Comparison of the Effects of Intraosseous and Intravenous Vancomycin Prophylaxis on Surgical Site Infections and Clinical Outcomes After Diabetic Foot Amputation: A Randomized Controlled Trial
Overview
- Phase
- Phase 4
- Status
- Recruiting
- Sponsor
- Başakşehir Çam & Sakura City Hospital
- Enrollment
- 40
- Locations
- 1
- Primary Endpoint
- LOCAL AND SYSTEMIC VANCOMYCIN CONCENTRATIONS
Overview
Brief Summary
he purpose of this study is to compare the effects of two different ways of giving the antibiotic vancomycin to prevent infections in patients undergoing amputation due to diabetic foot infection. Patients with diabetes often have poor blood circulation in their legs, which may prevent standard intravenous (IV) antibiotics from reaching the surgical site in high enough concentrations.
This study compares:
Intraosseous (IO) Administration: Giving the antibiotic directly into the bone at the amputation site during surgery.
Intravenous (IV) Administration: Giving the antibiotic through a standard vein infusion before surgery.
The researchers want to find out if the intraosseous method:
Reduces the rate of surgical site infections compared to the standard IV method.
Causes fewer changes in kidney function (measured by serum creatinine levels). Decreases the need for additional surgeries (reoperations) within 90 days. Patients will be randomly assigned to either the IO or IV group and will be followed for up to 90 days to evaluate their recovery and clinical outcomes
Detailed Description
DETAILED DESCRIPTION THE SURGICAL MANAGEMENT OF DIABETIC FOOT INFECTIONS IS OFTEN COMPLICATED BY PERIPHERAL VASCULAR DISEASE, WHICH SIGNIFICANTLY IMPAIRS THE DELIVERY OF SYSTEMIC PROPHYLACTIC ANTIBIOTICS TO THE INFECTED OR ISCHEMIC EXTREMITY. THIS PROSPECTIVE, RANDOMIZED, CONTROLLED STUDY INVESTIGATES WHETHER INTRAOSSEOUS (IO) ADMINISTRATION OF VANCOMYCIN PROVIDES A SUPERIOR CLINICAL OUTCOME BY DELIVERING HIGHER LOCAL TISSUE CONCENTRATIONS COMPARED TO TRADITIONAL INTRAVENOUS (IV) ADMINISTRATION.
STUDY RATIONALE AND HYPOTHESIS: PREVIOUS STUDIES IN TOTAL KNEE ARTHROPLASTY HAVE SHOWN THAT IO ADMINISTRATION INCREASES LOCAL ANTIBIOTIC TISSUE CONCENTRATION WHILE REDUCING SYSTEMIC LEVELS. DUE TO PERIPHERAL VASCULAR DISEASE IN DIABETIC FOOT PATIENTS, WE BELIEVE THAT SYSTEMICALLY ADMINISTERED VANCOMYCIN (IV) WILL REACH LOWER CONCENTRATIONS AT THE SURGICAL SITE. WE HYPOTHESIZE THAT INTRAOSSEOUS VANCOMYCIN WILL ACHIEVE SIGNIFICANTLY HIGHER DRUG LEVELS IN THE AMPUTATION STUMP AREA, REDUCE THE RATE OF SURGICAL SITE INFECTIONS (SSI), RESULT IN SMALLER INCREASES IN SERUM CREATININE LEVELS DUE TO LOWER SYSTEMIC EXPOSURE, AND DECREASE THE NECESSITY FOR REOPERATION (RTOR) IN PATIENTS UNDERGOING TRANSTIBIAL AMPUTATION.
METHODOLOGY AND INTERVENTIONS: PATIENTS ARE RANDOMIZED IN A 1:1 RATIO INTO TWO TREATMENT ARMS:
IO GROUP: DURING THE AMPUTATION PROCEDURE, 500 MG OF VANCOMYCIN IS ADMINISTERED VIA THE INTRAOSSEOUS ROUTE DIRECTLY AT THE AMPUTATION SITE.
IV GROUP: PATIENTS RECEIVE 500 MG OF VANCOMYCIN INTRAVENOUSLY 15-30 MINUTES PRIOR TO THE SURGICAL INCISION.
PHARMACOKINETIC EVALUATION (PRIMARY FOCUS): VANCOMYCIN CONCENTRATIONS WILL BE MEASURED FROM BOTH THE STUMP SITE (LOCAL TISSUE) AND SYSTEMIC CIRCULATION (PERIPHERAL BLOOD) TO COMPARE THE DISTRIBUTION AND CONCENTRATION GRADIENTS OF THE DRUG BETWEEN THE TWO ADMINISTRATION ROUTES. SAMPLES WILL BE COLLECTED INTRAOPERATIVELY TO DETERMINE IF THE IO ROUTE BYPASSES VASCULAR INSUFFICIENCY.
FOLLOW-UP AND OUTCOME EVALUATION: PATIENTS WILL BE FOLLOWED POSTOPERATIVELY ON DAYS 1,2,3,7 AND 30 FOR CLINICAL OUTCOMES ACCORDING TO CDC CRITERIA. SECONDARY OUTCOMES, INCLUDING SERUM CREATININE LEVELS TO MONITOR RENAL SAFETY AND REOPERATION RATES (REVISION AMPUTATION, DEBRIDEMENT), WILL BE TRACKED FOR UP TO 90 DAYS. MULTIVARIATE LOGISTIC REGRESSION WILL BE USED TO ADJUST FOR CONFOUNDING FACTORS SUCH AS AGE, GENDER, AND HBA1C LEVELS.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Single (Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •PATIENTS AGED 18 YEARS AND OLDER. DIAGNOSED WITH TYPE 1 OR TYPE 2 DIABETES MELLITUS. SCHEDULED FOR TRANSTIBIAL (BELOW-KNEE) AMPUTATION DUE TO DIABETIC FOOT INFECTION.
- •WILLING AND ABLE TO PROVIDE WRITTEN INFORMED CONSENT.
Exclusion Criteria
- •KNOWN ALLERGY OR HYPERSENSITIVITY TO VANCOMYCIN.
- •PRE-EXISTING RENAL INSUFFICIENCY (BASELINE SERUM CREATININE \> 2.0 MG/DL OR GFR \< 30 ML/MIN).
- •PREGNANCY OR BREASTFEEDING.
- •PREVIOUS SURGICAL INTERVENTION OR AMPUTATION ON THE SAME EXTREMITY.
- •BODY MASS INDEX (BMI) OVER
- •CONTRAINDICATION TO STANDARD PROPHYLACTIC ANTIBIOTICS.
- •INABILITY TO LOCALIZE THE TIBIAL TUBERCLE FOR INTRAOSSEOUS INFUSION.
- •IMMUNOCOMPROMISED STATUS (HIV, HEPATITIS C, END-STAGE RENAL DISEASE, DIALYSIS, ACTIVE CHEMOTHERAPY OR RADIOTHERAPY).
- •USE OF IMMUNOSUPPRESSIVE DRUGS WITHIN THE LAST 6 MONTHS.
Arms & Interventions
Intraosseous Vancomycin
500 mg Vancomycin hydrochloride dissolved in of %0.9 NaCl, administered directly into the intramedullary space.
Intervention: Intraosseous Vancomycin (Drug)
Intravenous Vancomycin
500 mg Vancomycin hydrochloride administered via peripheral intravenous infusion
Intervention: Intravenous Vancomycin (Drug)
Outcomes
Primary Outcomes
LOCAL AND SYSTEMIC VANCOMYCIN CONCENTRATIONS
Time Frame: NTRAOPERATIVE (MEASURED DURING SURGERY, APPROXIMATELY 15-30 MINUTES AFTER DRUG ADMINISTRATION).
COMPARISON OF VANCOMYCIN CONCENTRATIONS (MCG/ML) MEASURED FROM THE SURGICAL SITE (LOCAL STUMP AREA) AND THE SYSTEMIC CIRCULATION (PERIPHERAL BLOOD). THE GOAL IS TO EVALUATE THE PHARMACOKINETIC EFFICIENCY OF INTRAOSSEOUS (IO) ADMINISTRATION VERSUS INTRAVENOUS (IV) ADMINISTRATION IN REACHING TARGET LEVELS AT THE AMPUTATION SITE IN PATIENTS WITH PERIPHERAL VASCULAR DISEASE.
Secondary Outcomes
- REOPERATION RATE (RTOR)(UP TO 30 DAYS POSTOPERATIVELY.)
Investigators
Lezgin Mert
Orthopaedic surgeon
Başakşehir Çam & Sakura City Hospital