Does Intraosseous Compared With Intravenous Vancomycin Alter Local Exposure, Systemic Safety, and Early Outcomes in Patients With Ischemic Diabetic Foot Undergoing Below-knee Amputation? A Randomized Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Subcutaneous Soft-Tissue Vancomycin Concentration (mcg/g)
研究概览
简要总结
This randomized clinical trial compared two routes of vancomycin administration in patients undergoing below-knee amputation for ischemic diabetic foot infection. Patients with diabetic foot infection and impaired lower-extremity circulation may have reduced delivery of intravenously administered antibiotics to the amputation stump. Intraosseous administration may increase local antibiotic exposure at the surgical site while reducing systemic exposure.
Participants were randomly assigned to receive either intraosseous vancomycin or intravenous vancomycin before skin incision. The study evaluated vancomycin concentrations in amputation stump subcutaneous tissue, simultaneous serum vancomycin concentrations, tissue-to-serum concentration ratios, inflammatory marker trajectories, early wound outcomes, pain scores, drain output, reintervention, mortality, renal safety, and systemic adverse events through postoperative follow-up.
详细描述
Patients with diabetic foot infection and distal ischemia scheduled for below-knee amputation were evaluated by a multidisciplinary diabetic foot council. Eligible patients were randomized in a 1:1 ratio to receive either intraosseous or intravenous vancomycin before skin incision.
In the intraosseous group, 500 mg of vancomycin diluted in 100 mL of normal saline was administered into the proximal tibial metaphysis using a sterile intraosseous vascular access system immediately before skin incision. In the intravenous group, 500 mg of vancomycin was administered intravenously at the same preincision time point. No tourniquet was used.
During surgery, a subcutaneous soft-tissue sample was obtained from the planned amputation stump region, and a simultaneous venous serum sample was collected. Vancomycin concentrations were measured in both samples. The primary pharmacokinetic outcomes were stump subcutaneous soft-tissue vancomycin concentration, serum vancomycin concentration, tissue-to-serum concentration ratio.
Secondary outcomes included postoperative trajectories of white blood cell count, C-reactive protein, procalcitonin, and interleukin-6; early postoperative pain scores; total drain output during the first 24 hours; early wound-healing outcomes assessed using ASEPSIS scores; surgical reintervention; mortality; renal safety outcomes based on serum creatinine; and systemic adverse events including vancomycin infusion reaction, allergic reaction, symptomatic deep vein thrombosis, and pulmonary embolism.
Clarification of Registry Updates
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Outcomes Assessor)
盲法说明
Because the route of vancomycin administration was apparent during surgery, the operating surgeon and operating room personnel were not blinded to group allocation. Laboratory personnel who measured vancomycin concentrations were blinded to treatment allocation. Postoperative clinical outcomes were recorded by a blinded assessor using predefined criteria; however, final clinical endpoint evaluation was not fully blinded because the study team included the operating surgeons.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 years or older
- •Diagnosis of diabetes mellitus
- •Diabetic foot infection with distal ischemia
- •Scheduled to undergo below-knee amputation
- •Absence of a feasible further revascularization option, as determined by the cardiovascular surgery and interventional radiology teams
- •Adequate circulation at and proximal to the planned below-knee amputation level for stump healing
- •Ability to provide written informed consent
排除标准
- •Documented allergy or hypersensitivity to vancomycin or cephalosporins
- •Dialysis dependence
- •Systemic vancomycin use within 48 hours before surgery
- •Previous Syme amputation or more proximal amputation
- •Planned amputation at a level other than below the knee
- •Incomplete perioperative pharmacokinetic sampling
研究组 & 干预措施
Intravenous Vancomycin
Participants received 500 mg of vancomycin intravenously at the same preincision time point before below-knee amputation.
干预措施: Intravenous Vancomycin (Drug)
Intraosseous Vancomycin
Participants received 500 mg of vancomycin diluted in 100 mL of 0.9% normal saline via intraosseous administration into the proximal tibial metaphysis immediately before skin incision.
干预措施: Intraosseous Vancomycin (Drug)
结局指标
主要结局
Subcutaneous Soft-Tissue Vancomycin Concentration (mcg/g)
时间窗: Perioperatively, during below-knee amputation
Vancomycin concentration in intraoperative stump subcutaneous tissue, measured by institutional laboratory assay.
Serum Vancomycin Concentration (mcg/mL)
时间窗: Perioperatively, during below-knee amputation
Vancomycin concentration in simultaneous venous serum, measured by institutional laboratory assay.
Tissue-to-Serum Vancomycin Concentration Ratio
时间窗: Perioperatively, during below-knee amputation
Ratio calculated by dividing stump subcutaneous tissue vancomycin concentration by simultaneous serum vancomycin concentration.
Participants With Stump Tissue Vancomycin Concentration ≥16 mcg/g
时间窗: Perioperatively, during below-knee amputation
Number of participants with intraoperative stump subcutaneous tissue vancomycin concentration ≥16 mcg/g.
LOCAL AND SYSTEMIC VANCOMYCIN CONCENTRATIONS
时间窗: 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.
次要结局
- White Blood Cell Count (10^3/uL)(Preoperative, postoperative 12 hours, postoperative day 1, day 3, day 7, and day 30)
- C-Reactive Protein Concentration (mg/L)(Preoperative, postoperative 12 hours, postoperative day 1, day 3, day 7, and day 30)
- Procalcitonin Concentration (ng/mL)(Preoperative, postoperative day 1, day 3, day 7, and day 30)
- Interleukin-6 Concentration (pg/mL)(Preoperative, postoperative day 1, day 3, day 7, and day 30)
- Total Drain Output (mL)(From postoperative day 0 to postoperative day 1)
- Participants With ASEPSIS Score >20(Through postoperative day 7)
- Visual Analog Scale Pain Score(Postoperative 6 hours, 24 hours, and day 3)
- Peak ASEPSIS Wound Score(Through postoperative day 7)
- REOPERATION RATE (RTOR)(UP TO 30 DAYS POSTOPERATIVELY.)
研究者
Lezgin Mert
Orthopaedic surgeon
Başakşehir Çam & Sakura City Hospital