Title: CONservative TReatment of Appendicitis in Children – a randomised controlled Trial – CONTRACT (Feasibility study)
Funder: Department of Health and Social Care

Abstract: DESIGN: (1) prospective multi-centre randomised controlled feasibility trial to determine the feasibility of performing a future definitive RCT comparing emergency appendicectomy with a non-operative treatment pathway in children with uncomplicated acute appendicitis; (2) embedded qualitative and survey research to facilitate optimisation of recruitment to, and design and conduct of future RCT; (3) development of a core outcome set (COS) for this intervention. SETTING: Three specialist NHS Paediatric Surgical Units in England. TARGET POPULATION: Children (age 4-15 years) with a clinical diagnosis of acute uncomplicated appendicitis. HEALTH TECHNOLOGY BEING ASSESSED: The treatment of children with acute uncomplicated appendicitis with a non-operative treatment pathway involving treatment with antibiotics (intravenous followed by oral) and regular clinical review to ensure disease resolution. Participants will be randomised to either ‘appendicectomy’ or ‘non-operative treatment’. MEASUREMENT OF COSTS AND OUTCOMES: The principal outcome measure of this feasibility study will be recruitment rate. We will also assess the accuracy of our clinical assessment at predicting uncomplicated appendicitis, the ease of use of the protocol and treatment pathways and test data collection systems. Clinical outcomes will be recorded. The embedded qualitative study will explore parental and surgeon views of the trial with a focus to improving design and implementation of the future RCT. To inform a full economic evaluation of our future RCT we will identify key cost drivers in this feasibility study and test data capture methods. We will determine the most appropriate health related quality of life assessment tool to use in the RCT. We will develop a COS for this intervention and population using a protocol driven Delphi consensus method involving multiple stakeholder groups. This will identify important and relevant outcomes to measure in our future RCT. SAMPLE SIZE: We anticipate a minimum of 130 eligible patients and recruitment in the range of 40-50%. This will allow estimation of a true 40% recruitment rate with a 95%CI of 31%-49% and a true 50% recruitment rate with a 95%CI of 41%-59%. We estimate 52-65 participants in our feasibility RCT, 40 families and 20 paediatric surgeons contributing to our qualitative research and 40 surgeons and 80 patients/parents contributing to the development of the COS. PROJECT TIMETABLES AND RECRUITMENT RATE: Total study duration 28 months. Formation of our PPI advisory group will take place in month 1. A 6 month lead-up phase before recruitment begins will allow for generation of recruitment material, ethical approval, governance procedures, training of the recruiting staff, centre set-up and obtaining NHS permissions. Subsequent key activity includes recruitment to RCT (12 months); clinical follow-up and data collection (6 months); centre closure, final analysis and report writing (4 months). The embedded qualitative work and the development of a COS will take place during this period. EXPERTISE IN TEAM: The team has extensive experience in the design and conduct of RCTs in surgery and in children, trial methodology, surgical expertise, statistical analysis of RCTs, qualitative methods, feasibility studies involving children, COS development and health economic analysis of interventions in children. The study is supported by a CTU and has strong PPI involvement.

Lay abstract: “Can you treat my child without an operation?” is frequently asked by parents of children with acute appendicitis, the commonest condition in children treated with emergency surgery. Currently the answer is “No” as the gold-standard treatment is an operation called an appendicectomy in which the appendix is removed. Recently, however, it has become clear in adults that antibiotics may be as good as an operation for acute appendicitis and the majority of adults can avoid an operation altogether. We do not know whether this is the case for children with appendicitis but we believe the timing is right for a careful research study to find out the answer. The overall aim of our research is to answer the question: ‘Is surgery necessary for children with acute appendicitis?’ To answer our question we plan to perform a large study comparing 2 groups of children with appendicitis – one group will have surgery and the other will be treated with antibiotics. However before we do this we need to see if running such a study will be achievable. It would be wrong to commit significant resources to such a study if it is unlikely to be possible to complete. This project is therefore a feasibility study in 3 related parts. We will perform a small trial which will randomly allocate children with appendicitis to have either an appendicectomy or non-operative treatment with antibiotics. The study will be carried out in 3 specialist Children’s Surgery centres and last for 1 year. We will see how many patients and families are willing to join the study and will look at how well children in the study recover. This will give us an indication of how many children we may be able to recruit into our future larger trial and how the outcomes of non-operative treatment compare with an operation. Although this may give us an idea of whether it is possible to safely treat children who have appendicitis with antibiotics, it will not provide a definitive answer. Embedded within this trial we will carry out some other research to find out the reasons for wanting or not wanting to join a trial such as this through careful discussion with patients and their parents. In those who have been involved we will find out how they found the experience. In particular we will ask what we can do to improve the trial from the families’ perspective. We will assess surgeon willingness to recruit patients into the study as measured by recruitment rates and explore clinician attitudes to the study by discussion. We will approach surgeons in the centres involved in the study and also across the whole of the UK. We envisage that all of this information will enable us to improve the design of our future trial so that it has the greatest possible chance of success. Finally we will ask parents, patients, and surgeons what they think are the most important outcomes for children with acute appendicitis treated without an operation. We will develop an essential list of outcomes that should be measured. We will measure these in our future trial, so we can be certain we record important outcomes that are most likely to influence parental decisions and surgeon practice in the future. All of the information gathered from the 3 parts of our study will enable us to design and complete a larger study in the future. This larger study is what will be needed to demonstrate whether the two types of treatment (surgery or antibiotics) are as effective as each other

Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING
Health categories: ORAL AND GASTROINTESTINAL