There are no additional COVID-19 risks from participation in ROSSINI 2. However, there will be long-reaching or even permanent changes to the NHS structures for delivering both patient care and clinical research as a result of COVID-19. As a result of these, we have slightly amended some trial processes and pathways in ROSSINI 2 whilst protecting the scientific and methodological integrity of the trial.

Please Note: We are now home-based during the COVID-19 pandemic but available and working. Responses may, however, take longer than normal as staff may be working altered hours. Please do not contact our usual office/landline number and instead email the trial contact and copy in the trial mailbox. If a query requires a prompt response, please mark as ‘urgent’ in the email subject header.

Surgical site infection (SSI) is a significant problem for patients and the health service, but is potentially preventable. Up to 25% of patients undergoing an abdominal surgical procedure develop an SSI and at an average cost of £3500 per SSI, it has been estimated that SSIs currently cost the NHS around £700 million per year, largely through prolonged postoperative inpatient stay and additional inpatient and outpatient treatment costs.

There is a significant health need for the ROSSINI 2 trial to address the problem of SSI, with benefit for both patients and the NHS. 

Primary objective

To determine whether three specific in-theatre interventions, used alone or in combination, result in decreased rates of SSI up to 30 days post-operation in adult patients undergoing abdominal surgery.

Clinical

-Do the intraoperative interventions used alone, or in various combinations (within seven possible intervention arms and one control arm) reduce the overall rate of SSI after abdominal surgery?

-Is the efficacy of the intervention/treatment arm dependent upon:

• degree of wound contamination (clean, clean-contaminated, contaminated, dirty)?
• patient comorbidity (e.g. diabetes, smoking, obesity)?
• duration of operation?
• stoma formation?
• operation approach?
• SARS-CoV-2 virus status on day of surgery?
• SARS-CoV-2 antibody status on day of surgery?

-Do the intraoperative interventions:

• have an acceptable safety profile?
• reduce the rates of wound complications?
• reduce the rates of mortality?

-What is the impact of SARS-CoV-2 virus infection status on overall SSI rate, and in those who previously had COVID-19 (proven or suspected), is there a time-dependent impact upon overall SSI rates? 

Economic

-Does the use of the interventions:

• improve health-related QoL?
• reduce the length of stay in hospital?
• reduce wound complication related hospital re-admissions?
• reduce the occurrence of unplanned wound reopening and/ or re-operations?
• are cost-effective?

Primary Outcome Measures

Surgical site infection(s) up to 30 days post operation will be assessed by a trained blinded assessor, by patient’s self-report and defined according to the internationally accredited Centers for Disease Control and Prevention criteria (CDC). 

Secondary Outcome Measures

• 30-day postoperative mortality rate (POMR).
• 30-day postoperative wound complication rate (Clavien-Dindo classification).
• Serious Adverse Events up to 30 days (wound or intervention-related only).
• Length of hospital stay after surgery as measured from the date of surgery to the date of discharge.
• Hospital re-admission for wound related complications within 30 days.
• Occurrence of unplanned wound reopening and/or re-operations within 30 days post-operation.
• Preference-based QoL measure (EQ-5D-5L) at Baseline, Day 7 (or discharge) and Day 30.
• Cost effectiveness (using Resource Use questionnaire).

ROSSINI 2 is a Multi-arm, multi-stage (MAMS) pragmatic, multicentre, randomised controlled trial, with an internal pilot, exploring the use of three separate in-theatre interventions, use alone or in combination, to reduce SSI. A non-factorial design with allocation of various combinations of the three interventions to be used during the same operation, via seven possible intervention arms plus a control arm initially.

The trial would be the first of its kind in a surgical setting. In addition to generating new knowledge in our primary research area, by utilising this advanced design in the context of our relatively simple primary endpoint of SSI, it will also pave the way for future efficient and rapid trials in other aspects of surgical care.

The three interventions chosen in ROSSINI 2 impact different phases of perioperative case and as such can be used either in isolation or in conjunction with each other and although there may potentially be interaction between the interventions (positive or negative) they appear to be mechanistically disparate.

The interventions are:

• 2% alcoholic chlorhexidine skin prep
• Iodophor-impregnated incise drapes
• Gentamicin-impregnated sponge

10 local NHS hospitals will participate in the pilot phase of ROSSINI 2 and at least 60 NHS hospitals in the UK will participant in the main phase of ROSSINI 2.

Approximately 6610 patients will be required to detect a 5% absolute risk reduction in the interventions arm(s) (15% to 10%) with 85% power.

Centre and surgeon eligibility

Any centre performing emergency and/or elective abdominal surgery will be eligible to participate in ROSSINI 2. Sites entering the trial must not be routinely using these interventions and be willing to accept patients being randomised to receive (or not receive) each of them, including combinations thereof. Surgeons must be willing to adhere to arm allocation and be willing to be trained in a standardised application technique.

Patient Inclusion Criteria

• Patients undergoing colorectal, hepatobiliary, upper GI, urological, vascular, or gynaecological operations.
• Patients undergoing abdominal operations (open or laparoscopic extraction site) with a planned incision of at least 5cm.
• Patients aged 16 years or older.
• Patients able and willing to undergo wound assessment (in person or remotely via telemedicine) at day 30-37 after surgery. 
• Patients able and willing to give written informed consent.
• All contamination strata, including clean, clean-contaminated, contaminated or dirty surgery.
• Patients undergoing planned (elective or expedited) or unplanned (emergency) surgery.

Patient Exclusion Criteria

• Previous laparotomy within 3 months prior to randomisation.
• Known to be pregnant or currently breast feeding
• Operations where the wound is not anticipated to be closed primarily 

Additional Notes:

• SARS-COV-2 virus status and antibody status on day of surgery – all patients are eligible to enter the trial regardless of positivity, negativity or not tested status; this information is collected to allow us to control against these factors in the analyses.
• Patients with a new or documented allergy/ intolerance to any of the study interventions (chlorhexidine, iodine, collagen or gentamicin) will not be randomised to an arm containing this intervention, but will still be eligible for recruitment to other arms of the study.
• Patients with end-stage renal failure where gentamicin administration would otherwise be contra-indicated (according to local policy) will not be randomised to arms containing the gentamicin-impregnated sponge.
• Purely groin incisions such as inguinal hernia repair or vascular access of the femoral vessels do not count as abdominal surgery and are not eligible to enter the trial.

The ROSSINI 2 Trial involves several types of training:

• Study-specific - this is provided by the ROSSINI 2 team during the Site Initiation Visit (SIV). It will be face-to-face whenever possible and ideally near the time of opening. Once open, further study-specific training (i.e. new staff) can be delivered via teleconference by the ROSSINI 2 team or disseminated by the PI.
• Intervention application training - this will be provided by the CI and/or surgical trainees during the SIV. Once open, intervention application training (i.e. for new staff) is to be disseminated by the PI. Training materials will be provided

 The above types of training must be completed BEFORE a site can open to recruitment.

• Wound-assessment training - this is delivered online, please click on the link 

https://bctu-redcap.bham.ac.uk/surveys/?s=DFPM7YMKRJ

The above training must be completed by anyone who will be reviewing the wound of trial participants.

The manufacturer of each product is responsible for the free provision of trial interventions to the ROSSINI 2 Trials Team. An initial supply of the interventions will be delivered to each site prior to site opening. Please get in touch with the ROSSINI 2 Trials Team to if you require additional supplies.

This study is funded by the NIHR and the Health Technology Assessment (HTA) (Grant Reference Number 16/31/123). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.

If you are a site open to ROSSINI 2 you can randomise 24 hours a day, 7 days a week. This can be done either by phone or online. The randomisation service is provided by the Centre for Healthcare Randomised Trials (CHaRT), located in the Health Services Research Unit (HSRU) at the University of Aberdeen.

Telephone Randomisation - call 0800 2802 307

You will need to know your centre/site ID code and your own unique ID code, and be required to enter these at the start of the call. This will be available from your local PI and their team, and also from the ROSSINI 2 Trial Office.

Online randomisation - visit https://w3.abdn.ac.uk/hsru/ROSSINI2

Please find below links to important ROSSINI 2 trial documents.

 ROSSINI 2 Protocol V2.0

If you experience any difficulty in accessing the protocol, please send an email to the ROSSINI 2 Trial mailbox ROSSINI2@trials.bham.ac.uk.

Will my taking part in ROSSINI 2 be kept confidential?

If you decide to take part in ROSSINI 2, we will need to collect information about you and some of this information will be your personal data. Under data protection law, we have to provide you with very specific information about what we do with your data and about your rights.

The University of Birmingham is the sponsor for this trial based in the United Kingdom. The University will use information from you and your medical records and will act as the data controller for this trial. This means that the University of Birmingham is responsible for looking after your information and using it properly.

Your rights to access, change or move your information are limited, as we need to manage your information in specific ways in order for the research to be reliable and accurate. If you withdraw from the trial, we will keep the information about you that we have already obtained. To safeguard your rights, we will use the minimum personally-identifiable information possible.

More information on how the University processes personal data can be found on the University’s website on the page ‘Data Protection – How the University Uses Your Data’ (http://www.birmingham.ac.uk/privacy/indec.aspx).

Your hospital will use your name, NHS number, date of birth and contact details to contact you about the ROSSINI 2 trial, and make sure that relevant information about the trial is recorded for your care, and to oversee the quality of the trial. Individuals from The University of Birmingham and regulatory organisations may look at your medical and research records to check the accuracy of the research trial. Your hospital will pass these details to the University of Birmingham along with the information collected from you and your medical records. The only people at the University of Birmingham who will have access to information that identifies you will be people who need to contact you to complete questionnaires or audit the data collection process. The people who analyse the information will not be able to identify you and will not be able to find out your name, NHS number or contact details. The legal justification we have under data protection law for processing your personal data is that it is necessary for our research, which is a task we carry out in the public interest. These data will not be used to make decisions about you.

Your hospital and the University of Birmingham will keep identifiable information about you from this trial for 10 years after the trial has finished.

Your GP and the other doctors involved in your clinical care will also be notified of your participation in the ROSSINI 2 trial and kept informed of your progress. Also, the research staff involved in the trial may, in the future, access electronic data from your central NHS records, for example through NHS Digital. This will provide researchers with information that is routinely gathered and stored during your visits to primary care and hospital, and will allow researchers to find out about your health after the trial has ended and the long-term effects of the treatments. By using routinely collected data we will be able to do this without needing to contact you further. In order to do this, we would need to send your name, gender, date of birth and NHS number with any request for information.

The University takes great care to ensure that personal data is handled, stored and disposed of confidentially and securely. Staff have received regular data protection training and the University has put in place organisational and technical measure so that personal data is processed in accordance with the data protection principles set out in data protection law. With regards to ROSSINI 2, information about your operation and follow-up will be sent by your doctors to the ROSSINI 2 Trial office at the Birmingham Clinical Trials Unit (BCTU), University of Birmingham on paper and/or electronically, where it will be securely stored.

The manufacturers of all the interventions for the trial will review limited information about any complications experienced by anyone in ROSSINI 2. This data will be anonymised and will not identify you.