Joint Diseases, Prosthetic Joint Infection, Vancomycin
Conditions
Keywords
total hip arthroplasty, vancomycin, intraosseous vancomycin
Brief summary
The objective of this study is to evaluate a novel vancomycin intraosseous administration protocol vs a standard IV vancomycin administration protocol for primary total hip arthroplasty patients.
Detailed description
Patients are randomized to one of two groups. GROUP A - Will receive IV antibiotics (cefepime & vancomycin) are started in pre-op approximately 1 hour prior to incision vancomycin dose weight-based at approximately 15mg/kg, generally 1000-1750mg in 500 milliliters (mL) normal saline (NS). GROUP B - Will have IV cefepime started in pre-op within 1 hour of incision. Intraosseous (IO) administration of vancomycin (500mg in 250 milliliters NS) will be administered in the OR after sterile prep and draping has occurred. Injection will take place into the greater trochanter (within a pre-specified region). Both Groups will be monitored during surgery and immediately post-operatively for adverse injection reactions (i.e. Red Man Syndrome). Both groups will otherwise follow identical post-operative protocols (including post-operative antibiotic administration). TISSUE SAMPLES Five (5) tissue samples will be taken from each patient, 2 soft tissue samples and 3 bone samples will be taken throughout the course of the procedure. One blood sample will be taken in both groups intraoperatively at the time of initiation of closure. These samples will immediately be sent to a lab for analysis.
Interventions
DRUGExperimental Intraosseous vancomycin 500mg in 250 mL NS
500mg of Vancomycin in 250 mL of normal saline will be injected into a pre-specified region of the greater trochanter during primary total hip arthroplasty.
DRUGStandard IV administration of vancomycin
IV antibiotics (cefepime & vancomycin) are started in pre-op approximately 1 hour prior to incision (vancomycin dose weight-based at approximately 15mg/kg, generally 1000-1750mg in 500 mL NS).
Sponsors
The Methodist Hospital Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient is undergoing a primary total hip arthroplasty * Patient gives informed consent to participate in the study. * Age Range \>18
Exclusion criteria
* Previous surgery on the hip (including hip scopes) * BMI above 35 * Contraindication to receiving vancomycin or cefepime (allergy, medical issue, etc) * Inability to locate the greater trochanter or administer the IO infusion * Refusal to participate * Diabetes * Immunocompromised or immunosuppressed patients (HIV, Hep C, End stage renal disease, dialysis, transplant, chemo/radiation treatment in last 6 months, medications).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Systemic Vancomycin Level - Start of Case | approximately 10 minutes before incision | vancomycin blood level before the time of incision - typically taken approximately 10 minutes before incision. |
| Systemic Vancomycin Level - End of Case | end of surgical case | — |
| Vancomycin Concentration of Pulvinar Soft Tissue | intraoperative | vancomycin concentration (ug/mL) of pulvinar soft tissue. Vancomycin tissue concentration measured by high performance liquid chromotagraphy. |
| Vancomycin Concentration of Intramedullary Bone | intraoperative | Vancomycin Concentration of Intramedullary Bone in units ug/mL. Vancomycin tissue concentration measured by high performance liquid chromotagraphy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 90-Day Complications | From the administration of antibiotics perioperatively to 90 days post op. | Complications 90 days post surgery eg. infection |
| Soft Tissue Vancomycin Level - Start of Case | at start of case within 15 minutes after incision | at start , soft tissue. Vancomycin tissue concentration (ug/mL) measured by high performance liquid chromatography. |
| Soft Tissue Vancomycin Level - End of Case | right before wound closure is initiated at the end of the case | soft tissue taken at end of case, right before wound closure is initiated. Vancomycin tissue concentration (ug/mL) measured by high performance liquid chromatography. |
| Femur Vancomycin Concentration Level | intraoperative | Intraoperative femur bone sample measured for vancomycin concentration (ug/mL). Vancomycin tissue concentration measured by high performance liquid chromatography. |
| Acetabulum Vancomycin Level | intraoperative | Intra-operative Acetabulum bone vancomycin concentrations (ug/mL) measured by high performance liquid chromatography. |
| 30-Day Complications | From the administration of antibiotics perioperatively to 30 days post op. | Complications 30 days post surgery eg. infection. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| IV Administration of Vancomycin Standard IV vancomycin administration protocol.
Standard IV administration of vancomycin: IV antibiotics (cefepime & vancomycin) are started in pre-op approximately 1 hour prior to incision (vancomycin dose weight-based at approximately 15mg/kg, generally 1000-1750mg in 500 mL NS). | 10 |
| IO Vancomycin 500mg in 250 mL NS Experimental Intraosseous administration protocol.
Experimental Intraosseous vancomycin 500mg in 250 mL NS: 500mg of Vancomycin in 250 mL of normal saline will be injected into a pre-specified region of the greater trochanter during primary total hip arthroplasty. | 10 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | 1st sample used for calibration of vancomycin tissue/bone concentration | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 2 |
Baseline characteristics
| Characteristic | IV Administration of Vancomycin | IO Vancomycin 500mg in 250 mL NS | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 8 Participants | 15 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 2 Participants | 5 Participants |
| Age, Continuous | 68.51 years STANDARD_DEVIATION 5.99 | 67.89 years STANDARD_DEVIATION 4.1 | 68.31 years STANDARD_DEVIATION 4.81 |
| BMI | 27.36 kg/m^2 STANDARD_DEVIATION 4.68 | 27.85 kg/m^2 STANDARD_DEVIATION 4.88 | 27.6 kg/m^2 STANDARD_DEVIATION 4.66 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 8 Participants | 18 Participants |
| Region of Enrollment United States | 10 participants | 10 participants | 20 participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Male | 8 Participants | 7 Participants | 15 Participants |
| The American Society of Anesthesiologists (ASA) physical status classification | 2.6 units on a scale STANDARD_DEVIATION 0.52 | 2.4 units on a scale STANDARD_DEVIATION 0.52 | 2.5 units on a scale STANDARD_DEVIATION 0.51 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 1 / 10 | 0 / 10 |
| serious Total, serious adverse events | 2 / 10 | 0 / 10 |
Outcome results
Primary
Systemic Vancomycin Level - End of Case
Time frame: end of surgical case
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IV Group | Systemic Vancomycin Level - End of Case | 21 ug/mL | Standard Deviation 7.34 |
| IO Group | Systemic Vancomycin Level - End of Case | 5.75 ug/mL | Standard Deviation 2.86 |
Primary
Systemic Vancomycin Level - Start of Case
vancomycin blood level before the time of incision - typically taken approximately 10 minutes before incision.
Time frame: approximately 10 minutes before incision
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IV Group | Systemic Vancomycin Level - Start of Case | 27.98 ug/mL | Standard Deviation 13.67 |
| IO Group | Systemic Vancomycin Level - Start of Case | 0 ug/mL | Standard Deviation 0 |
Primary
Vancomycin Concentration of Intramedullary Bone
Vancomycin Concentration of Intramedullary Bone in units ug/mL. Vancomycin tissue concentration measured by high performance liquid chromotagraphy.
Time frame: intraoperative
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IV Group | Vancomycin Concentration of Intramedullary Bone | 33.93 ug/mL | Standard Deviation 26.86 |
| IO Group | Vancomycin Concentration of Intramedullary Bone | 59.39 ug/mL | Standard Deviation 28.43 |
Primary
Vancomycin Concentration of Pulvinar Soft Tissue
vancomycin concentration (ug/mL) of pulvinar soft tissue. Vancomycin tissue concentration measured by high performance liquid chromotagraphy.
Time frame: intraoperative
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IV Group | Vancomycin Concentration of Pulvinar Soft Tissue | 61.58 ug/mL | Standard Deviation 46.64 |
| IO Group | Vancomycin Concentration of Pulvinar Soft Tissue | 71.79 ug/mL | Standard Deviation 48.15 |
Secondary
30-Day Complications
Complications 30 days post surgery eg. infection.
Time frame: From the administration of antibiotics perioperatively to 30 days post op.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IV Group | 30-Day Complications | 3 Participants |
| IO Group | 30-Day Complications | 0 Participants |
Secondary
90-Day Complications
Complications 90 days post surgery eg. infection
Time frame: From the administration of antibiotics perioperatively to 90 days post op.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IV Group | 90-Day Complications | 0 Participants |
| IO Group | 90-Day Complications | 0 Participants |
Secondary
Acetabulum Vancomycin Level
Intra-operative Acetabulum bone vancomycin concentrations (ug/mL) measured by high performance liquid chromatography.
Time frame: intraoperative
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IV Group | Acetabulum Vancomycin Level | 67.97 ug/mL | Standard Deviation 24.82 |
| IO Group | Acetabulum Vancomycin Level | 130.88 ug/mL | Standard Deviation 45.4 |
Secondary
Femur Vancomycin Concentration Level
Intraoperative femur bone sample measured for vancomycin concentration (ug/mL). Vancomycin tissue concentration measured by high performance liquid chromatography.
Time frame: intraoperative
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IV Group | Femur Vancomycin Concentration Level | 20.90 ug/mL | Standard Deviation 20.81 |
| IO Group | Femur Vancomycin Concentration Level | 41.45 ug/mL | Standard Deviation 29.92 |
Secondary
Soft Tissue Vancomycin Level - End of Case
soft tissue taken at end of case, right before wound closure is initiated. Vancomycin tissue concentration (ug/mL) measured by high performance liquid chromatography.
Time frame: right before wound closure is initiated at the end of the case
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IV Group | Soft Tissue Vancomycin Level - End of Case | 57.14 ug/mL | Standard Deviation 29.49 |
| IO Group | Soft Tissue Vancomycin Level - End of Case | 78.22 ug/mL | Standard Deviation 26.25 |
Secondary
Soft Tissue Vancomycin Level - Start of Case
at start , soft tissue. Vancomycin tissue concentration (ug/mL) measured by high performance liquid chromatography.
Time frame: at start of case within 15 minutes after incision
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IV Group | Soft Tissue Vancomycin Level - Start of Case | 63.77 ug/mL | Standard Deviation 33.7 |
| IO Group | Soft Tissue Vancomycin Level - Start of Case | 69.08 ug/mL | Standard Deviation 37.48 |