Reduction Of Surgical Site Infection using several Novel Interventions
| ISRCTN | ISRCTN78305317 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN78305317 |
| IRAS number | 247285 |
| ClinicalTrials.gov number | NCT03838575 |
| Secondary identifying numbers | CPMS 39722, IRAS 247285 |
- Submission date
- 11/02/2019
- Registration date
- 04/03/2019
- Last edited
- 03/03/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Surgery
Plain English summary of protocol
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 October 2026
Who is funding the study?
National Institute for Health Research (NIHR) (UK)
Who is the main contact?
Dr Zerin Alimajstorovic, z.alimajstorovic@bham.ac.uk
Contact information
Public
Birmingham Clinical Trials Unit (BCTU)
Public Health Building
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom
 ORCID ID |
0000-0001-5622-8301 |
|---|---|
| Phone | +44 (0)121 415 8840 |
| z.alimajstorovic@bham.ac.uk |
Study information
| Study design | Multi-arm, multi-stage (MAMS), pragmatic, multicentre, randomized controlled trial, with an internal pilot, exploring the use of several specific in-theatre interventions, used alone or in combination, to reduce the rates of SSIs. A non-factorial design with allocations to various combinations of the trial interventions to be used during the same operation. (Platform) |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Prevention |
| Participant information sheet | ISRCTN16682024_PIS_03Sep2020.pdf |
| 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 several in-theatre interventions used alone or in combination, to reduce SSI rates in patients undergoing abdominal surgery |
| Study acronym | ROSSINI 2 |
| Study objectives | Current study hypothesis as of 24/03/2023: 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. There is a significant health need for research to address the problem of SSI, with benefit for both patients and the NHS. SSI is associated with considerable morbidity, a reduction in quality of life and increased healthcare costs, and places a significant burden on healthcare systems and individuals. Patients who develop SSIs have higher rates of pain and discomfort, with an increased risk of death following their operation. Preventing SSI is a complex process which is affected by interventions throughout the surgical care pathway. SSI reduction measures when bundled, or poorly implemented can be ineffective or even increase SSI risk. A large proportion of SSIs are known to be caused by wound contamination by endogenous bacteria from the patient’s skin, or cross contamination from mucous membranes, hollow viscera, free pus or bowel content. Unfortunately, clinical studies exploring the efficacy of many of these interventions are often underpowered or poorly designed, or used in low risk groups leaving uncertainty if they are clinically and cost-effective. ROSSINI 2 aims to study simple biologically plausible interventions that may decrease SSI rates after abdominal surgery, but currently lack evidence in controlled studies. The aim of ROSSINI 2 is to determine whether several novel in-theatre interventions, used alone or in combination, result in decreased rates of SSI up to 30 days post operation in adult patient undergoing abdominal surgery. Previous 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(s) | Approved 29/01/2019, Wales REC 6, Fourth floor, Institute of Life Science 2, Swansea University, Singleton Park, SA2 8PP, UK; +44 (0)1792 606334; penny.beresford@wales.nhs.uk, ref: 19/WA/0019 |
| Health condition(s) or problem(s) studied | Patients undergoing abdominal surgery for any indication |
| Intervention | Current interventions as of 03/03/2025: The current interventions are: A: None (Control) I. Change of Gloves and Instruments immediately before fascial closure vs standard practice. J: Dialkylcarbamoyl chloride (DACC) impregnated dressing. K: Change of Gloves and Instruments immediately before fascial closure and Dialkylcarbamoyl chloride (DACC) impregnated dressing. _____ Previous interventions as of 24/03/2023: This multicentre, multi-arm, multi-stage, randomised clinical trial, will originally 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 +44 (0)800 2802 307) both managed by a third 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 intervention arms. There will initially be seven possible intervention 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: - 2% Alcoholic Chlorhexidine SKIN PREP - Iodophor-impregnated incise DRAPE - A Gentamicin-impregnated SPONGE During Stage 1 and Stage 2 of ROSSINI 2, 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 UPDATE (2021) : On 15/12/2021, the results of the first interim analysis (end of Stage 2) were presented and reviewed by the independent DMC. They made the recommendation to drop the intervention arms containing Intervention 2, Iodophor-impregnated incise DRAPE. The DMC recommendations were discussed by the ROSSINI 2 TMG, independent TSC, Sponsor and Funder at a meeting on 07/01/2022. Following this meeting, it was agreed that the following arms containing Intervention 2, Iodophor-impregnated incise DRAPE, would close to recruitment: C - DRAPE E - SKIN PREP & DRAPE G - DRAPE & SPONGE H - SKIN PREP & DRAPE & SPONGE UPDATE (2023): On 25/01/2023, the results of the second interim analysis (end of Stage 3) were presented and reviewed by the independent DMC. They made the recommendation to drop the intervention arms containing Intervention 3, Gentamicin-impregnated SPONGE. The DMC recommendations were discussed by the independent TSC, the ROSSINI 2 TMG and Sponsor at a meeting on 31/01/2023. Following the meeting, it was agreed that the following arms containing Intervention 3, Gentamicin-impregnated SPONGE, would close to recruitment: D - SPONGE F - SKIN PREP & 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. Previous interventions: 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 | Mixed |
| 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 | Current secondary outcome measures as of 24/03/2023: 1. 30-day postoperative mortality rate (POMR) 2. 30-day postoperative wound complication rate, assessed using Clavien-Dindo classification 3. Serious Adverse Events up to 30 days (wound or intervention-related only) 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) Previous 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 study start date | 01/03/2018 |
| Completion date | 31/10/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 16 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 6610; UK Sample Size: 6610 |
| Key inclusion criteria | Current inclusion criteria as of 24/03/2023: 1. Patients undergoing an abdominal operation, these include 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 undergo a wound assessment at day 30-37 after surgery 5. Patients able and willing to give written informed consent 6. All contamination strata, including clean, clean-contaminated, contaminated or dirty surgery 7. Patients undergoing planned (elective or expedited) or unplanned (emergency) surgery _____ Previous 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 |
| Key exclusion criteria | Current exclusion criteria as of 03/03/2025: 1. Previous laparotomy within 3 months prior to randomisation 2. Operations where the wound is not anticipated to be closed primarily _____ Previous 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 |
| Date of first enrolment | 07/03/2019 |
| Date of final enrolment | 30/06/2026 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Edgbaston
Birmingham
B15 2TH
United Kingdom
Sponsor information
University/education
c/o Dr Birgit Whitman
Room 117, Aston Webb Building
Edgbaston
Birmingham
B15 2TT
England
United Kingdom
| Phone | +44 (0)121 415 8011 |
|---|---|
| researchgovernance@contacts.bham.ac.uk | |
"ROR" |
https://ror.org/03angcq70 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- NIHR Health Technology Assessment Programme, HTA
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 30/05/2024 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| 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 plan | The datasets generated during and/or analysed during the current study are/will be available upon request - exact details not yet known. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | version 1.0 | 03/09/2020 | 04/09/2020 | No | Yes |
| Protocol file | version 1.0 | 02/12/2018 | 04/09/2020 | No | No |
| Protocol file | version 2.0 | 18/07/2020 | 04/09/2020 | No | No |
| Participant information sheet | version 2.0 | 24/01/2019 | 26/04/2023 | No | Yes |
| Participant information sheet | version 3.0 | 18/07/2020 | 26/04/2023 | No | Yes |
| Participant information sheet | version 4.0 | 12/07/2022 | 26/04/2023 | No | Yes |
| Participant information sheet | version 5.0 | 24/02/2023 | 26/04/2023 | No | Yes |
| Protocol file | version 3.0 | 12/07/2022 | 26/04/2023 | No | No |
| Protocol file | version 4.0 | 24/02/2023 | 26/04/2023 | No | No |
| HRA research summary | 28/06/2023 | No | No |
Additional files
- ISRCTN78305317_PROTOCOL_V1.0 02Dec2018.pdf
- ISRCTN78305317_PROTOCOL_V2.0_18Jul2020.pdf
- ISRCTN16682024_PIS_03Sep2020.pdf
- ISRCTN78305317 ROSSINI 2 Protocol V3.0 12Jul2022.pdf
- ISRCTN78305317 ROSSINI 2 Protocol V4.0 24.02.2023.pdf
- ISRCTN78305317 ROSSINI 2 PIS V2.0 24.01.2019.pdf
- ISRCTN78305317 ROSSINI 2 PIS V3.0 18.07.2020.pdf
- ISRCTN78305317 ROSSINI 2 PIS V4.0 12.07.2022.pdf
- ISRCTN78305317 ROSSINI 2 PIS V5.0 24.02.2023.pdf
Editorial Notes
03/03/2025: The following changes were made to the trial record:
1. The overall end date was changed from 29/02/2024 to 31/10/2026.
2. The interventions were changed.
3. The exclusion criteria were changed.
4. The recruitment end date was changed from 29/02/2024 to 30/06/2026.
28/02/2025: Contact details updated.
26/04/2023: The following changes were made to the trial record:
1. Uploaded protocols (v3.0, v4.0) (not peer-reviewed) as additional files.
2. Participant information sheet v2.0, v3.0, v4.0, v5.0 were uploaded as additional files.
3. The recruitment end date was changed from 31/03/2023 to 29/02/2024.
4. The IRAS number was added.
24/03/2023: The following changes were made to the trial record:
1. The scientific title was changed from '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.' to '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 several in-theatre interventions used alone or in combination, to reduce SSI rates in patients undergoing abdominal surgery'.
2. The study hypothesis, interventions, secondary outcome measures, and inclusion criteria were updated.
3. The study design was changed from 'Randomized; Interventional; Design type: Prevention, Drug, Device, Surgery' to 'Multi-arm, multi-stage (MAMS), pragmatic, multicentre, randomized controlled trial, with an internal pilot, exploring the use of several specific in-theatre interventions, used alone or in combination, to reduce the rates of SSIs. A non-factorial design with allocations to various combinations of the trial interventions to be used during the same operation. (Platform)'.
4. The overall trial end date was changed from 30/05/2023 to 29/02/2024.
5. The condition was changed from 'Colorectal surgery' to 'Patients undergoing abdominal surgery for any indication'.
12/10/2021: The following changes were made to the trial record:
1. The recruitment end date was changed from 01/10/2021 to 31/03/2023.
2. The overall end date was changed from 28/02/2022 to 30/05/2023.
3. The intention to publish date was changed from 28/02/2022 to 30/05/2024.
4. The plain English summary was updated to reflect these changes.
04/09/2020: The following changes were made to the trial record:
1. The overall end date was changed from 30/09/2020 to 28/02/2022.
2. The intention to publish date was changed from 30/09/2020 to 28/02/2022.
3. Uploaded protocols (not peer reviewed) Version 1.0 02 December 2018 and Version 2.0 18 July 2020.
4. The participant information sheet was uploaded as an additional file.
11/08/2020: Recruitment to this study is no longer paused.
09/06/2020: The following changes were made to the trial record:
1. The overall end date was changed from 28/02/2022 to 30/09/2020.
2. The intention to publish date was changed from 28/02/2023 to 30/09/2020.
15/04/2020: Due to current public health guidance, recruitment for this study has been paused.
21/10/2019: The following changes were made to the trial record:
1. The recruitment start date was changed from 01/03/2019 to 07/03/2019.
2. ClinicalTrials.gov number and trial website added.
11/02/2019: Trial's existence confirmed by the NIHR.
