Condition category
Surgery
Date applied
11/02/2019
Date assigned
04/03/2019
Last edited
04/03/2019
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Around a quarter of patients undergoing abdominal operations will develop an infection of the wound. If this occurs, they will need to stay in hospital for up to double the normal length to treat the infection, and they are likely to have increased levels of pain and subsequent hernia formation as well as cosmetically inferior scars. In rare cases an SSI can be very severe and cause or contribute towards a patient’s death after surgery. SSI is also a significant problem for the NHS due to increased treatment costs and resource usage both in hospital and in the community. It is therefore a priority and a current NHS quality target to try and reduce SSI rates. There are many measures that surgeons can undertake during an operation to try to prevent SSI but very few of them have been subject to high-quality testing. This is often because trials undertaken to investigate them are too small or are not generalisable to the wider population. This trial has been carefully designed to investigate several interventions at once which makes it both cheaper and quicker than running several smaller separate trials. The aim of this study is to test whether a group of simple interventions, used alone or in combination during surgery, can reduce the chance of a patient developing a wound infection also known as a surgical site infection (SSI) after surgery on the abdomen (tummy).

Who can participate?
Patients 16 years or older, undergoing abdominal surgery of any type, both planned and unplanned, with an anticipated wound of at least 5 cm

What does the study involve?
Three in-theatre interventions are being assessed. Patients are randomly allocated to receive all, none or some of these in any combination. They are:
1. Chlorhexidine 2% alcohol skin preparation - a strong cleaning solution to cleanse and sterilise the skin before surgery. This will be compared against any other standard skin preparation that a surgeon may normally use.
2. An Iodophor-impregnated incise drape - a very thin plastic sheet stuck onto the skin before surgery and thought to prevent infection by trapping any bacteria left on the skin after preparation, as well as preventing new bacteria ingress. This will be compared against no drape.
3. Gentamicin-impregnated collagen implant/sponge - small absorbable sponges placed in the wound at the end of the operation that slowly disintegrate and deliver antibiotics locally to try and kill any bacteria present that may go on to cause an SSI. This will be compared against no implant.
It is possible that these interventions might have a cumulative effect. This trial will both test each intervention and look in a rational fashion at how they might work together.

What are the possible benefits and risks of participating?
All interventions have the potential benefit of reducing the chances of developing an infection in the wound. The alternative possibility is that the interventions will not be of any benefit at all. To the best of the researchers' knowledge, none of the included interventions will increase the risk of getting a SSI and do not add any further risk to the operation itself. The skin preparation takes about 2-3 minutes to apply at the start of the operation as does the drape. The sponges are left in the wound at the end of the operation and take about 1-2 minutes to insert. As with any intervention, there is a rare risk of allergy. If patients have a documented or suspected allergy to any of the interventions (or its parts) we will not offer the patient that intervention but they can still participate in the trial.

Where is the study run from?
The study is coordinated from the University of Birmingham, Birmingham Clinical Trials Unit (BCTU).

When is the study starting and how long is it expected to run for?
March 2018 to February 2022

Who is funding the study?
National Institute for Health Research (NIHR) (UK)

Who is the main contact?
Kayley King
k.king.2@bham.ac.uk

Trial website

Contact information

Type

Public

Primary contact

Miss Kayley King

ORCID ID

Contact details

Senior Trial Manager
Birmingham Clinical Trials Unit (BCTU)
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom
+44 (0)121 415 8840
k.king.2@bham.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

39722

Study information

Scientific title

ROSSINI 2: A Phase III, multi-arm, multi-stage (MAMS) pragmatic, blinded (patient and outcome assessor) multicentre, randomised controlled trial (RCT) with an internal pilot, to evaluate the use of three in-theatre interventions, alone or in combination, to reduce SSI rates in patients undergoing abdominal surgery.

Acronym

ROSSINI 2

Study hypothesis

Surgical site infection (SSI) is a significant problem for patients and the health service, but is potentially preventable. Up to 25% of patients undergoing abdominal operations will develop an SSI. 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. Patients who develop SSIs have higher rates of pain and discomfort, with an increased risk of death following their operation.

The aim of ROSSINI 2 is to see whether three new in-theatre interventions, alone or in combination, reduce the rate of SSI.

Ethics approval

Approved 29/01/2019, Wales REC 6, Fourth floor, Institute of Life Science 2, Swansea University, Singleton Park, SA2 8PP, Tel: +44 (0)1792 606334, Email: penny.beresford@wales.nhs.uk, ref: 19/WA/0019

Study design

Randomised; Interventional; Design type: Prevention, Drug, Device, Surgery

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

Colorectal surgery

Intervention

This multicentre, multi-arm, multi-stage, randomised clinical trial, will assess three separate in-theatre interventions used alone or in combination.

There will be a secure online randomisation system (available at https://w3.abdn.ac.uk/hsru/ROSSINI2) and an automated telephone randomisation system (available at 0800 2802 307) both managed by a 3rd party (The Centre for Healthcare Randomised Trials (CHaRT) at The Institute of Applied Health Sciences at University of Aberdeen). Both systems will be available 24 hours a day, 7 days a week.

Participants will be randomised at the level of the individual in a 2:1 (control:research) ratio to either control or one of the treatment groups. There will initially be seven possible treatment arms and one control arm to which a patient can be randomised.

A minimisation algorithm will be used within the online randomisation system to ensure balance in the treatment allocation over the following variables:
1. Centre
2. Urgency (planned, unplanned)
3. Predicted contamination (clean, clean-contaminated, contaminated, dirty)
4. Stoma (yes – existing, yes – likely to be created during procedure, no - unlikely to be created during procedure)

The interventions include a skin preparation solution (2% alcoholic chlorhexadine skin prep) that is applied to the skin before starting surgery, a skin drape (Iodophor-impregnated incise drape) - a thin impregnated plastic sheet applied to the skin before making the incision, and a sponge (gentamicin impregnated implant), which is an implant that contains antibiotics that is placed into the wound before closure.

Participants are randomised into the following arms:
A – Control (none)
B – Skin prep
C – Drape
D – Sponge
E – Skin prep and drape
F – Skin prep and sponge
G – Drape and sponge
H – Skin prep and drape and sponge

Each participant will undergo randomisation at time of surgery (Day 0) and will be expected to participate in ROSSINI 2 until their Day 30 Wound Assessment. Any patients who have an ongoing wound infection at 30-days postoperatively will continue to have ongoing active follow-up every 30 days until resolution to capture health economic and resource use data.

Intervention type

Procedure/Surgery

Phase

Drug names

Primary outcome measure

The SSI rate up to 30 days after surgery as defined according to the 2017 Centers for Disease Control (CDC) and Prevention criteria.
The following CDC definition will be used to identify deep incisional or superficial incisional SSIs:
1. The infection must occur within 30-days of the index operation
AND
2. The infection must involve the skin, subcutaneous, muscular or fascial layers of the incision
AND
3. The patient must have at least one of the following:
3.1. Purulent drainage from the incision
OR
3.2. Wound opened spontaneously or deliberately by a clinician
o AND the patient has at least one of: pain or tenderness; localised swelling; erythema or heat; fever (>38°C).
OR
3.3. Organisms are cultured from a culture taken from the wound using an aseptic technique
OR
3.4. Diagnosis of SSI by a clinician or on imaging

Secondary outcome measures

1. 30-day postoperative mortality rate (POMR)
2. 30-day postoperative complication rate, assessed using Clavien-Dindo classification
3. Serious Adverse Events up to 30 days
4. Length of hospital stay after surgery as measured from the date of surgery to the date of discharge
5. Hospital re-admission for wound-related complications within 30 days
6. Occurrence of unplanned wound reopening and/or re-operations within 30 days post-operation
7. Preference-based QoL measure (EQ-5D-5L) at baseline, Day 7 (or discharge) and Day 30
8. Cost-effectiveness, measured using health utility questionnaire at Day 30 and ‘Ongoing SSI’ (Day 60, Day 90 etc)

Overall trial start date

01/03/2018

Overall trial end date

28/02/2022

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Patients undergoing colorectal, hepatobiliary, upper GI, urological, vascular, or gynaecological operations
2. Patients undergoing abdominal operations (open or laparoscopic extraction site) with a planned incision of at least 5 cm
3. Patients aged 16 years or older
4. Patients able and willing to give written informed consent
5. All contamination strata, including clean, clean-contaminated, contaminated or dirty surgery
6. Patients undergoing planned (elective or expedited) or unplanned (emergency) surgery

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 6610; UK Sample Size: 6610

Participant exclusion criteria

1. Previous laparotomy within 3 months prior to randomisation
2. 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
3. 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

Recruitment start date

01/03/2019

Recruitment end date

01/10/2021

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Queen Elizabeth Hospital Birmingham (lead site)
Mindelsohn Way Edgbaston
Birmingham
B15 2TH
United Kingdom

Sponsor information

Organisation

University of Birmingham

Sponsor details

c/o Dr Birgit Whitman
Room 117
Aston Webb Building
Edgbaston
Birmingham
B15 2TT
United Kingdom
+44 (0)121 415 8011
researchgovernance@contacts.bham.ac.uk

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

NIHR Evaluation, Trials and Studies Co-ordinating Centre (NETSCC); Grant Codes: 16/31/123

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Patient and public involvement
There are two named patient representatives on the trial design and management committee, ensuring that patients and their interests remain central. A patient focus group has also reviewed and optimised all patient-facing documentation such as information leaflets and consent forms.

The protocol will be published in the near future in a peer reviewed journal. The SAP will be available online via our trial website in due course.

Dissemination
The results will be used to advise surgeons how to best reduce the risk of surgical site infections. This may include recommending against the use of the above interventions if some or all are found not to work or be cost-effective. Results will be presented and published locally, nationally and internationally. The patient group will help create lay summaries of our findings for dissemination to trial participants and the wider population.

Planned publications will include:
1. Presentations – at national and international meetings including Association of Surgeons of Great Britain and Ireland, the Association of Coloproctology of Great Britain and Ireland and the European Society of Coloproctology etc.
2. Publications – the researchers will aim for several high impact factor peer-reviewed publications from this project, such as The Lancet, British Medical Journal and Annals of Surgery.
3. National and European guidelines – the findings will be incorporated into new and existing guidelines for the prevention of SSI to allow further dissemination to commissioners and clinicians. Examples will include NICE CG74, SIGN, and the World Health Organisation SSI guidelines.

IPD sharing statement
The datasets generated during and/or analysed during the current study are/will be available upon request - exact details not yet known.

Intention to publish date

28/02/2023

Participant level data

Available on request

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes