ROSSINI-Platform - a 'Basket Factorial MAMS' Platform Trial in Surgical Site Infection

BACKGROUND

Surgical site infection (SSI) is the commonest surgical complication, incurring significant morbidity and mortality and huge costs to the health service. SSI is probably preventable and at a time of unprecedented pressure on the NHS it requires our urgent attention; current efforts to reduce SSI are failing and rates remain unacceptably high. The available evidence and national guidance are too generic and do not take into account the different pathways/pathogens of SSI across the body.

Multi-arm, multi-stage (MAMS) trials allow multiple individual interventions to be evaluated simultaneously, rendering them highly efficient. We have shown that MAMS trials can be delivered effectively in a modern surgical context with our HTA-funded ROSSINI 2 trial in abdominal SSI prevention.

We propose to expand this concept into a major multi-specialty platform trial. This will deliver multiple parallel RCTs in different surgical cohorts, utilising a ‘Basket Factorial MAMS’ design to simultaneously assess multiple interventions under one over-arching protocol and governance structure with active learning and cross-cohort transfer of interventions that suggest benefit.

This will provide robust and context-specific evidence in a highly efficient manner in terms of both time and cost. METHODS

A multi-speciality platform trial consisting of 6 individual full-scale pragmatic, outcome assessor blinded, stratified, multi-arm multi-stage 2x2x2 factorial RCTs. Internal pilot phases will run at platform, pillar and intervention levels. We will open 100 hospitals across the UK and recruit patients undergoing surgery in any of the following 6 surgical specialties (‘pillars’): Vascular groin, Major lower limb amputation (MLLA), Obstetric, Breast, Neurosurgery or Cardiac Surgery.

The trial will use context-specific eligibility criteria which vary by pillar. Individual pillars have each prioritised three specific intra- or peri-operative interventions to prevent SSI, based on: (i) evidence of potential clinical effectiveness, (ii) patient acceptability and (iii) clinician equipoise within their clinical area. A total of 18 interventions (15 unique to each other) are being assessed.

The primary outcome is SSI within 30 days of surgery, assessed at hospital discharge and then remotely through a pre-existing Central Digital Wound Hub (CDWH), augmented by questionnaires and wound photographs collected weekly via a patient-facing App (or via email/phone if preferred).

Each pillar is powered separately with sample sizes based on contemporaneous, evidence-based SSI rates and a pre-specified cross-pillar absolute risk reduction (ARR) strategy which is pinned to baseline SSI rate. Individual pillar maximum samples sizes are Vascular groin:3648; MLLA:2686; Obstetric:7266; Breast:4280; Neurosurgery:4280; Cardiac Surgery:3764. The maximum combined sample size across all pillars is 25,924 patients.

TIMELINES 60 month project: Set-up 7 months; Recruitment 50 months; Follow-up & close-down 3 months. IMPACT & DISSEMINATION

This major study will provide high-level evidence on the clinical efficacy and cost-effectiveness of many interventions to reduce surgical site infection. We will work with all key stakeholders to ensure implementation of measures that reduce SSI and de-adopt those that do not. The project has the potential to significant impact upon the rates of this highly impactful complication, thereby benefitting both patients and the health service.