Back to resultsROSSINI 2 - Reduction of Surgical Site Infection Using Several Novel Interventions (ROSSINI 2)
Primary Purpose
Surgical Site Infection, Surgical Wound Infection, Surgery--Complications
Status
Recruiting
Phase
Phase 3
Locations
United Kingdom
Study Type
Interventional
Intervention
2% alcoholic chlorhexidine skin prep (SKIN PREP)
Iodophor Antimicrobial Incise Drapes (DRAPE)
Gentamicin-impregnated implants/ sponges (SPONGE)
NONE (Control)
Sponsored by
About this trial
This is an interventional prevention trial for Surgical Site Infection focused on measuring SSI, Surgical Site Infection, Infection Prevention, MAMS, Multi-arm, Multi-stage, Pragmatic, Abdominal Surgery, Multicentre, RCT, Pilot, Chlorhexidine, Skin Prep, Iodophor, Drape, Gentamicin, Sponge, Surgery
Eligibility Criteria
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 a wound assessment 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.
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
- 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.
Sites / Locations
- Queen Elizabeth Hospital BirminghamRecruiting
- Countess of Chester HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm Type
Active Comparator
Active Comparator
Other
Active Comparator
Other
Active Comparator
Other
Other
Arm Label
A - NONE (Control)
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
Arm Description
Any skin preparation of the surgeon's choice may be used in the control arm apart from 2.0% Alcoholic Chlorhexidine Skin Prep. No drapes or sponges of any kind may be used.
Mechanism: A broad-spectrum antiseptic to clean and prepare the skin prior to surgery. Supplier: BD
Please note: In January 2022, following the first interim analysis, arms including intervention 2 - Iodophor-impregnated incise drape (arms C, E, G and H) were closed to recruitment. Mechanism: A thin impregnated plastic sheet applied to the prepared skin prior to incision to maintain sterility. Supplier: 3M Infection Prevention
Mechanism: Small absorbable sponges placed into the wound at the time of closure which deliver high concentrations of antibiotic locally to kill pathogens present that may go on to cause SSI. Supplier: SERB
Please note: In January 2022, following the first interim analysis, arms including intervention 2 - Iodophor-impregnated incise drape (arms C, E, G and H) were closed to recruitment. See descriptions in single arms (B & C)
See descriptions in single arms (B & D)
Please note: In January 2022, following the first interim analysis, arms including intervention 2 - Iodophor-impregnated incise drape (arms C, E, G and H) were closed to recruitment. See descriptions in single arms (C & D)
Please note: In January 2022, following the first interim analysis, arms including intervention 2 - Iodophor-impregnated incise drape (arms C, E, G and H) were closed to recruitment. See descriptions in single arms (B, C & D)
Outcomes
Primary Outcome Measures
SSI rate up to 30 days after surgery as defined according to the 2017 Centers for Disease Control (CDC) and Prevention Criteria.
The CDC definition will be used in ROSSINI 2 to identify deep incisional or superficial incisional SSIs.
Secondary Outcome Measures
30-day postoperative mortality rate (POMR).
The 30-day postoperative mortality rate (POMR) is determined as death of a patient within the first 30 postoperative days, with day of surgery taken as day 0.
30-day postoperative wound complication rate.
The 30-day postoperative complication rate is determined as the highest level Clavien-Dindo grade complication measured in the first 30 postoperative days, with day of surgery taken as day 0. Any deviation from the normal postoperative course that has an adverse effect on the patient and is not either a treatment failure or sequel, is a complication. The Clavien-Dindo classification determines the severity of a complication based on the therapeutic consequence of that complication.
Serious Adverse Events up to 30 days (wounds or intervention-related only).
The following SAEs (that are related to the use of each intervention (or the control)) should always be recorded and reported (within 24 hours) to the BCTU Trials Office as a SAE, on the
In-Theatre Form and SAE Form:
Death (related to the trial/ intervention(s))
Skin reactions
Allergic reactions
Combustion
As ROSSINI 2 is a non - CTIMP, BCTU will not be collecting Suspected Unexpected Serious Adverse Reactions (SUSARs). We will however be collecting Related and Unexpected SAEs.
A Related and Unexpected Serious Adverse Event (RUSAE) means a SAE occurring to a research participant which in the opinion of the Chief Investigator was:
'Related' that is, it resulted from the administration of any of the research procedures, and
'Unexpected' that is, the type of event is not listed in the protocol as an expected occurrence.
Length of hospital stay after surgery as measured from the date of surgery to the date of discharge.
Length of hospital stay after surgery will be a 'Time to event' outcome, this will be compared between treatment groups using standard survival analysis methods. Kaplan-Meier survival curves will be constructed for visual presentation of time-to-event comparisons. Cox proportional hazard models will be fitted to obtain adjusted treatment effects which will be expressed as hazard ratios with 95% confidence intervals.
Hospital re-admission for wound related complications within 30 days.
Hospital re-admissions for wound related complications within 30 days after surgery will be a 'Time to event' outcome, this will be compared between treatment groups using standard survival analysis methods. Kaplan-Meier survival curves will be constructed for visual presentation of time-to-event comparisons. Cox proportional hazard models will be fitted to obtain adjusted treatment effects which will be expressed as hazard ratios with 95% confidence intervals.
Occurrence of unplanned wound reopening and/or re-operations within 30 days post-operation.
Occurrence of unplanned wound reopening and/or re-operations within 30 days after surgery will be a 'Time to event' outcome, this will be compared between treatment groups using standard survival analysis methods. Kaplan-Meier survival curves will be constructed for visual presentation of time-to-event comparisons. Cox proportional hazard models will be fitted to obtain adjusted treatment effects which will be expressed as hazard ratios with 95% confidence intervals.
Health-related, preference-based quality of life
QoL will be assessed using the widely validated EuroQol EQ-5D-5L questionnaire at baseline (preoperative), as an inpatient (day 7 or at discharge if sooner) and day 30 mirroring the timings of blinded wound assessment.
Cost-effectiveness
Cost effectiveness will be assessed using the Resource Usage Form to collect patient-level health resource usage both in primary and secondary care; reported in QALYs.
Full Information
NCT ID
NCT03838575
First Posted
February 5, 2019
Last Updated
November 21, 2022
Sponsor
University of Birmingham
Collaborators
National Institute for Health Research, United Kingdom, University College, London
1. Study Identification
Unique Protocol Identification Number
NCT03838575
Brief Title
ROSSINI 2 - Reduction of Surgical Site Infection Using Several Novel Interventions
Acronym
ROSSINI 2
Official Title
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 Type
Interventional
2. Study Status
Record Verification Date
June 2022
Overall Recruitment Status
Recruiting
Study Start Date
March 1, 2019 (Actual)
Primary Completion Date
May 2023 (Anticipated)
Study Completion Date
August 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Birmingham
Collaborators
National Institute for Health Research, United Kingdom, University College, London
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
ROSSINI 2 is 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 surgery.
Detailed Description
The primary objective of ROSSINI 2 is to determine whether several specific in-theatre interventions, used alone or in combination, result in decreased rates of surgical site infection (SSI) up to 30 days post operation in adult patients undergoing abdominal surgery.
At least 60 NHS hospitals in the UK will participate in ROSSINI 2.
Approximately 6610 patients will be required to detect a 5% absolute risk reduction in the intervention arm(s) (15% to 10%; 33% relative reduction) with 85% power.
Initially, the three health technologies that were assessed versus the control arm (standard care) were:
2% alcoholic chlorhexidine skin preparation, versus any other standard skin preparation
Iodophor-impregnated incise drape, versus no drape
Gentamicin-impregnated implants/ sponge at closure, versus no implant
Please note: In January 2022, following the first interim analysis, arms including intervention 2 - Iodophor-impregnated incise drape (arms C, E, G and H) were closed to recruitment.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Surgical Site Infection, Surgical Wound Infection, Surgery--Complications, Surgery
Keywords
SSI, Surgical Site Infection, Infection Prevention, MAMS, Multi-arm, Multi-stage, Pragmatic, Abdominal Surgery, Multicentre, RCT, Pilot, Chlorhexidine, Skin Prep, Iodophor, Drape, Gentamicin, Sponge, Surgery
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
This major, multicentre, multi-arm, multi-stage (MAMS) trial with the opportunity to cease (and introduce) arms 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.
Please note: In January 2022, following the first interim analysis, arms including intervention 2 - Iodophor-impregnated incise drape (arms C, E, G and H) were closed to recruitment. This means that only 3 interventional arms (4 including the control arm) remain in the trial.
Masking
ParticipantOutcomes Assessor
Masking Description
ROSSINI 2 is a double blind trial; both the patient and outcome assessor will be blinded to the intraoperative intervention(s). It is not possible to blind the operating surgeon to the intervention allocation.
The following measures will be taken to ensure concealment of the chosen intervention(s) (blinding):
Randomisation in theatre after induction of anaesthesia
The intraoperative interventions used will not be documented in the operation notes or in the patient's notes.
The skin around the closed wound will be wiped clean using a wet sterile towel at the end of the procedure to prevent unblinding.
Clinical follow-up will be conducted by a trained surgeon or a trained member of the local research team who did not participate in the index procedure or surgery.
Allocation
Randomized
Enrollment
6610 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
A - NONE (Control)
Arm Type
Active Comparator
Arm Description
Any skin preparation of the surgeon's choice may be used in the control arm apart from 2.0% Alcoholic Chlorhexidine Skin Prep.
No drapes or sponges of any kind may be used.
Arm Title
B - SKIN PREP
Arm Type
Active Comparator
Arm Description
Mechanism: A broad-spectrum antiseptic to clean and prepare the skin prior to surgery.
Supplier: BD
Arm Title
C - DRAPE
Arm Type
Other
Arm Description
Please note: In January 2022, following the first interim analysis, arms including intervention 2 - Iodophor-impregnated incise drape (arms C, E, G and H) were closed to recruitment.
Mechanism: A thin impregnated plastic sheet applied to the prepared skin prior to incision to maintain sterility.
Supplier: 3M Infection Prevention
Arm Title
D - SPONGE
Arm Type
Active Comparator
Arm Description
Mechanism: Small absorbable sponges placed into the wound at the time of closure which deliver high concentrations of antibiotic locally to kill pathogens present that may go on to cause SSI.
Supplier: SERB
Arm Title
E - SKIN PREP and DRAPE
Arm Type
Other
Arm Description
Please note: In January 2022, following the first interim analysis, arms including intervention 2 - Iodophor-impregnated incise drape (arms C, E, G and H) were closed to recruitment.
See descriptions in single arms (B & C)
Arm Title
F - SKIN PREP and SPONGE
Arm Type
Active Comparator
Arm Description
See descriptions in single arms (B & D)
Arm Title
G - DRAPE and SPONGE
Arm Type
Other
Arm Description
Please note: In January 2022, following the first interim analysis, arms including intervention 2 - Iodophor-impregnated incise drape (arms C, E, G and H) were closed to recruitment.
See descriptions in single arms (C & D)
Arm Title
H - SKIN PREP and DRAPE and SPONGE
Arm Type
Other
Arm Description
Please note: In January 2022, following the first interim analysis, arms including intervention 2 - Iodophor-impregnated incise drape (arms C, E, G and H) were closed to recruitment.
See descriptions in single arms (B, C & D)
Intervention Type
Drug
Intervention Name(s)
2% alcoholic chlorhexidine skin prep (SKIN PREP)
Other Intervention Name(s)
Chloraprep
Intervention Description
This intervention describes the preparation of the intact skin incision site immediately prior to incision, using chlorhexidine gluconate (CHG) in an alcohol-based solution, providing durable sterilisation of the surgical field. Pre-prepared applicators will be available for use in this trial (ChloraPrep™ sticks, 2% CHG with 70% isopropyl alcohol, BD Infection Prevention).
Intervention Type
Device
Intervention Name(s)
Iodophor Antimicrobial Incise Drapes (DRAPE)
Other Intervention Name(s)
Ioban Incise Drape
Intervention Description
Please note: In January 2022, following the first interim analysis, arms including intervention 2 - Iodophor-impregnated incise drape (arms C, E, G and H) were closed to recruitment.
This intervention describes the application of a single Iodophor Antimicrobial Incise Drape to be applied topically onto the prepared and draped surgical field by sterile, gloved members of the surgical team before the surgical incision is performed. Only after the skin preparation solution has dried completely can the incise drape be applied.
Intervention Type
Device
Intervention Name(s)
Gentamicin-impregnated implants/ sponges (SPONGE)
Other Intervention Name(s)
Collatamp G
Intervention Description
This intervention describes the implantation of Gentamicin-impregnated collagen implants at the time of fascial closure. Each sponge (10 by 10 cm) contains 280mg of collagen and 130mg of gentamicin. The sponges gradually degrade and the gentamicin solution permeates into surrounding tissues to create a high local antimicrobial concentration within the surgical wound.
Intervention Type
Other
Intervention Name(s)
NONE (Control)
Intervention Description
Any skin preparation of the surgeon's choice may be used in the control arm apart from 2.0% Alcoholic Chlorhexidine Skin Prep.
No drapes or sponges of any kind may be used.
Primary Outcome Measure Information:
Title
SSI rate up to 30 days after surgery as defined according to the 2017 Centers for Disease Control (CDC) and Prevention Criteria.
Description
The CDC definition will be used in ROSSINI 2 to identify deep incisional or superficial incisional SSIs.
Time Frame
30 days post surgery
Secondary Outcome Measure Information:
Title
30-day postoperative mortality rate (POMR).
Description
The 30-day postoperative mortality rate (POMR) is determined as death of a patient within the first 30 postoperative days, with day of surgery taken as day 0.
Time Frame
Within 30 days post surgery
Title
30-day postoperative wound complication rate.
Description
The 30-day postoperative complication rate is determined as the highest level Clavien-Dindo grade complication measured in the first 30 postoperative days, with day of surgery taken as day 0. Any deviation from the normal postoperative course that has an adverse effect on the patient and is not either a treatment failure or sequel, is a complication. The Clavien-Dindo classification determines the severity of a complication based on the therapeutic consequence of that complication.
Time Frame
Within 30 days post surgery
Title
Serious Adverse Events up to 30 days (wounds or intervention-related only).
Description
The following SAEs (that are related to the use of each intervention (or the control)) should always be recorded and reported (within 24 hours) to the BCTU Trials Office as a SAE, on the
In-Theatre Form and SAE Form:
Death (related to the trial/ intervention(s))
Skin reactions
Allergic reactions
Combustion
As ROSSINI 2 is a non - CTIMP, BCTU will not be collecting Suspected Unexpected Serious Adverse Reactions (SUSARs). We will however be collecting Related and Unexpected SAEs.
A Related and Unexpected Serious Adverse Event (RUSAE) means a SAE occurring to a research participant which in the opinion of the Chief Investigator was:
'Related' that is, it resulted from the administration of any of the research procedures, and
'Unexpected' that is, the type of event is not listed in the protocol as an expected occurrence.
Time Frame
Within 30 days post surgery
Title
Length of hospital stay after surgery as measured from the date of surgery to the date of discharge.
Description
Length of hospital stay after surgery will be a 'Time to event' outcome, this will be compared between treatment groups using standard survival analysis methods. Kaplan-Meier survival curves will be constructed for visual presentation of time-to-event comparisons. Cox proportional hazard models will be fitted to obtain adjusted treatment effects which will be expressed as hazard ratios with 95% confidence intervals.
Time Frame
Measured from the date of surgery (Day 0) to the date of discharge (expected to be within 30 days.)
Title
Hospital re-admission for wound related complications within 30 days.
Description
Hospital re-admissions for wound related complications within 30 days after surgery will be a 'Time to event' outcome, this will be compared between treatment groups using standard survival analysis methods. Kaplan-Meier survival curves will be constructed for visual presentation of time-to-event comparisons. Cox proportional hazard models will be fitted to obtain adjusted treatment effects which will be expressed as hazard ratios with 95% confidence intervals.
Time Frame
Within 30 days post surgery
Title
Occurrence of unplanned wound reopening and/or re-operations within 30 days post-operation.
Description
Occurrence of unplanned wound reopening and/or re-operations within 30 days after surgery will be a 'Time to event' outcome, this will be compared between treatment groups using standard survival analysis methods. Kaplan-Meier survival curves will be constructed for visual presentation of time-to-event comparisons. Cox proportional hazard models will be fitted to obtain adjusted treatment effects which will be expressed as hazard ratios with 95% confidence intervals.
Time Frame
Within 30 days post surgery
Title
Health-related, preference-based quality of life
Description
QoL will be assessed using the widely validated EuroQol EQ-5D-5L questionnaire at baseline (preoperative), as an inpatient (day 7 or at discharge if sooner) and day 30 mirroring the timings of blinded wound assessment.
Time Frame
Baseline, Day 7, Day 30 and if applicable Ongoing SSI (Day 60, 90, 120 etc)
Title
Cost-effectiveness
Description
Cost effectiveness will be assessed using the Resource Usage Form to collect patient-level health resource usage both in primary and secondary care; reported in QALYs.
Time Frame
To complete at Day 30 and if applicable Ongoing SSI (Day 60, 90, 120 etc)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 a wound assessment 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.
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
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kayley King
Phone
00 44 121 415 8840
Email
k.king.2@bham.ac.uk
First Name & Middle Initial & Last Name or Official Title & Degree
ROSSINI 2 Mailbox
Email
rossini2@trials.bham.ac.uk
Facility Information:
Facility Name
Queen Elizabeth Hospital Birmingham
City
Birmingham
ZIP/Postal Code
B15 2GW
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Professor Pinkney
Facility Name
Countess of Chester Hospital
City
Chester
ZIP/Postal Code
CH2 1UL
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mr Vimalachandran
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
No IPD will be shared with other researchers.
Learn more about this trial
ROSSINI 2 - Reduction of Surgical Site Infection Using Several Novel Interventions
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