ROSSINI 2 - Reduction of Surgical Site Infection Using Several Novel Interventions

Phase 3

• Conditions: Surgical Wound Infection; Surgery--Complications; Surgery; Surgical Site Infection
• Interventions: Drug: 2% alcoholic chlorhexidine skin prep (SKIN PREP); Device: Iodophor Antimicrobial Incise Drapes (DRAPE); Other: NONE (Control); Device: Gentamicin-impregnated implants/ sponges (SPONGE)

• Registration Number: NCT03838575
• Lead Sponsor: University of Birmingham

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:

1. 2% alcoholic chlorhexidine skin preparation, versus any other standard skin preparation

2. Iodophor-impregnated incise drape, versus no drape

3. 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.

Study Timeline

• Study First Submitted: 2019-02-05
• Study First Submitted QC: 2019-02-11
• Study First Posted: 2019-02-12
• Study Start: 2019-03-01
• Status Verified: 2022-06
• Last Update Submitted: 2022-11-21
• Last Update Posted: 2022-11-28
• Primary Completion: 2023-05
• Study Completion: 2023-08

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 6610

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.

Read More

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.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
E - SKIN PREP and DRAPE	2% alcoholic chlorhexidine skin prep (SKIN PREP)	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)
H - SKIN PREP and DRAPE and SPONGE	2% alcoholic chlorhexidine skin prep (SKIN PREP)	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)
B - SKIN PREP	2% alcoholic chlorhexidine skin prep (SKIN PREP)	Mechanism: A broad-spectrum antiseptic to clean and prepare the skin prior to surgery. Supplier: BD
C - DRAPE	Iodophor Antimicrobial Incise Drapes (DRAPE)	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
E - SKIN PREP and DRAPE	Iodophor Antimicrobial Incise Drapes (DRAPE)	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)
A - NONE (Control)	NONE (Control)	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.
G - DRAPE and SPONGE	Iodophor Antimicrobial Incise Drapes (DRAPE)	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)
G - DRAPE and SPONGE	Gentamicin-impregnated implants/ sponges (SPONGE)	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)
H - SKIN PREP and DRAPE and SPONGE	Gentamicin-impregnated implants/ sponges (SPONGE)	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)
D - SPONGE	Gentamicin-impregnated implants/ sponges (SPONGE)	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
F - SKIN PREP and SPONGE	Gentamicin-impregnated implants/ sponges (SPONGE)	See descriptions in single arms (B \& D)
H - SKIN PREP and DRAPE and SPONGE	Iodophor Antimicrobial Incise Drapes (DRAPE)	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)
F - SKIN PREP and SPONGE	2% alcoholic chlorhexidine skin prep (SKIN PREP)	See descriptions in single arms (B \& D)

Primary Outcome Measures

Name	Time	Method
SSI rate up to 30 days after surgery as defined according to the 2017 Centers for Disease Control (CDC) and Prevention Criteria.	30 days post surgery	The CDC definition will be used in ROSSINI 2 to identify deep incisional or superficial incisional SSIs.

Secondary Outcome Measures

Name	Time	Method
30-day postoperative mortality rate (POMR).	Within 30 days post surgery	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.
Health-related, preference-based quality of life	Baseline, Day 7, Day 30 and if applicable Ongoing SSI (Day 60, 90, 120 etc)	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.
Hospital re-admission for wound related complications within 30 days.	Within 30 days post surgery	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.	Within 30 days post surgery	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.
Cost-effectiveness	To complete at Day 30 and if applicable Ongoing SSI (Day 60, 90, 120 etc)	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.
30-day postoperative wound complication rate.	Within 30 days post surgery	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.
Length of hospital stay after surgery as measured from the date of surgery to the date of discharge.	Measured from the date of surgery (Day 0) to the date of discharge (expected to be within 30 days.)	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.
Serious Adverse Events up to 30 days (wounds or intervention-related only).	Within 30 days post surgery	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.

Trial Locations

Locations (2)

Queen Elizabeth Hospital Birmingham; 🇬🇧 Birmingham, United Kingdom

Countess of Chester Hospital; 🇬🇧 Chester, United Kingdom