<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03838575</url>
  </required_header>
  <id_info>
    <org_study_id>RG_18-186</org_study_id>
    <nct_id>NCT03838575</nct_id>
  </id_info>
  <brief_title>ROSSINI 2 - Reduction of Surgical Site Infection Using Several Novel Interventions</brief_title>
  <acronym>ROSSINI 2</acronym>
  <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.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Birmingham</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute for Health Research, United Kingdom</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University College, London</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Birmingham</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      ROSSINI 2 is a phase III, multi-arm, multi-stage (MAMS) pragmatic, blinded (patient and&#xD;
      outcome assessor), multicentre, randomised controlled trial (RCT) with an internal pilot, to&#xD;
      evaluate the use of several in-theatre interventions, used alone or in combination, to reduce&#xD;
      SSI rates in patients undergoing surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary objective of ROSSINI 2 is to determine whether several specific in-theatre&#xD;
      interventions, used alone or in combination, result in decreased rates of surgical site&#xD;
      infection (SSI) up to 30 days post operation in adult patients undergoing abdominal surgery.&#xD;
&#xD;
      At least 60 NHS hospitals in the UK will participate in ROSSINI 2.&#xD;
&#xD;
      Approximately 6610 patients will be required to detect a 5% absolute risk reduction in the&#xD;
      intervention arm(s) (15% to 10%; 33% relative reduction) with 85% power.&#xD;
&#xD;
      Initially, the three health technologies that were assessed versus the control arm (standard&#xD;
      care) were:&#xD;
&#xD;
        1. 2% alcoholic chlorhexidine skin preparation, versus any other standard skin preparation&#xD;
&#xD;
        2. Iodophor-impregnated incise drape, versus no drape&#xD;
&#xD;
        3. Gentamicin-impregnated implants/ sponge at closure, versus no implant&#xD;
&#xD;
      Please note: In January 2022, following the first interim analysis, arms including&#xD;
      intervention 2 - Iodophor-impregnated incise drape (arms C, E, G and H) were closed to&#xD;
      recruitment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 1, 2019</start_date>
  <completion_date type="Anticipated">August 2023</completion_date>
  <primary_completion_date type="Anticipated">May 2023</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_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.&#xD;
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.</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
    <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.&#xD;
The following measures will be taken to ensure concealment of the chosen intervention(s) (blinding):&#xD;
Randomisation in theatre after induction of anaesthesia&#xD;
The intraoperative interventions used will not be documented in the operation notes or in the patient's notes.&#xD;
The skin around the closed wound will be wiped clean using a wet sterile towel at the end of the procedure to prevent unblinding.&#xD;
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.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>SSI rate up to 30 days after surgery as defined according to the 2017 Centers for Disease Control (CDC) and Prevention Criteria.</measure>
    <time_frame>30 days post surgery</time_frame>
    <description>The CDC definition will be used in ROSSINI 2 to identify deep incisional or superficial incisional SSIs.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>30-day postoperative mortality rate (POMR).</measure>
    <time_frame>Within 30 days post surgery</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>30-day postoperative wound complication rate.</measure>
    <time_frame>Within 30 days post surgery</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serious Adverse Events up to 30 days (wounds or intervention-related only).</measure>
    <time_frame>Within 30 days post surgery</time_frame>
    <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&#xD;
In-Theatre Form and SAE Form:&#xD;
Death (related to the trial/ intervention(s))&#xD;
Skin reactions&#xD;
Allergic reactions&#xD;
Combustion&#xD;
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.&#xD;
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:&#xD;
'Related' that is, it resulted from the administration of any of the research procedures, and&#xD;
'Unexpected' that is, the type of event is not listed in the protocol as an expected occurrence.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of hospital stay after surgery as measured from the date of surgery to the date of discharge.</measure>
    <time_frame>Measured from the date of surgery (Day 0) to the date of discharge (expected to be within 30 days.)</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital re-admission for wound related complications within 30 days.</measure>
    <time_frame>Within 30 days post surgery</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of unplanned wound reopening and/or re-operations within 30 days post-operation.</measure>
    <time_frame>Within 30 days post surgery</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-related, preference-based quality of life</measure>
    <time_frame>Baseline, Day 7, Day 30 and if applicable Ongoing SSI (Day 60, 90, 120 etc)</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cost-effectiveness</measure>
    <time_frame>To complete at Day 30 and if applicable Ongoing SSI (Day 60, 90, 120 etc)</time_frame>
    <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.</description>
  </secondary_outcome>
  <number_of_arms>8</number_of_arms>
  <enrollment type="Anticipated">6610</enrollment>
  <condition>Surgical Site Infection</condition>
  <condition>Surgical Wound Infection</condition>
  <condition>Surgery--Complications</condition>
  <condition>Surgery</condition>
  <arm_group>
    <arm_group_label>A - NONE (Control)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Any skin preparation of the surgeon's choice may be used in the control arm apart from 2.0% Alcoholic Chlorhexidine Skin Prep.&#xD;
No drapes or sponges of any kind may be used.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>B - SKIN PREP</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Mechanism: A broad-spectrum antiseptic to clean and prepare the skin prior to surgery.&#xD;
Supplier: BD</description>
  </arm_group>
  <arm_group>
    <arm_group_label>C - DRAPE</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <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.&#xD;
Mechanism: A thin impregnated plastic sheet applied to the prepared skin prior to incision to maintain sterility.&#xD;
Supplier: 3M Infection Prevention</description>
  </arm_group>
  <arm_group>
    <arm_group_label>D - SPONGE</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <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.&#xD;
Supplier: SERB</description>
  </arm_group>
  <arm_group>
    <arm_group_label>E - SKIN PREP and DRAPE</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <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.&#xD;
See descriptions in single arms (B &amp; C)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>F - SKIN PREP and SPONGE</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>See descriptions in single arms (B &amp; D)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>G - DRAPE and SPONGE</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <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.&#xD;
See descriptions in single arms (C &amp; D)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>H - SKIN PREP and DRAPE and SPONGE</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <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.&#xD;
See descriptions in single arms (B, C &amp; D)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>2% alcoholic chlorhexidine skin prep (SKIN PREP)</intervention_name>
    <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).</description>
    <arm_group_label>B - SKIN PREP</arm_group_label>
    <arm_group_label>E - SKIN PREP and DRAPE</arm_group_label>
    <arm_group_label>F - SKIN PREP and SPONGE</arm_group_label>
    <arm_group_label>H - SKIN PREP and DRAPE and SPONGE</arm_group_label>
    <other_name>Chloraprep</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Iodophor Antimicrobial Incise Drapes (DRAPE)</intervention_name>
    <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.&#xD;
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.</description>
    <arm_group_label>C - DRAPE</arm_group_label>
    <arm_group_label>E - SKIN PREP and DRAPE</arm_group_label>
    <arm_group_label>G - DRAPE and SPONGE</arm_group_label>
    <arm_group_label>H - SKIN PREP and DRAPE and SPONGE</arm_group_label>
    <other_name>Ioban Incise Drape</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Gentamicin-impregnated implants/ sponges (SPONGE)</intervention_name>
    <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.</description>
    <arm_group_label>D - SPONGE</arm_group_label>
    <arm_group_label>F - SKIN PREP and SPONGE</arm_group_label>
    <arm_group_label>G - DRAPE and SPONGE</arm_group_label>
    <arm_group_label>H - SKIN PREP and DRAPE and SPONGE</arm_group_label>
    <other_name>Collatamp G</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>NONE (Control)</intervention_name>
    <description>Any skin preparation of the surgeon's choice may be used in the control arm apart from 2.0% Alcoholic Chlorhexidine Skin Prep.&#xD;
No drapes or sponges of any kind may be used.</description>
    <arm_group_label>A - NONE (Control)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients undergoing colorectal, hepatobiliary, upper GI, urological, vascular, or&#xD;
             gynaecological operations&#xD;
&#xD;
          -  Patients undergoing abdominal operations (open or laparoscopic extraction site) with a&#xD;
             planned incision of at least 5cm.&#xD;
&#xD;
          -  Patients aged 16 years or older&#xD;
&#xD;
          -  Patients able and willing to undergo a wound assessment at day 30-37 after surgery&#xD;
&#xD;
          -  Patients able and willing to give written informed consent&#xD;
&#xD;
          -  All contamination strata, including clean, clean-contaminated, contaminated or dirty&#xD;
             surgery.&#xD;
&#xD;
          -  Patients undergoing planned (elective or expedited) or unplanned (emergency) surgery.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous laparotomy within 3 months prior to randomisation&#xD;
&#xD;
          -  Known to be pregnant or currently breast feeding&#xD;
&#xD;
          -  Operations where the wound is not anticipated to be closed primarily&#xD;
&#xD;
          -  Patients with a new or documented allergy/ intolerance to any of the study&#xD;
             interventions (chlorhexidine, iodine, collagen or gentamicin) will not be randomised&#xD;
             to an arm containing this intervention, but will still be eligible for recruitment to&#xD;
             other arms of the study.&#xD;
&#xD;
          -  Patients with end-stage renal failure where gentamicin administration would otherwise&#xD;
             be contra-indicated (according to local policy) will not be randomised to arms&#xD;
             containing the gentamicin-impregnated sponge.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>16 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Kayley King</last_name>
    <phone>00 44 121 415 8840</phone>
    <email>k.king.2@bham.ac.uk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>ROSSINI 2 Mailbox</last_name>
    <email>rossini2@trials.bham.ac.uk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Queen Elizabeth Hospital Birmingham</name>
      <address>
        <city>Birmingham</city>
        <zip>B15 2GW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Professor Pinkney</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Countess of Chester Hospital</name>
      <address>
        <city>Chester</city>
        <zip>CH2 1UL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mr Vimalachandran</last_name>
    </contact>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>February 5, 2019</study_first_submitted>
  <study_first_submitted_qc>February 11, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 12, 2019</study_first_posted>
  <last_update_submitted>November 21, 2022</last_update_submitted>
  <last_update_submitted_qc>November 21, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 28, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>SSI</keyword>
  <keyword>Surgical Site Infection</keyword>
  <keyword>Infection Prevention</keyword>
  <keyword>MAMS</keyword>
  <keyword>Multi-arm, Multi-stage</keyword>
  <keyword>Pragmatic</keyword>
  <keyword>Abdominal Surgery</keyword>
  <keyword>Multicentre</keyword>
  <keyword>RCT</keyword>
  <keyword>Pilot</keyword>
  <keyword>Chlorhexidine</keyword>
  <keyword>Skin Prep</keyword>
  <keyword>Iodophor</keyword>
  <keyword>Drape</keyword>
  <keyword>Gentamicin</keyword>
  <keyword>Sponge</keyword>
  <keyword>Surgery</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>Surgical Wound Infection</mesh_term>
    <mesh_term>Wound Infection</mesh_term>
    <mesh_term>Surgical Wound</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Chlorhexidine</mesh_term>
    <mesh_term>Gentamicins</mesh_term>
    <mesh_term>Anti-Infective Agents</mesh_term>
    <mesh_term>Anti-Bacterial Agents</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>No IPD will be shared with other researchers.</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>July 12, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/75/NCT03838575/Prot_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03838575
org study id: RG_18-186
nct id: NCT03838575
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
intervention 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.
primary purpose: Prevention
masking: Double (Participant, Outcomes 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.
measure: SSI rate up to 30 days after surgery as defined according to the 2017 Centers for Disease Control (CDC) and Prevention Criteria.
time frame: 30 days post surgery
description: The CDC definition will be used in ROSSINI 2 to identify deep incisional or superficial incisional SSIs.
measure: 30-day postoperative mortality rate (POMR).
time frame: Within 30 days post surgery
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.
measure: 30-day postoperative wound complication rate.
time frame: Within 30 days post surgery
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.
measure: Serious Adverse Events up to 30 days (wounds or intervention-related only).
time frame: Within 30 days post surgery
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.
measure: Length of hospital stay after surgery as measured from the date of surgery to the date of discharge.
time frame: Measured from the date of surgery (Day 0) to the date of discharge (expected to be within 30 days.)
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.
measure: Hospital re-admission for wound related complications within 30 days.
time frame: Within 30 days post surgery
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.
measure: Occurrence of unplanned wound reopening and/or re-operations within 30 days post-operation.
time frame: Within 30 days post surgery
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.
measure: Health-related, preference-based quality of life
time frame: Baseline, Day 7, Day 30 and if applicable Ongoing SSI (Day 60, 90, 120 etc)
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.
measure: Cost-effectiveness
time frame: To complete at Day 30 and if applicable Ongoing SSI (Day 60, 90, 120 etc)
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.
arm group label: A - NONE (Control)
arm group type: Active Comparator
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 group label: B - SKIN PREP
arm group type: Active Comparator
description: Mechanism: A broad-spectrum antiseptic to clean and prepare the skin prior to surgery.
Supplier: BD
arm group label: C - DRAPE
arm group type: Other
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 group label: D - SPONGE
arm group type: Active Comparator
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 group label: E - SKIN PREP and DRAPE
arm group type: Other
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 group label: F - SKIN PREP and SPONGE
arm group type: Active Comparator
description: See descriptions in single arms (B & D)
arm group label: G - DRAPE and SPONGE
arm group type: Other
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 group label: H - SKIN PREP and DRAPE and SPONGE
arm group type: Other
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: 2% alcoholic chlorhexidine skin prep (SKIN PREP)
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).
arm group label: B - SKIN PREP
arm group label: E - SKIN PREP and DRAPE
arm group label: F - SKIN PREP and SPONGE
arm group label: H - SKIN PREP and DRAPE and SPONGE
other name: Chloraprep
intervention type: Device
intervention name: Iodophor Antimicrobial Incise Drapes (DRAPE)
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.
arm group label: C - DRAPE
arm group label: E - SKIN PREP and DRAPE
arm group label: G - DRAPE and SPONGE
arm group label: H - SKIN PREP and DRAPE and SPONGE
other name: Ioban Incise Drape
intervention type: Device
intervention name: Gentamicin-impregnated implants/ sponges (SPONGE)
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.
arm group label: D - SPONGE
arm group label: F - SKIN PREP and SPONGE
arm group label: G - DRAPE and SPONGE
arm group label: H - SKIN PREP and DRAPE and SPONGE
other name: Collatamp G
intervention type: Other
intervention name: NONE (Control)
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 group label: A - NONE (Control)
criteria: 
gender: All
minimum age: 16 Years
maximum age: N/A
healthy volunteers: No
last name: Kayley King
phone: 00 44 121 415 8840
email: k.king.2@bham.ac.uk
last name: ROSSINI 2 Mailbox
email: rossini2@trials.bham.ac.uk
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Surgical Wound Infection
mesh term: Wound Infection
mesh term: Surgical Wound
mesh term: Chlorhexidine
mesh term: Gentamicins
mesh term: Anti-Infective Agents
mesh term: Anti-Bacterial Agents
sharing ipd: No
ipd description: No IPD will be shared with other researchers.
provided document: 