Regional Prophylactic Vancomycin With Restricted Tourniquet Time in Primary Total Knee Replacement

Sponsor
Mayo Clinic (Other)
Overall Status
Completed
CT.gov ID
NCT03506347
Collaborator
(none)
24
1
2
3.8
6.4

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether or not giving a lower dose of antibiotics (Vancomycin) in the area where it is needed (the knee joint) is more effective at obtaining adequate tissue levels of the antibiotic than the current standard dose which is given intravenously (IV) through a wrist vein. The use of intraosseous regional administration (IORA) of vancomycin requires the use of a tourniquet for the duration of the procedure. Many surgeons prefer to perform the surgery with tourniquet use minimised or without a tourniquet at all. The aim of this study is to evaluate whether IORA vancomycin can achieve effective tissue concentrations with tourniquet use minimised.

Condition or Disease Intervention/Treatment Phase
Phase 2/Phase 3

Detailed Description

Patients are assigned to one of two groups by chance (like a coin toss):

GROUP A - Will receive 15mg/kg based on actual body weight (maximum of 2g) of vancomycin via the systemic route at a rate of 15mg/kg as per hospital guidelines. Systemic IV vancomycin is given via a forearm vein, given over an infusion timed to finish immediately prior to surgery.

GROUP B - Will have the limb exsanguinated and an above knee tourniquet inflated to 300 mmHg. Immediately following tourniquet inflation, Group B will receive 500mg of vancomycin, via an EZ-IO intraosseous cannula. The vancomycin would be administered in 150ml of saline solution. The intraosseous cannula would be placed into the epiphysis of the proximal tibia. The tourniquet will be left inflated for 10 minutes following completion of the IORA injection then deflated.

Both Groups will receive weight-based dose of systemic cefazolin ( or alternative antibiotic if allergic to cefazolin 15 minutes prior to inflation of tourniquet. This ensures all patients in the study receive effective antibiotic prophylaxis regardless of randomization. Both groups of patients would then undergo routine prep and draping For both groups, Total knee replacement would then be carried out as normal and the tourniquet will be inflated for cementation of the implants.

TISSUE SAMPLES Ten (10) tissue samples will be taken from each patient, 6 'fat' samples and 4 'bone' samples. Each sample is very small, around the size of a pinhead. Bone samples will be taken from the femur only to ensure no direct contamination from the site of injection (tibia) In addition, drain samples will be taken from the intra-articular drain site to measure vancomycin concentration the morning following surgery.

Three blood samples will be taken in both groups, intraoperatively, in recovery, and the following morning.

These samples are frozen and sent to a lab for analysis.

Study Design

Study Type:
Interventional
Actual Enrollment :
24 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Prevention
Official Title:
Regional Prophylactic Vancomycin With Restricted Tourniquet Time in Primary Total Knee Replacement
Actual Study Start Date :
Sep 24, 2018
Actual Primary Completion Date :
Jan 17, 2019
Actual Study Completion Date :
Jan 17, 2019

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Vancomycin 15mg/kg IV

Will receive 15mg/kg based on actual body weight (maximum of 2g) of vancomycin via the systemic route at a rate of 15mg/kg as per hospital guidelines. Systemic IV vancomycin is given via a forearm vein, given over an infusion timed to finish immediately prior to surgery.

Drug: Vancomycin
Antibiotic
Other Names:
  • Vancocin
  • Experimental: Vancomycin 500mg Intraosseous

    Will have the limb exsanguinated and an above knee tourniquet inflated to 300 mmHg. Immediately following tourniquet inflation, Group B will receive 500mg of vancomycin, via an EZ-IO intraosseous cannula. The vancomycin would be administered in 150ml of saline solution. The intraosseous cannula would be placed into the epiphysis of the proximal tibia. The tourniquet will be left inflated for 10 minutes following completion of the IORA injection then deflated.

    Drug: Vancomycin
    Antibiotic
    Other Names:
  • Vancocin
  • Outcome Measures

    Primary Outcome Measures

    1. Vancomycin Concentration in Fat [Approximately 60 minutes post surgical incision]

      Mean vancomycin concentration in fat measured in ug/g at surgical closure

    2. Vancomycin Concentration in Bone [Approximately 60 minutes post surgical incision]

      Mean vancomycin concentration in bone measured in ug/g at surgical closure

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    Inclusion Criteria

    Primary Total Knee Arthroplasty for osteoarthritis Informed consent given

    Exclusion Criteria

    Current or treatment with IV Vancomycin within preceding 7 days Previous hypersensitivity to vancomycin Significant cardiac or respiratory abnormality Patient has contraindications to IO vascular access using the EZ-IO

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Mayo Clinic in Arizona Scottsdale Arizona United States 85259

    Sponsors and Collaborators

    • Mayo Clinic

    Investigators

    • Principal Investigator: Mark J Spangehl, Mayo Clinic

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Mark J. Spangehl, M.D., Principal Investigator, Mayo Clinic
    ClinicalTrials.gov Identifier:
    NCT03506347
    Other Study ID Numbers:
    • 17-007853
    First Posted:
    Apr 24, 2018
    Last Update Posted:
    Jan 27, 2020
    Last Verified:
    Jan 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Vancomycin 15mg/kg IV Vancomycin 500mg Intraosseous
    Arm/Group Description Will receive 15mg/kg based on actual body weight (maximum of 2g) of vancomycin via the systemic route at a rate of 15mg/kg as per hospital guidelines. Systemic IV vancomycin is given via a forearm vein, given over an infusion timed to finish immediately prior to surgery. Vancomycin: Antibiotic Will have the limb exsanguinated and an above knee tourniquet inflated to 300 mmHg. Immediately following tourniquet inflation, Group B will receive 500mg of vancomycin, via an EZ-IO intraosseous cannula. The vancomycin would be administered in 150ml of saline solution. The intraosseous cannula would be placed into the epiphysis of the proximal tibia. The tourniquet will be left inflated for 10 minutes following completion of the intraosseous regional administration (IORA) injection then deflated. Vancomycin: Antibiotic
    Period Title: Overall Study
    STARTED 12 12
    COMPLETED 12 12
    NOT COMPLETED 0 0

    Baseline Characteristics

    Arm/Group Title Vancomycin 15mg/kg IV Vancomycin 500mg Intraosseous Total
    Arm/Group Description Will receive 15mg/kg based on actual body weight (maximum of 2g) of vancomycin via the systemic route at a rate of 15mg/kg as per hospital guidelines. Systemic IV vancomycin is given via a forearm vein, given over an infusion timed to finish immediately prior to surgery. Vancomycin: Antibiotic Will have the limb exsanguinated and an above knee tourniquet inflated to 300 mmHg. Immediately following tourniquet inflation, Group B will receive 500mg of vancomycin, via an EZ-IO intraosseous cannula. The vancomycin would be administered in 150ml of saline solution. The intraosseous cannula would be placed into the epiphysis of the proximal tibia. The tourniquet will be left inflated for 10 minutes following completion of the IORA injection then deflated. Vancomycin: Antibiotic Total of all reporting groups
    Overall Participants 12 12 24
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    68
    (8.29)
    69.1
    (8.15)
    68
    (8.07)
    Sex: Female, Male (Count of Participants)
    Female
    7
    58.3%
    5
    41.7%
    12
    50%
    Male
    5
    41.7%
    7
    58.3%
    12
    50%
    Race and Ethnicity Not Collected (Count of Participants)
    Count of Participants [Participants]
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    12
    100%
    12
    100%
    24
    100%

    Outcome Measures

    1. Primary Outcome
    Title Vancomycin Concentration in Fat
    Description Mean vancomycin concentration in fat measured in ug/g at surgical closure
    Time Frame Approximately 60 minutes post surgical incision

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Vancomycin 15mg/kg IV Vancomycin 500mg Intraosseous
    Arm/Group Description Will receive 15mg/kg based on actual body weight (maximum of 2g) of vancomycin via the systemic route at a rate of 15mg/kg as per hospital guidelines. Systemic IV vancomycin is given via a forearm vein, given over an infusion timed to finish immediately prior to surgery. Vancomycin: Antibiotic Will have the limb exsanguinated and an above knee tourniquet inflated to 300 mmHg. Immediately following tourniquet inflation, Group B will receive 500mg of vancomycin, via an EZ-IO intraosseous cannula. The vancomycin would be administered in 150ml of saline solution. The intraosseous cannula would be placed into the epiphysis of the proximal tibia. The tourniquet will be left inflated for 10 minutes following completion of the IORA injection then deflated. Vancomycin: Antibiotic
    Measure Participants 12 12
    Measure fat 72 72
    Mean (Standard Deviation) [ug/g]
    6.0
    (0.85)
    40.5
    (8.08)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Vancomycin 15mg/kg IV, Vancomycin 500mg Intraosseous
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.001
    Comments
    Method ANOVA
    Comments
    2. Primary Outcome
    Title Vancomycin Concentration in Bone
    Description Mean vancomycin concentration in bone measured in ug/g at surgical closure
    Time Frame Approximately 60 minutes post surgical incision

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Vancomycin 15mg/kg IV Vancomycin 500mg Intraosseous
    Arm/Group Description Will receive 15mg/kg based on actual body weight (maximum of 2g) of vancomycin via the systemic route at a rate of 15mg/kg as per hospital guidelines. Systemic IV vancomycin is given via a forearm vein, given over an infusion timed to finish immediately prior to surgery. Vancomycin: Antibiotic Will have the limb exsanguinated and an above knee tourniquet inflated to 300 mmHg. Immediately following tourniquet inflation, Group B will receive 500mg of vancomycin, via an EZ-IO intraosseous cannula. The vancomycin would be administered in 150ml of saline solution. The intraosseous cannula would be placed into the epiphysis of the proximal tibia. The tourniquet will be left inflated for 10 minutes following completion of the IORA injection then deflated. Vancomycin: Antibiotic
    Measure Participants 12 12
    Measure bone 48 48
    Mean (Standard Deviation) [ug/g]
    8.3
    (0.77)
    26.9
    (1.31)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Vancomycin 15mg/kg IV, Vancomycin 500mg Intraosseous
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.009
    Comments
    Method ANOVA
    Comments

    Adverse Events

    Time Frame Adverse events were collected from approximately 90 minutes prior to surgery to the morning after surgery for each subject, over the duration of approximately four months.
    Adverse Event Reporting Description
    Arm/Group Title Vancomycin 15mg/kg IV Vancomycin 500mg Intraosseous
    Arm/Group Description Will receive 15mg/kg based on actual body weight (maximum of 2g) of vancomycin via the systemic route at a rate of 15mg/kg as per hospital guidelines. Systemic IV vancomycin is given via a forearm vein, given over an infusion timed to finish immediately prior to surgery. Vancomycin: Antibiotic Will have the limb exsanguinated and an above knee tourniquet inflated to 300 mmHg. Immediately following tourniquet inflation, Group B will receive 500mg of vancomycin, via an EZ-IO intraosseous cannula. The vancomycin would be administered in 150ml of saline solution. The intraosseous cannula would be placed into the epiphysis of the proximal tibia. The tourniquet will be left inflated for 10 minutes following completion of the IORA injection then deflated. Vancomycin: Antibiotic
    All Cause Mortality
    Vancomycin 15mg/kg IV Vancomycin 500mg Intraosseous
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/12 (0%) 0/12 (0%)
    Serious Adverse Events
    Vancomycin 15mg/kg IV Vancomycin 500mg Intraosseous
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/12 (0%) 0/12 (0%)
    Other (Not Including Serious) Adverse Events
    Vancomycin 15mg/kg IV Vancomycin 500mg Intraosseous
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/12 (0%) 0/12 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Mark Spangehl
    Organization Mayo Clinic
    Phone 480-342-2948
    Email Spangehl.Mark@mayo.edu
    Responsible Party:
    Mark J. Spangehl, M.D., Principal Investigator, Mayo Clinic
    ClinicalTrials.gov Identifier:
    NCT03506347
    Other Study ID Numbers:
    • 17-007853
    First Posted:
    Apr 24, 2018
    Last Update Posted:
    Jan 27, 2020
    Last Verified:
    Jan 1, 2020