Title: Clinical Evaluation and Regulatory Approval of the E-Vac, an Endoluminal Vacuum Therapy Device
Funder: Department of Health and Social Care

Abstract: Background Leaks from the upper gastrointestinal (GI) tract pose a significant management problem. Traditional treatments including surgery and enteral stenting are associated with significant mortality rates. More recently endoluminal vacuum therapy (EVT) has been used, achieving significantly lower mortality rates than other treatment methods for all upper GI leak causes. Currently, EVT is delivered using a bulky ad hoc device. The procedure requires a general anaesthetic, is time consuming, technically challenging, and poses a risk of further perforation during device insertion. These issues are compounded as the device is changed multiple times during treatment. Given the clear improvement in patient outcome, there is urgent need for a device that supports successful delivery of EVT while overcoming these problems. We have developed the E-Vac, a prototype EVT device that is easily and safely delivered without needing a general anaesthetic. The E-Vac has been used successfully to treat 2 patients. Aims The aims of the study are to finalise the E-Vac prototype, followed by a multi-centre clinical investigation to establish E-Vac s safety and efficacy in treating upper GI leaks, and a health economic analysis. On completion, we will apply for a CE mark for the E-Vac. Methods: The project has 4 phases, with 8 separate work packages(WP), and defined timelines and deliverables over 36 months. Phase1(Month 1-14); Tooling manufacture for the E-Vac(WP2). Production of training material, and adaptation of endoscopy mannequin to create a simulator for E-Vac training(WP1). Phase2(Month 5-27); Establishment of assembly and testing protocols for E-Vac, verification of device manufacture and assembly procedures, and establishment of sterilisation protocol(WP3). Evaluation questionnaires will be developed to capture feedback from clinicians and patients about E-Vacs useability and tolerability(WP4). Regulatory approvals for the clinical investigation will be obtained, and the study set up by the Cambridge Clinical Trials Unit(WP5). Phase3(Months 1-36); Multicentre clinical investigation conducted in 5 regional oesophagogastric centres, and health economic analysis. The study is a single arm prospective cohort study which will recruit 45 patients. Inclusion criteria for the study include age >18y, contained leak from the upper GI tract from any cause, and E-Vac planned as either primary or salvage treatment. Patient outcomes and procedure costs will be compared to historical cohorts of patients treated with surgery, and EVT using the ad hoc device(WP5,6). Phase4(Month 1-36); Submission of technical file to the MHRA for a CE mark, and results dissemination(WP7,8). Anticipated Impact and Dissemination: The primary outcome of the study will be a CE marked device with established tooling enabling future clinical studies, commercialisation, and wider dissemination within the NHS. This will be supported by a health economic analysis of both the E-Vac and procedure. The E-Vac training materials developed for the study will be available for future training events when opened to a wider audience. It is also anticipated the study database will form the basis for a future national database to capture E-Vac use and outcome data. The results of the study will be disseminated through presentations at relevant medical meetings, and published in a peer review journal.

Lay abstract: Each year, around 2,800 people in the UK get a hole in their upper bowel. Holes may occur on their own after violent vomiting, arise from problems such as stomach ulcers, or be caused accidentally during surgery or other medical interventions. Holes allow stomach contents to leak into the body and quickly cause infection around the heart and lungs, a serious medical emergency that is fatal if not successfully treated. The standard way of fixing these holes is surgery, but this often fails. More than half of patients die following surgery, especially if treatment is delayed(which is common). Recently, surgeons have invented a treatment called Endoluminal Vacuum Therapy(EVT). This consists of a special sponge on the end of a tube which is inserted into the hole in the stomach. The tube is used to suction out the leaked stomach contents and close the hole. EVT has been successful in patients where other treatments failed. However, EVT still needs improvement as it requires high skill levels to place the sponge, and a new device to be made for each operation. Each insertion also requires general anaesthesia. Successful EVT requires several insertions, meaning lots of operations for the patient, and high NHS costs. Therefore, we have developed the E-Vac , a pre-made device allowing easier sponge insertion without needing general anaesthesia. The E-Vac makes EVT quicker, easier and cheaper, and is less traumatic for patients. We are now applying for funding to develop the E-Vac so it can be mass produced and used widely within the NHS. We will: 1.Run a clinical trial using the E-Vac to treat 45 patients in 5 hospitals to check that it works and is safe. Patients and doctors will be asked how the E-Vac can be further improved. We will also produce guidance for medical staff on using the E-Vac. 2.We will explore potential costs and benefits to the NHS of using the E-Vac, compared to current treatments. 3.Once we know the E-Vac works safely, we will apply for an official CE mark , which shows it is safe and allows it to be sold. 4.We will use the trial results to provide information to NHS managers, clinicians and the public to help get E-Vac treatment into common practice. Three former upper bowel 'hole' patients and 2 of their partners have been involved in the development of this project from the beginning, to give an on-going patient perspective on E-Vac development. They have advised us on important ethical issues, particularly gaining consent from patients who are too unwell to respond actively, and contributed to this proposal and lay summary. They feel the planned work is important. We will continue to include them at key stages during the study.

Research activity codes: 6.3 MEDICAL DEVICES;5.3 MEDICAL DEVICES
Health categories: ORAL AND GASTROINTESTINAL