Title: The feasibility of undertaking Appendicectomy to impact upon the Clinical Course of UlceRativE Colitis - The ACCURE Trial Feasibility study
Funder: Department of Health (England)

Abstract: Background Ulcerative Colitis (UC) is a chronic inflammatory condition affecting the colon with a 40% annual relapse rate. Patients usually respond to escalation of medication, but 25% will ultimately require major surgery to remove the whole colon. A severe refractory attack of colitis can require emergency surgery; this is high risk surgery with a complication rate in excess of 30% and many months of recovery. Many patients will also be left with a stoma. Previous research has shown that the appendix can affect the development and activity of UC. Large cohort studies have shown that people who have undergone appendicectomy are less likely to develop UC in the first place. Research in-vitro and with animal models has confirmed the important role of the appendix in gut immunity and identified pathways by which appendicectomy could plausibly impact upon UC disease activity. More recently, several small clinical studies in active UC have found that appendicectomy produces a significant improvement in symptoms with fewer future relapses, hospitalisations and lower medication usage as well as potentially preventing the need for major emergency surgery in the future. Aims Our overall research aim is to determine if appendicectomy results in an improved clinical course compared to standard medical therapy in adult patients with established ulcerative colitis. This initial feasibility phase is necessary to establish if the proposed intervention, a minor surgical operation, is an attractive treatment option to UC sufferers and clinicians, and to estimate the morbidity profile of the intervention. Information will be obtained about the relapse rate in the control arm which will inform sample size calculations for a future RCT exploring clinical efficacy. Finally, patient accrual, follow-up tools and adherence will be assessed, which will be invaluable in designing the full RCT. Plan of Investigation This multicentre randomised controlled trial will recruit adult patients with an established diagnosis of ulcerative colitis and a disease relapse within 12 months of randomisation, medically treated until full clinical remission. Patients will be randomised 1:1 between control (standardised medical care) and intervention (elective laparoscopic appendectomy plus standardised medical care). We will establish the numbers of eligible and randomised patients in each centre, ascertain optimal recruitment pathways and identify and tackle emerging barriers to recruitment. Patients undergoing appendicectomy will be closely followed to record operative demographics, length of stay and 30 day complication rate. Health resource usage data and health-related quality of life information will be recorded for all patients in both arms Finally, the one-year clinical follow-up structure proposed for the full RCT will be applied to all patients to provide an estimate of the relapse rate in the control arm and to assess follow-up tools and likely attrition rates for the potential full trial. Qualitative research with patients and clinicians will provide a detailed picture of key stakeholder perspectives on trial acceptability, design and processes, thereby contributing to the design of a definitive study Potential benefits to patients and the NHS If an appendicectomy can protect UC patients from future use of medication, hospital admission and thereby the need for major colonic resectional surgery, the initial minor morbidity from appendicectomy will be offset by substantial long-term gain in health and quality of life, as well as reduced health resource usage. This intervention is not currently employed as a therapeutic treatment for UC in the NHS. If we can demonstrate that appendicectomy is an efficacious and cost-effective strategy that is acceptable to patients, widespread uptake can be anticipated, affecting many hundreds of patients every year and reducing prolonged periods of illness, health service resource usage and the need for major surgical intervention.


Research activity codes: 6.4 SURGERY
Health categories: ORAL AND GASTROINTESTINAL