ROSSINI II Trial - Reduction Of Surgical Site Infection using several Novel Interventions. A multi-arm, multi-stage surgical RCT utilising an adaptive design

Design: Multi-arm, multi-stage (MAMS) pragmatic multicentre RCT exploring the use of three in-theatre interventions to reduce SSI. Non-factorial design with allocation of various combinations of the three interventions to be used during the same operation, via seven possible treatment arms initially. Predefined interim analyses will be undertaken at two points during the trial; two arms will be dropped after each analysis. Setting: Multiple NHS hospitals in the UK. Target population: Adults undergoing abdominal surgery. Inclusion criteria: Adults undergoing abdominal surgery for any indication - including colorectal, hepatobiliary, upper GI, urological, vascular, gynae operations via any incision, both emergency and elective. Laparoscopic-assisted abdominal operations with a specimen extraction site of at least 5cm also eligible. Exclusion criteria: Age< 18 years; unable to give informed consent; previous laparotomy within the past 3 months. Health technologies being assessed and their control arms: 1) 2% alcoholic chlorhexidine skin prep – versus any other standard skin prep routinely used 2) Ioban-impregnated incise drape – versus none 3) Gentamicin-impregnated collagen implants at closure – versus none Outcomes: Primary – SSI within 30 days of surgery, assessed by blinded clinicians at 5-7 and 30-35 days, and by patient’s self-report for intervening period Secondary - Health-related quality of life assessed using the EQ-5D questionnaire, Health resource usage and the incremental cost-effectiveness of the interventions compared to standard care; Adverse events. Difference between current and planned care pathways: This pragmatic trial is designed to have minimal impact upon a patient’s standard clinical care and thereby enhance acceptability and recruitment levels, whilst maximising follow-up rates. The only additional procedures for this trial are as follows: i) consent and HR-QOL at baseline (pre-op) ii) in-theatre randomisation – to maintain blinding and minimise attrition/cross-over rates iii) in-person wound review by a blinded, clinically trained observer at 5-7 days (pre-discharge) and 30-33 days. Sample size: 6613 patients. Based on control arm SSI rate of 15% reduced to 10% in intervention arm(s); power 85%; FWER 0.025. Three stages; two interim and one final. First analysis at 2357 patients, second at 4632 pts. After each interim analysis two intervention arms dropped. Selection of arms to be dropped undertaken using a composite of clinician acceptability, adherence to arm allocation and clinical effectiveness. Project timetable: Funding is requested for a 48 month (4 year) project. 6 months - set up 6 months - internal pilot (10 sites) 32 months recruitment from 62 sites; opening sites at 4 per month during main phase; each open site recruiting 4 pts per month. 4 months - completion/final analysis Expertise: We have assembled a large and multidisciplinary research team to deliver this trial, with a proven track record in creating large surgical RCTs delivered through an established network of over 115 surgical units, who will work in close conjunction with the world leaders in complex trial design and analysis. The team also includes the founders and current leaders of trainee-led research, who will form an important core of trial management and delivery. There is also expert representation in health economics, microbiology and PPI, including service user representatives.