Regional Prophylactic Vancomycin With Restricted Tourniquet Time in Primary Total Knee Replacement
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
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:
|
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:
|
Outcome Measures
Primary Outcome Measures
- Vancomycin Concentration in Fat [Approximately 60 minutes post surgical incision]
Mean vancomycin concentration in fat measured in ug/g at surgical closure
- 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
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.- 17-007853
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
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 |
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
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 |
Spangehl.Mark@mayo.edu |
- 17-007853