<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/NCT03839914</url>
  </required_header>
  <id_info>
    <org_study_id>Study protocol 1.4</org_study_id>
    <nct_id>NCT03839914</nct_id>
  </id_info>
  <brief_title>Evaluating the Efficacy and Safety of Intra-wound Vancomycin Powder in High Risk Patients</brief_title>
  <official_title>Randomized, Controlled, Single-blinded Trial to Evaluate the Efficacy and Safety of Intra-wound Administration of Vancomycin Powder as Add-on Prophylactic Intraoperative Antibiotic in Patients at High Risk for Surgical Site Infections After Receiving Open Posterior Spinal Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The University of Hong Kong</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The University of Hong Kong</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>
      Surgical site infections (SSI) are not uncommon, especially in specific high-risk groups&#xD;
      including spinal deformity and tumor (i.e. metastatic spine surgery) surgery. Well-recognized&#xD;
      measures have been adopted to reduce surgical site infection, and the use of topical&#xD;
      vancomycin powder has gained popularity in recent years. Given the lack of high-quality&#xD;
      evidence for the use of topical vancomycin to reduce surgical site infections in open&#xD;
      posterior spine surgery, which is currently the most common approach to spine surgery, it is&#xD;
      crucial to study the use of vancomycin powder in reducing surgical site infections. This&#xD;
      study is a prospective, single-blinded open label randomized controlled trial, with one arm&#xD;
      of patients having local administration of 1g vancomycin powder which will be placed in the&#xD;
      deep wound and subcutaneous layer prior to closure of surgical site by the orthopaedic&#xD;
      surgeon, whereas the control arm will be without such application of vancomycin. Both arms of&#xD;
      patients will still be undergoing the same operation procedures, as well as postoperative&#xD;
      local wound drainage and wound care. This study will provide insights on the reduction rate&#xD;
      in superficial and/or deep surgical site infection, and also assess the cost-effectiveness of&#xD;
      using topical vancomycin in reducing surgical site infection between different disease&#xD;
      groups, as well as any postoperative serum vancomycin toxicity and renal impairment. These&#xD;
      proposed findings will provide valuable information for clinicians and institutions on future&#xD;
      measures for surgical site infection of open posterior spine surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Objectives:&#xD;
&#xD;
      Primary Objectives:&#xD;
&#xD;
      To evaluate the efficacy of intra-wound administration of vancomycin powder as add-on&#xD;
      prophylactic intraoperative antibiotic in patients at high risk for surgical site infections&#xD;
      after receiving open posterior spinal surgery&#xD;
&#xD;
      Secondary Objectives:&#xD;
&#xD;
        -  To evaluate the safety of intra-wound administration of vancomycin powder as an add-on&#xD;
           prophylactic intraoperative antibiotic&#xD;
&#xD;
        -  To evaluate the cost-effectiveness of intra-wound administration of vancomycin powder as&#xD;
           an add-on prophylactic intraoperative antibiotic compared to standard prophylactic&#xD;
           intraoperative care&#xD;
&#xD;
      Hypothesis to be tested:&#xD;
&#xD;
      The intra-wound vancomycin powder as add-on prophylactic intraoperative antibiotic can&#xD;
      significantly reduce the rate of surgical site infection.&#xD;
&#xD;
      Design and subjects:&#xD;
&#xD;
      The study is a prospective, parallel group, single-blinded randomized controlled trial.&#xD;
&#xD;
      All eligible patients who have consented to take part in the study will be randomized to&#xD;
      either intervention or control group with a 1:1 allocation ratio. Patients allocated to the&#xD;
      intervention group will receive intra-wound vancomycin powder 1gram as add-on prophylactic&#xD;
      intraoperative antibiotic during the surgery. Patients allocated to the control group will&#xD;
      not receive any add-on prophylactic intraoperative antibiotic. Patients will not know their&#xD;
      treatment allocation until study termination.&#xD;
&#xD;
      Surgical site condition of all the patients will be assessed after the surgery. Investigator&#xD;
      will examine the surgical wound and observe any signs and/or symptoms of SSI during&#xD;
      hospitalization and follow-up visits until 1 year post-operation. For patients received&#xD;
      instrumentation and fusion operation, additional radiographs of the operated sites will be&#xD;
      performed for assessing any implant loosening and non-union at 3, 6 and 12 months&#xD;
      postoperatively. All clinical and radiological outcomes will be evaluated throughout the&#xD;
      study period.&#xD;
&#xD;
      Instruments: Parameters include age, gender, smoking and drinking history, pathology&#xD;
      (deformity, tumor, trauma, degenerative), location and spinal levels of surgery, if&#xD;
      instrumentation is used, operative time, blood loss, need for transfusion, significant&#xD;
      co-morbidities including diabetes mellitus, renal failure, immunocompromised state, and dural&#xD;
      tear events.&#xD;
&#xD;
      Interventions: Patients are randomized into the treatment group where 1g of vancomycin powder&#xD;
      is administered to the deep and superficial spinal wound, and the control group without&#xD;
      vancomycin powder use.&#xD;
&#xD;
      Main outcome measures: Primary outcome is the rate of surgical site infection. Secondary&#xD;
      outcomes include vancomycin toxicity measured by vancomycin levels and renal function for&#xD;
      three consecutive postoperative days, and cost-effectiveness calculation for each disease&#xD;
      group. Additionally for those undergoing fusion surgery, 1-year follow-up assessment for&#xD;
      fusion rates.&#xD;
&#xD;
      Data analysis:&#xD;
&#xD;
      For descriptive statistics, means and standard deviations or medians and interquartile ranges&#xD;
      will be presented for continuous variables, frequencies and percentages will be presented for&#xD;
      categorical/ discrete variables.&#xD;
&#xD;
      Baseline Comparison The baseline characteristics of the intervention and control group will&#xD;
      be evaluated. The Student's t-test or Wilcoxon Rank-Sum test (according to the frequency&#xD;
      distribution of the variables studied) will be used to compare continuous variables, and&#xD;
      Chi-square or Fisher's exact test will be used to compare categorical/discrete variables.&#xD;
&#xD;
      Primary Efficacy Analysis Fisher's exact test will be performed to evaluate the difference of&#xD;
      SSI rates between the intervention and control group. The respective 95% confidence interval&#xD;
      (CI) will be calculated and presented. If it is appropriate, the adjustment for baseline&#xD;
      covariates will be made to the primary efficacy comparison. The analysis will primarily be&#xD;
      carried out according to ITT population and subordinately based on PP population. Both ITT&#xD;
      and PP results will be reported.&#xD;
&#xD;
      Adjusted Analysis for Confounding Factors:&#xD;
&#xD;
      If baseline imbalance is observed, adjustment for confounding factors in the primary analysis&#xD;
      will be investigated by a multiple logistic regression for the potential risk factors with&#xD;
      SSI as follows:&#xD;
&#xD;
        -  Patient-related risk factors include socio-demographics and co-morbidities including,&#xD;
           diabetes mellitus, ischemic heart disease, chronic obstructive pulmonary disease, renal&#xD;
           impairment/failure, immunocompromised state and nutritional deficiency.&#xD;
&#xD;
        -  Procedure-related risk factors include type and site of surgery, intraoperative details&#xD;
           including number of spinal level operated, length of instrumentation, use of fusion, use&#xD;
           of drain, operation duration, presence of dural tear and number of surgeons in operating&#xD;
           room&#xD;
&#xD;
        -  Intra- and post-operative blood loss and blood product transfusion.&#xD;
&#xD;
      Cost-effectiveness analysis The cost-effectiveness analysis will estimate the Incremental&#xD;
      cost-effectiveness ratio(ICER), which is the incremental cost per SSI prevented for the&#xD;
      add-on administration of vancomycin powder compared with standard care over a 1-year&#xD;
      post-operative period.&#xD;
&#xD;
      The total cost for SSI will be calculated by multiplying the quantity of resource use by unit&#xD;
      costs. Future costs will be discounted at a rate of 3% per year.&#xD;
&#xD;
      Non-parametric bootstrapping will be used to determine the 95% CIs for ICERs. A&#xD;
      non-parametric bootstrap replications of 1000 with replacement generating multiple data sets&#xD;
      from the original data will be used. In each dataset, the statistic of interest (mean costs,&#xD;
      SSIs, and ICERs) will be calculated. Multiple sensitivity analysis will be performed to&#xD;
      evaluate the robustness of the findings.&#xD;
&#xD;
      Uncertainty in the estimates of the cost-effectiveness evaluation will be visualized by&#xD;
      plotting the cost-effectiveness plane and acceptability curves. The acceptability curves will&#xD;
      be used to determine the probability that the additional use of vancomycin powder will be&#xD;
      cost-effective compared with standard care, at different values of ceiling ratio or&#xD;
      acceptable willingness-to-pay threshold.&#xD;
&#xD;
      The cost-effectiveness analysis will be carried out according to the ITT population.&#xD;
&#xD;
      Safety Analysis The incidence of adverse effects (AEs) will be summarized by system organ&#xD;
      class and severity grading according to the National Cancer Institute (NCI) Common Toxicity&#xD;
      Criteria for Adverse Event (CTCAE) version 5. AEs will be tabulated by severity grading and&#xD;
      relationship with study intervention.&#xD;
&#xD;
      The AESIs will be summarized in similar manner as all AEs. The safety analysis will be&#xD;
      carried out according to in the safety population.&#xD;
&#xD;
      Expected results: Intra-wound administration of vancomycin powder reduces surgical site&#xD;
      infections, is not toxic, and the most cost-effective disease groups are deformity correction&#xD;
      and tumor surgery.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 1, 2020</start_date>
  <completion_date type="Anticipated">March 31, 2025</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2024</primary_completion_date>
  <phase>N/A</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>Single-blinded open-label randomized controlled trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Investigator, Outcomes Assessor)</masking>
    <masking_description>This will be a single blinded trial as patients will not know their treatment allocation until the termination of study. Operating surgeons cannot be blinded to allocation. However, all clinical and radiological outcomes will be evaluated by an independent researcher who is blinded to the allocation. This researcher will be blinded to the study treatment throughout the study period.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of superficial incisional SSI</measure>
    <time_frame>one year</time_frame>
    <description>CDC Surgical Site Infection Criteria (Centers for Disease Control, Procedure-associated Module SSI, January 2019)&#xD;
The definition of SSSI is:&#xD;
an infection occurs within 30 days after operation (where day 1= operation day);&#xD;
AND&#xD;
Involves only skin/subcutaneous tissue of the incision;&#xD;
AND&#xD;
3) Patient has at least one of the following: a)purulent drainage from the superficial incision; b)organism(s) identified from an aseptically-obtained specimen from the superficial incision or subcutaneous tissue by a culture/non-culture based microbiologic testing method; c)superficial incision being deliberately opened by a surgeon, attending doctor/other designee and culture/non-culture based testing of the superficial incision or subcutaneous tissue is not performed AND Patient has at least one of the following: localized pain/tenderness, localized swelling, erythema, or heat; d) SSSI diagnosed by a surgeon, attending doctor/other designee.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of deep incisional SSI</measure>
    <time_frame>one year</time_frame>
    <description>Deep Incisional SSI (DSSI)&#xD;
For deep incisional SSI, the definition is an infection occurring within 90 days after the operation (where day 1 = the procedure day); AND&#xD;
Involves deep soft tissues of the incision (e.g. fascial and muscle layers); AND&#xD;
Patient has at least one of the following:&#xD;
purulent drainage from the deep incision;&#xD;
a deep incision spontaneously dehisces, or is deliberately opened or aspirated by the surgeon, attending doctor or other designee;&#xD;
AND&#xD;
Organism(s) identified from the deep soft tissues of the incision by a culture or non-culture based microbiologic testing method which is performed for purposes of clinical diagnosis or treatment;&#xD;
AND&#xD;
Patient has at least one of the following signs and symptoms: fever (&gt;38 °C); localized pain or tenderness;&#xD;
An abscess or other evidence of infection involving the deep incision that is detected on gross anatomical or histopathologic exam, or imaging test.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with adverse event (AE) to vancomycin</measure>
    <time_frame>one year</time_frame>
    <description>An AE is any untoward medical occurrence to a patient which does not necessarily has a causal relationship with the study intervention, and it can also occur outside of the time period. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), new or exacerbated symptoms/diseases temporally associated with the study intervention, whether or not the event is considered causally related to the use of intervention. Medical conditions/diseases present before the study intervention are only considered as AEs if they worsen after intervention. Signs and symptoms that are clearly due to natural process of underlying disease/disease progression should not be reported. SSSI/DSSI is not regarded as an AE in the study. Secondary infection of a SSSI/DSSI or other infection shall be regarded as an AE.&#xD;
The term AE is used to include both serious and non-serious AE.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cost-effectiveness of vancomycin use</measure>
    <time_frame>one year</time_frame>
    <description>Determination of which disease group is most cost-effective in terms of cost per surgical site infection episode reduced. Will identify the highest risk group (i.e. deformity or tumor surgery) and see whether the risk of infection is significantly different between intervention and control groups as compared to perceived less risk groups (i.e. simple decompression surgery, no implants). Cost items include cost of vancomycin drug, hospitalization days, prolonged antibiotic use, repeated operations for debridement</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incremental cost-effectiveness ratio</measure>
    <time_frame>one year</time_frame>
    <description>It is the incremental cost divided by the difference in the number of SSI cases between treatment group and control group over a 1-year post-operative period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum vancomycin level</measure>
    <time_frame>Three days postoperatively</time_frame>
    <description>3 days postoperative serum assessment of vancomycin levels to identify any vancomycin toxicity in serum</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Renal function test</measure>
    <time_frame>Three days postoperatively</time_frame>
    <description>3 days postoperative serum assessment of renal function tests to identify any renal impairment</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">76</enrollment>
  <condition>Spinal Deformity</condition>
  <condition>Trauma</condition>
  <condition>Spinal Tumor</condition>
  <condition>Surgical Site Infection</condition>
  <arm_group>
    <arm_group_label>Intervention - Vancomycin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Intervention: 1g vancomycin powder locally applied to the deep wound and subcutaneous layer prior to closure.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control - No vancomycin application</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>No intervention, control group All other wound closure procedure and wound care and monitoring are the same</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vancomycin powder</intervention_name>
    <description>For the intervention group, the use of 1g vancomycin powder to be placed in the deep wound and subcutaneous layer prior to closure.</description>
    <arm_group_label>Intervention - Vancomycin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Female or male adult with age ≥18 years&#xD;
&#xD;
          2. Undergoing open posterior spinal surgery with instrumentation indicated for spinal&#xD;
             deformity, trauma and tumor&#xD;
&#xD;
          3. Able to understand the nature, scope and possible consequences of participation in the&#xD;
             study&#xD;
&#xD;
          4. Appropriate voluntary written informed consent have been provided by patients&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Has been treated with antibiotics due to primary spinal infection (i.e.&#xD;
             spondylodiscitis) within 1 year prior to surgery&#xD;
&#xD;
          2. Ongoing treatment with antibiotics for other infections&#xD;
&#xD;
          3. Undergoing minimally invasive surgery or anterior-only surgical approaches or&#xD;
             deformity correction surgery for adolescent idiopathic scoliosis (inherent low-risk&#xD;
             for surgical site infections18)&#xD;
&#xD;
          4. Undergoing decompression-only surgery for cervical spine, spinal deformity, trauma and&#xD;
             tumors&#xD;
&#xD;
          5. Has known history of allergy to vancomycin, penicillin and other glycopeptides&#xD;
             (teicoplanin)&#xD;
&#xD;
          6. Has history of vancomycin resistance&#xD;
&#xD;
          7. Pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Jason PY Cheung</last_name>
    <phone>(852) 22554581</phone>
    <email>cheungjp@hku.hk</email>
  </overall_contact>
  <location>
    <facility>
      <name>Queen Mary Hospital</name>
      <address>
        <city>Hong Kong</city>
        <country>Hong Kong</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Prudence Cheung</last_name>
      <email>gnuehcp6@hotmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>Hong Kong</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>February 9, 2019</study_first_submitted>
  <study_first_submitted_qc>February 12, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 15, 2019</study_first_posted>
  <last_update_submitted>May 10, 2023</last_update_submitted>
  <last_update_submitted_qc>May 10, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 11, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The University of Hong Kong</investigator_affiliation>
    <investigator_full_name>Dr. Jason Pui Yin Cheung</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>vancomycin powder</keyword>
  <keyword>surgical site infection</keyword>
  <keyword>open posterior spinal surgery</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Surgical Wound Infection</mesh_term>
    <mesh_term>Spinal Cord Neoplasms</mesh_term>
    <mesh_term>Spinal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vancomycin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03839914
org study id: Study protocol 1.4
nct id: NCT03839914
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Surgical site infections (SSI) are not uncommon, especially in specific high-risk groups
      including spinal deformity and tumor (i.e. metastatic spine surgery) surgery. Well-recognized
      measures have been adopted to reduce surgical site infection, and the use of topical
      vancomycin powder has gained popularity in recent years. Given the lack of high-quality
      evidence for the use of topical vancomycin to reduce surgical site infections in open
      posterior spine surgery, which is currently the most common approach to spine surgery, it is
      crucial to study the use of vancomycin powder in reducing surgical site infections. This
      study is a prospective, single-blinded open label randomized controlled trial, with one arm
      of patients having local administration of 1g vancomycin powder which will be placed in the
      deep wound and subcutaneous layer prior to closure of surgical site by the orthopaedic
      surgeon, whereas the control arm will be without such application of vancomycin. Both arms of
      patients will still be undergoing the same operation procedures, as well as postoperative
      local wound drainage and wound care. This study will provide insights on the reduction rate
      in superficial and/or deep surgical site infection, and also assess the cost-effectiveness of
      using topical vancomycin in reducing surgical site infection between different disease
      groups, as well as any postoperative serum vancomycin toxicity and renal impairment. These
      proposed findings will provide valuable information for clinicians and institutions on future
      measures for surgical site infection of open posterior spine surgery.
Objectives:

      Primary Objectives:

      To evaluate the efficacy of intra-wound administration of vancomycin powder as add-on
      prophylactic intraoperative antibiotic in patients at high risk for surgical site infections
      after receiving open posterior spinal surgery

      Secondary Objectives:

        -  To evaluate the safety of intra-wound administration of vancomycin powder as an add-on
           prophylactic intraoperative antibiotic

        -  To evaluate the cost-effectiveness of intra-wound administration of vancomycin powder as
           an add-on prophylactic intraoperative antibiotic compared to standard prophylactic
           intraoperative care

      Hypothesis to be tested:

      The intra-wound vancomycin powder as add-on prophylactic intraoperative antibiotic can
      significantly reduce the rate of surgical site infection.

      Design and subjects:

      The study is a prospective, parallel group, single-blinded randomized controlled trial.

      All eligible patients who have consented to take part in the study will be randomized to
      either intervention or control group with a 1:1 allocation ratio. Patients allocated to the
      intervention group will receive intra-wound vancomycin powder 1gram as add-on prophylactic
      intraoperative antibiotic during the surgery. Patients allocated to the control group will
      not receive any add-on prophylactic intraoperative antibiotic. Patients will not know their
      treatment allocation until study termination.

      Surgical site condition of all the patients will be assessed after the surgery. Investigator
      will examine the surgical wound and observe any signs and/or symptoms of SSI during
      hospitalization and follow-up visits until 1 year post-operation. For patients received
      instrumentation and fusion operation, additional radiographs of the operated sites will be
      performed for assessing any implant loosening and non-union at 3, 6 and 12 months
      postoperatively. All clinical and radiological outcomes will be evaluated throughout the
      study period.

      Instruments: Parameters include age, gender, smoking and drinking history, pathology
      (deformity, tumor, trauma, degenerative), location and spinal levels of surgery, if
      instrumentation is used, operative time, blood loss, need for transfusion, significant
      co-morbidities including diabetes mellitus, renal failure, immunocompromised state, and dural
      tear events.

      Interventions: Patients are randomized into the treatment group where 1g of vancomycin powder
      is administered to the deep and superficial spinal wound, and the control group without
      vancomycin powder use.

      Main outcome measures: Primary outcome is the rate of surgical site infection. Secondary
      outcomes include vancomycin toxicity measured by vancomycin levels and renal function for
      three consecutive postoperative days, and cost-effectiveness calculation for each disease
      group. Additionally for those undergoing fusion surgery, 1-year follow-up assessment for
      fusion rates.

      Data analysis:

      For descriptive statistics, means and standard deviations or medians and interquartile ranges
      will be presented for continuous variables, frequencies and percentages will be presented for
      categorical/ discrete variables.

      Baseline Comparison The baseline characteristics of the intervention and control group will
      be evaluated. The Student's t-test or Wilcoxon Rank-Sum test (according to the frequency
      distribution of the variables studied) will be used to compare continuous variables, and
      Chi-square or Fisher's exact test will be used to compare categorical/discrete variables.

      Primary Efficacy Analysis Fisher's exact test will be performed to evaluate the difference of
      SSI rates between the intervention and control group. The respective 95% confidence interval
      (CI) will be calculated and presented. If it is appropriate, the adjustment for baseline
      covariates will be made to the primary efficacy comparison. The analysis will primarily be
      carried out according to ITT population and subordinately based on PP population. Both ITT
      and PP results will be reported.

      Adjusted Analysis for Confounding Factors:

      If baseline imbalance is observed, adjustment for confounding factors in the primary analysis
      will be investigated by a multiple logistic regression for the potential risk factors with
      SSI as follows:

        -  Patient-related risk factors include socio-demographics and co-morbidities including,
           diabetes mellitus, ischemic heart disease, chronic obstructive pulmonary disease, renal
           impairment/failure, immunocompromised state and nutritional deficiency.

        -  Procedure-related risk factors include type and site of surgery, intraoperative details
           including number of spinal level operated, length of instrumentation, use of fusion, use
           of drain, operation duration, presence of dural tear and number of surgeons in operating
           room

        -  Intra- and post-operative blood loss and blood product transfusion.

      Cost-effectiveness analysis The cost-effectiveness analysis will estimate the Incremental
      cost-effectiveness ratio(ICER), which is the incremental cost per SSI prevented for the
      add-on administration of vancomycin powder compared with standard care over a 1-year
      post-operative period.

      The total cost for SSI will be calculated by multiplying the quantity of resource use by unit
      costs. Future costs will be discounted at a rate of 3% per year.

      Non-parametric bootstrapping will be used to determine the 95% CIs for ICERs. A
      non-parametric bootstrap replications of 1000 with replacement generating multiple data sets
      from the original data will be used. In each dataset, the statistic of interest (mean costs,
      SSIs, and ICERs) will be calculated. Multiple sensitivity analysis will be performed to
      evaluate the robustness of the findings.

      Uncertainty in the estimates of the cost-effectiveness evaluation will be visualized by
      plotting the cost-effectiveness plane and acceptability curves. The acceptability curves will
      be used to determine the probability that the additional use of vancomycin powder will be
      cost-effective compared with standard care, at different values of ceiling ratio or
      acceptable willingness-to-pay threshold.

      The cost-effectiveness analysis will be carried out according to the ITT population.

      Safety Analysis The incidence of adverse effects (AEs) will be summarized by system organ
      class and severity grading according to the National Cancer Institute (NCI) Common Toxicity
      Criteria for Adverse Event (CTCAE) version 5. AEs will be tabulated by severity grading and
      relationship with study intervention.

      The AESIs will be summarized in similar manner as all AEs. The safety analysis will be
      carried out according to in the safety population.

      Expected results: Intra-wound administration of vancomycin powder reduces surgical site
      infections, is not toxic, and the most cost-effective disease groups are deformity correction
      and tumor surgery.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Single-blinded open-label randomized controlled trial
primary purpose: Treatment
masking: Double (Investigator, Outcomes Assessor)
masking description: This will be a single blinded trial as patients will not know their treatment allocation until the termination of study. Operating surgeons cannot be blinded to allocation. However, all clinical and radiological outcomes will be evaluated by an independent researcher who is blinded to the allocation. This researcher will be blinded to the study treatment throughout the study period.
measure: Incidence of superficial incisional SSI
time frame: one year
description: CDC Surgical Site Infection Criteria (Centers for Disease Control, Procedure-associated Module SSI, January 2019)
The definition of SSSI is:
an infection occurs within 30 days after operation (where day 1= operation day);
AND
Involves only skin/subcutaneous tissue of the incision;
AND
3) Patient has at least one of the following: a)purulent drainage from the superficial incision; b)organism(s) identified from an aseptically-obtained specimen from the superficial incision or subcutaneous tissue by a culture/non-culture based microbiologic testing method; c)superficial incision being deliberately opened by a surgeon, attending doctor/other designee and culture/non-culture based testing of the superficial incision or subcutaneous tissue is not performed AND Patient has at least one of the following: localized pain/tenderness, localized swelling, erythema, or heat; d) SSSI diagnosed by a surgeon, attending doctor/other designee.
measure: Incidence of deep incisional SSI
time frame: one year
description: Deep Incisional SSI (DSSI)
For deep incisional SSI, the definition is an infection occurring within 90 days after the operation (where day 1 = the procedure day); AND
Involves deep soft tissues of the incision (e.g. fascial and muscle layers); AND
Patient has at least one of the following:
purulent drainage from the deep incision;
a deep incision spontaneously dehisces, or is deliberately opened or aspirated by the surgeon, attending doctor or other designee;
AND
Organism(s) identified from the deep soft tissues of the incision by a culture or non-culture based microbiologic testing method which is performed for purposes of clinical diagnosis or treatment;
AND
Patient has at least one of the following signs and symptoms: fever (>38 °C); localized pain or tenderness;
An abscess or other evidence of infection involving the deep incision that is detected on gross anatomical or histopathologic exam, or imaging test.
measure: Number of participants with adverse event (AE) to vancomycin
time frame: one year
description: An AE is any untoward medical occurrence to a patient which does not necessarily has a causal relationship with the study intervention, and it can also occur outside of the time period. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), new or exacerbated symptoms/diseases temporally associated with the study intervention, whether or not the event is considered causally related to the use of intervention. Medical conditions/diseases present before the study intervention are only considered as AEs if they worsen after intervention. Signs and symptoms that are clearly due to natural process of underlying disease/disease progression should not be reported. SSSI/DSSI is not regarded as an AE in the study. Secondary infection of a SSSI/DSSI or other infection shall be regarded as an AE.
The term AE is used to include both serious and non-serious AE.
measure: Cost-effectiveness of vancomycin use
time frame: one year
description: Determination of which disease group is most cost-effective in terms of cost per surgical site infection episode reduced. Will identify the highest risk group (i.e. deformity or tumor surgery) and see whether the risk of infection is significantly different between intervention and control groups as compared to perceived less risk groups (i.e. simple decompression surgery, no implants). Cost items include cost of vancomycin drug, hospitalization days, prolonged antibiotic use, repeated operations for debridement
measure: Incremental cost-effectiveness ratio
time frame: one year
description: It is the incremental cost divided by the difference in the number of SSI cases between treatment group and control group over a 1-year post-operative period.
measure: Serum vancomycin level
time frame: Three days postoperatively
description: 3 days postoperative serum assessment of vancomycin levels to identify any vancomycin toxicity in serum
measure: Renal function test
time frame: Three days postoperatively
description: 3 days postoperative serum assessment of renal function tests to identify any renal impairment
arm group label: Intervention - Vancomycin
arm group type: Active Comparator
description: Intervention: 1g vancomycin powder locally applied to the deep wound and subcutaneous layer prior to closure.
arm group label: Control - No vancomycin application
arm group type: No Intervention
description: No intervention, control group All other wound closure procedure and wound care and monitoring are the same
intervention type: Drug
intervention name: Vancomycin powder
description: For the intervention group, the use of 1g vancomycin powder to be placed in the deep wound and subcutaneous layer prior to closure.
arm group label: Intervention - Vancomycin
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jason PY Cheung
phone: (852) 22554581
email: cheungjp@hku.hk
facility: 
status: Recruiting
contact: 
country: Hong Kong
responsible party type: Principal Investigator
investigator affiliation: The University of Hong Kong
investigator full name: Dr. Jason Pui Yin Cheung
investigator title: Associate Professor
mesh term: Infections
mesh term: Surgical Wound Infection
mesh term: Spinal Cord Neoplasms
mesh term: Spinal Neoplasms
mesh term: Vancomycin
sharing ipd: No