details

Birmingham Clinical Trials Unit
Public Health Building
University of Birmingham
Birmingham
B29 2TT
United Kingdom
+44 (0)121 414 9012
thomas.pinkney@uhb.nhs.uk

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

CPMS: 40580

Study information

Scientific title

An international multicentre randomised controlled trial to assess the effect of Appendectomy on the Clinical Course of ulcerative colitis; UK arm

Acronym

ACCURE-UK 2

Study hypothesis

Appendicectomy will result in an improved clinical course in UC compared to those undergoing standard care, with an increased chance of maintaining remission and an associated improvement in overall symptoms.

Ethics approval

Approved 29/07/2019, East Midlands - Leicester South Research Ethics Committee (The Old Chapel, Royal Standard Place, Nottingham, NG1 6FS, UK; Tel: +44 (0)207 104 8109; +44 (0)207 104 8036; Email: NRESCommittee.EastMidlands-LeicesterSouth@nhs.net), ref: 19/EM/0191

Study design

Multi-centre phase 3 two-arm outcome-assessor blinded prospective randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

Ulcerative colitis

Intervention

This UK study will recruit 90 UC patients currently in disease remission and randomly allocate them into one of two groups, the appendicectomy group or the control group. Those in the control group take their standard tablet medication as usual. Those in the appendicectomy group also take their usual medication but they also undergo an appendicectomy. All patients will then be followed up for one year with information about disease activity, medication use, health-related quality of life, health resource usage obtained.

Intervention type

Procedure/Surgery

Phase

Drug names

Primary outcome measure

One-year UC relapse rate (defined both clinically and endoscopically as Mayo score ≥5 with endoscopy
subscore of 2 or 3)

Secondary outcome measures

1. Number of relapses per patient at 12 months
2. Time to first relapse
3. Health-related quality of life and costs measured using (EQ-5D-3L, EORTC-QLQ-C30-QL and IBDQ at 3, 6, 9 and 12 months post-randomisation
4. Disease activity measured with the Mayo score at 12 months or relapse
5. Colectomy rate at 12 months
6. Resource usage, including medication usage, diagnostic tests undergone outside of the trial (laboratory work, radiological and endoscopic assessments), inpatient costs and health professional interactions

Overall trial start date

01/05/2019

Overall trial end date

01/11/2021

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Histologically confirmed Ulcerative Colitis
2. Disease relapse within 12 months of randomisation medically treated until remission
3. In clinical remission at time of randomisation with partial Mayo score less than 3 and presumptive endoscopic Mayo subscore of 0 or 1, identified by endoscopy (within 3 months). The endoscopy will be either:
3.1. Colonoscopy examining the full length of the colon and rectum
3.2. Sigmoidoscopy examining the last part of the colon (sigmoid and rectum) with faecal calprotectin less than 150 ug/g
4. Aged 18 or over
5. Patient able and willing to give written informed consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 272

Participant exclusion criteria

1. Previous appendicectomy or other major abdominal surgery precluding safe laparoscopic appendicectomy
2. Any suspicion of Crohn’s disease
3. Disease recently treated with biologicals (within 3 months of randomisation)
4. Severe disease ever treated with biologicals and stopped due to secondary non-response
5. Toxic megacolon or severe ongoing active colitis at time of randomisation
6. Patients with significant comorbidity (e.g. unstable heart failure, liver or kidney failure, major lung co-morbidity)

Recruitment start date

03/09/2019

Recruitment end date

01/07/2020

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Queen Elizabeth Hospital Birmingham
University Hospitals Birmingham NHS Foundation Trust Mindelsohn Way
Birmingham
B15 2WB
United Kingdom

Trial participating centre

Queen Elizabeth Hospital Birmingham
University Hospitals Birmingham NHS Foundation Trust Bordesley Green East
Birmingham
B9 5ST
United Kingdom

Trial participating centre

Leicester Royal Infirmary
University Hospitals of Leicester NHS Trust Infirmary Square
Leicester
LE1 5WW
United Kingdom

Trial participating centre

St Marks Hospital
London North West University Healthcare NHS Trust Watford Road
Harrow
HA1 3UJ
United Kingdom

Trial participating centre

Addenbrooke's Hospital
Cambridge University Hospitals NHS Foundation Trust Hills Road
Cambridge
CB2 0QQ
United Kingdom

Trial participating centre

Northern General Hospital
Sheffield Teaching Hospitals NHS Foundation Trust Herries Road
Sheffield
S5 7AU
United Kingdom

Sponsor information

Organisation

University of Birmingham

Sponsor details

c/o Dr Birgit Whitman
Room 117
Aston Webb Building
Edgbaston
Birmingham
B15 2TT
United Kingdom
+44 (0)121 415 8011
researchgovernance@contacts.bham.ac.uk

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

NIHR Evaluation, Trials and Studies Co-ordinating Centre (NETSCC); Grant Codes: 16/61/35

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

The protocol is available on the ACCURE-UK 2 website (https://www.birmingham.ac.uk/ACCURE-UK2). The findings will be published in international medical journals, publicised on the trial website and presented at relevant conferences.

IPD sharing statement
The datasets generated during and/or analysed during the current study are/will be available upon request from Dr Laura Magill (e.l.magill@bham.ac.uk). Access to available anonymised data may be granted following review.

Intention to publish date

31/10/2022

Participant level data

Available on request

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

12/08/2019: Trial's existence confirmed by the NIHR.