Arthropathy of Knee Joint
Conditions
Keywords
Revision knee joint
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 preventing infection than the current standard dose which is given intravenously (IV) through a wrist vein.
Detailed description
Patients were assigned to one of two groups by chance (like a coin toss): * GROUP 1 - Received 500mg of vancomycin into the tibia (shin) bone of the leg being operated on. * GROUP 2 - Received 1g of vancomycin, which is the amount normally given to patients. For both groups, the revision knee replacement will then be carried out as normal. OTHER ANTIBIOTICS All patients received cefazolin IV (an antibiotic used to prevent infection) prior to the beginning of surgery to ensure effective preventive antibiotics. The patient will also received 3 postoperative doses of cefazolin over a 24-hour period (4 doses in total). This is standard of care for all total knee replacement surgeries. TISSUE SAMPLES * Ten (10) tissue samples were taken during the surgery, consisting of both bone and fat beneath the skin. Each sample were very small, around the size of a pinhead. * In addition, a drain sample was taken from the knee joint drain fluid to measure vancomycin concentration the morning following surgery. * These samples were frozen and sent to a lab for analysis.
Interventions
DRUGVancomycin
Sponsors
Vidacare Corporation
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Revision total knee arthroplasty * Informed consent given
Exclusion criteria
* Current treatment with IV Vancomycin within the preceding 7 days * Previous hypersensitivity to vancomycin * Significant cardiac or respiratory abnormality * Contraindications to using the intraosseous vascular access system (EZ-IO) * Sepsis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Concentration of Vancomycin in Subcutaneous Fat | Baseline to 24 hours | During the procedure, subcutaneous fat samples (approximately 0.5 cm\^3) were taken at regular intervals until skin closure. Vancomycin concentrations were determined by liquid chromatography coupled with tandem mass spectrometry. Times are given as minutes post surgical incision. |
| Mean Concentration of Vancomycin in Bone Samples | baseline to 24 hours | During the procedure, bone samples (approximately 0.5 cm\^3) were taken at regular intervals were taken at regular intervals until skin closure. All bone samples were taken from the femur, distant from the tibial intraosseous injection site. Vancomycin concentrations were determined by liquid chromatography coupled with tandem mass spectrometry. Times are given as minutes post surgical incision. |
Countries
United States
Participant flow
Recruitment details
Subjects were enrolled between January 2014 and April 2015 at Mayo Clinic in Arizona.
Participants by arm
| Arm | Count |
|---|---|
| Vancomycin 500mg Intraosseous Vancomycin 500mg is given via intraosseous regional administration (IORA) into a proximal tibial cannula, after tourniquet inflation and immediately prior to skin incision. | 10 |
| Vancomycin 1g IV Vancomycin 1g is administered via forearm vein, given over a one-hour infusion, timed to finish approximately 30 minutes prior to tourniquet inflation. | 10 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 1 | 1 |
Baseline characteristics
| Characteristic | Vancomycin 500mg Intraosseous | Vancomycin 1g IV | Total |
|---|---|---|---|
| Age, Continuous | 69.3 years | 67.4 years | 68.4 years |
| Region of Enrollment United States | 10 participants | 10 participants | 20 participants |
| Sex: Female, Male Female | 7 Participants | 5 Participants | 12 Participants |
| Sex: Female, Male Male | 3 Participants | 5 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 10 | 3 / 10 |
| serious Total, serious adverse events | 4 / 10 | 0 / 10 |
Outcome results
Primary
Mean Concentration of Vancomycin in Bone Samples
During the procedure, bone samples (approximately 0.5 cm\^3) were taken at regular intervals were taken at regular intervals until skin closure. All bone samples were taken from the femur, distant from the tibial intraosseous injection site. Vancomycin concentrations were determined by liquid chromatography coupled with tandem mass spectrometry. Times are given as minutes post surgical incision.
Time frame: baseline to 24 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vancomycin 500mg Intraosseous | Mean Concentration of Vancomycin in Bone Samples | At approximately 30 minutes | 90.7 µg/g | Standard Deviation 77 |
| Vancomycin 500mg Intraosseous | Mean Concentration of Vancomycin in Bone Samples | At approximately 50 minutes | 193 µg/g | Standard Deviation 191 |
| Vancomycin 500mg Intraosseous | Mean Concentration of Vancomycin in Bone Samples | At approximately 115 minutes | 59.8 µg/g | Standard Deviation 63 |
| Vancomycin 500mg Intraosseous | Mean Concentration of Vancomycin in Bone Samples | At approximately 145 minutes | 62.9 µg/g | Standard Deviation 62 |
| Vancomycin 1g IV | Mean Concentration of Vancomycin in Bone Samples | At approximately 145 minutes | 7.1 µg/g | Standard Deviation 4.4 |
| Vancomycin 1g IV | Mean Concentration of Vancomycin in Bone Samples | At approximately 30 minutes | 7.9 µg/g | Standard Deviation 5.7 |
| Vancomycin 1g IV | Mean Concentration of Vancomycin in Bone Samples | At approximately 115 minutes | 5.0 µg/g | Standard Deviation 2.3 |
| Vancomycin 1g IV | Mean Concentration of Vancomycin in Bone Samples | At approximately 50 minutes | 8.6 µg/g | Standard Deviation 5.9 |
Primary
Mean Concentration of Vancomycin in Subcutaneous Fat
During the procedure, subcutaneous fat samples (approximately 0.5 cm\^3) were taken at regular intervals until skin closure. Vancomycin concentrations were determined by liquid chromatography coupled with tandem mass spectrometry. Times are given as minutes post surgical incision.
Time frame: Baseline to 24 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vancomycin 500mg Intraosseous | Mean Concentration of Vancomycin in Subcutaneous Fat | At approximately 3 minutes | 94.1 µg/g | Standard Deviation 69 |
| Vancomycin 500mg Intraosseous | Mean Concentration of Vancomycin in Subcutaneous Fat | At approximately 30 minutes | 88.3 µg/g | Standard Deviation 131 |
| Vancomycin 500mg Intraosseous | Mean Concentration of Vancomycin in Subcutaneous Fat | At approximately 50 minutes | 69.4 µg/g | Standard Deviation 50 |
| Vancomycin 500mg Intraosseous | Mean Concentration of Vancomycin in Subcutaneous Fat | At approximately 115 minutes | 173 µg/g | Standard Deviation 445 |
| Vancomycin 500mg Intraosseous | Mean Concentration of Vancomycin in Subcutaneous Fat | At approximately 150 minutes | 249 µg/g | Standard Deviation 639 |
| Vancomycin 500mg Intraosseous | Mean Concentration of Vancomycin in Subcutaneous Fat | At approximately 180 minutes | 18.2 µg/g | Standard Deviation 11.6 |
| Vancomycin 1g IV | Mean Concentration of Vancomycin in Subcutaneous Fat | At approximately 150 minutes | 4.0 µg/g | Standard Deviation 2.2 |
| Vancomycin 1g IV | Mean Concentration of Vancomycin in Subcutaneous Fat | At approximately 3 minutes | 3.2 µg/g | Standard Deviation 1.8 |
| Vancomycin 1g IV | Mean Concentration of Vancomycin in Subcutaneous Fat | At approximately 115 minutes | 4.7 µg/g | Standard Deviation 2.6 |
| Vancomycin 1g IV | Mean Concentration of Vancomycin in Subcutaneous Fat | At approximately 30 minutes | 5.0 µg/g | Standard Deviation 2.9 |
| Vancomycin 1g IV | Mean Concentration of Vancomycin in Subcutaneous Fat | At approximately 180 minutes | 3.6 µg/g | Standard Deviation 2.5 |
| Vancomycin 1g IV | Mean Concentration of Vancomycin in Subcutaneous Fat | At approximately 50 minutes | 4.2 µg/g | Standard Deviation 2.5 |
Comparison: Comparison at approximately 3 minutes, adjusted by BMI, age, and length of surgical procedure.p-value: <0.0001ANOVA
Comparison: Comparison at approximately 30 minutes, adjusted by BMI, age, and length of surgical procedure.p-value: <0.0001ANOVA
Comparison: Comparison at approximately 50 minutes, adjusted by BMI, age, and length of surgical procedure.p-value: <0.0001ANOVA
Comparison: Comparison at approximately 115 minutes, adjusted by BMI, age, and length of surgical procedure.p-value: <0.0001ANOVA
Comparison: Comparison at approximately 150 minutes, adjusted by BMI, age, and length of surgical procedure.p-value: <0.0001ANOVA
Comparison: Comparison at approximately 180 minutes, adjusted by BMI, age, and length of surgical procedure.p-value: <0.0001ANOVA