Evaluating the Efficacy and Safety of Intra-wound Vancomycin Powder in High Risk Patients
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|ClinicalTrials.gov Identifier: NCT03839914|
Recruitment Status : Not yet recruiting
First Posted : February 15, 2019
Last Update Posted : October 30, 2019
|First Submitted Date ICMJE||February 9, 2019|
|First Posted Date ICMJE||February 15, 2019|
|Last Update Posted Date||October 30, 2019|
|Estimated Study Start Date ICMJE||April 1, 2020|
|Estimated Primary Completion Date||March 31, 2022 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
|Original Primary Outcome Measures ICMJE
||Surgical site infection rate [ Time Frame: one year ]
To determine whether the difference in surgical site infection rate between the intervention (vancomycin use) and control groups. Our criteria for a surgical site infection is as defined by the Centers for Disease Control and Prevention. The definition includes an infection occurring within 1 year postoperatively with at least one of the following: a) Purulent drainage; b) Organisms isolated from an aseptically obtained culture of fluid or tissue c) At least one sign of symptom of infection: pain or tenderness, localized swelling, redness, or heat or fever d) Diagnosis of surgical site infection by the surgeon
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||Evaluating the Efficacy and Safety of Intra-wound Vancomycin Powder in High Risk Patients|
|Official Title ICMJE||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|
|Brief Summary||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.|
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
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.
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:
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.
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Not Applicable|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Single-blinded open-label randomized controlled trialMasking: Double (Investigator, Outcomes Assessor)
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.Primary Purpose: Treatment
|Intervention ICMJE||Drug: Vancomycin powder
For the intervention group, the use of 1g vancomycin powder to be placed in the deep wound and subcutaneous layer prior to closure.
|Study Arms ICMJE||
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Not yet recruiting|
|Estimated Enrollment ICMJE
|Original Estimated Enrollment ICMJE
|Estimated Study Completion Date ICMJE||September 30, 2022|
|Estimated Primary Completion Date||March 31, 2022 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages ICMJE||18 Years and older (Adult, Older Adult)|
|Accepts Healthy Volunteers ICMJE||No|
|Listed Location Countries ICMJE||Hong Kong|
|Removed Location Countries|
|NCT Number ICMJE||NCT03839914|
|Other Study ID Numbers ICMJE||Study protocol 1.4|
|Has Data Monitoring Committee||Yes|
|U.S. FDA-regulated Product||
|IPD Sharing Statement ICMJE||
|Responsible Party||Dr. Jason Pui Yin Cheung, The University of Hong Kong|
|Study Sponsor ICMJE||The University of Hong Kong|
|Collaborators ICMJE||Not Provided|
|Investigators ICMJE||Not Provided|
|PRS Account||The University of Hong Kong|
|Verification Date||October 2019|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP