Standard Versus Pre-emptive Antibiotic Treatment to Reduce the Rate of Infectious Outcomes After Whipple's Procedure (SPARROW): a Multicenter, Randomized Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 344
- 试验地点
- 11
- 主要终点
- Rate of clinically relevant organ/space surgical site infection (OSI) between patients with perioperative versus prolonged antibiotic prophylaxis
研究概览
简要总结
The goal of this multicenter randomized controlled trial is to evaluate the additional value of pre-emptive antibiotic treatment on clinically relevant organ/space surgical site infections (OSIs) in patients undergoing pancreatoduodenectomy with a high risk for contaminated bile. The main objectives it aims to answer are:
- To evaluate the effect of pre-emptive antibiotic prophylaxis on clinically relevant OSIs in patients undergoing pancreatoduodenectomy with a high risk for contaminated bile
- To evaluate the effect of pre-emptive antibiotic prophylaxis on other postoperative outcomes (e.g. OSIs, superficial SSIs, POPF, PPH, major morbidity, ICU admission, readmission, length of hospital stay, and mortality).
- To evaluate concordance between perioperatively obtained bile cultures and postoperative cultures from infectious sites, and to evaluate antibiotic sensitivity patterns of the cultured microorganisms.
Participants will be randomized with a 1:1 allocation before surgery into the intervention or control group:
- Patients in the intervention group will receive perioperative prophylaxis (similar to the control group) followed by five days of 1500mg IV cefuroxime and 500mg IV metronidazole thrice daily.
- Patients in the control group will only receive perioperative prophylaxis (a single dose of 5-7mg/kg gentamicin followed by 2gr IV cefazolin and 500mg IV metronidazole every 4h of surgery), which will be discontinued after surgery.
详细描述
Rationale: The additional value of pre-emptive antibiotic treatment after pancreatoduodenectomy is undetermined as previous research reported conflicting results regarding infectious complications. Prolonged antibiotic prophylaxis (formally pre-emptive antibiotic treatment) after pancreatoduodenectomy might reduce the rate of surgical site infections in patients with a high risk for contaminated bile (predominantly patients with preoperative biliary drainage or an ampullary malignancy). Current national and international guidelines lack clear recommendations regarding pre-emptive antibiotic treatment leading to substantially varying antibiotic prophylactic regimes between institutes.
Objective: This trial evaluates the additional value of pre-emptive antibiotic treatment on clinically relevant organ/space surgical site infections (OSIs) in patients undergoing pancreatoduodenectomy with a high risk for contaminated bile.
Study design: This multicenter, randomized controlled, superiority trial compares perioperative versus pre-emptive antibiotic treatment during five postoperative days after pancreatoduodenectomy in patients with a high risk for contaminated bile.
Study population: Adult patients undergoing pancreatoduodenectomy with a high risk for contaminated bile (patients with preoperative biliary drainage or an ampullary malignancy). Patients with a contraindication for the study antibiotics or a preoperative indication for antibiotics (e.g. cholangitis of preoperative abscesses) are excluded.
Intervention: Participants will be randomized to either perioperative prophylaxis (cefazolin, metronidazole and a single dose of 5-7mg/kg gentamicin, control arm) or additional cefuroxime and metronidazole for five postoperative days (experimental arm).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients undergoing elective pancreatoduodenectomy with a high risk for contaminated bile defined as patients with preoperative biliary drainage or an ampullary malignancy.
- •Age >18 years
排除标准
- •Pregnancy
- •Contraindication for the study antibiotics (e.g. allergy or intolerance)
- •Preoperative planned therapeutic antibiotic treatment (i.e. for cholangitis or liver abscesses)
- •A reduced renal function, defined as an eGFR of <60 ml/min/1.73m2 measured on the closest timepoint prior to pancreatoduodenectomy
研究组 & 干预措施
Perioperative plus prolonged antibiotic prophylaxis
Prolonged prophylaxis: a single dose of 5-7mg/kg gentamicin followed by 2gr IV cefazolin and 500mg IV metronidazole every 4 hours of surgery (perioperative prophylaxis) followed by five days of 1500mg IV cefuroxime and 500mg IV metronidazole thrice daily
干预措施: Cefuroxime (Drug)
Perioperative plus prolonged antibiotic prophylaxis
Prolonged prophylaxis: a single dose of 5-7mg/kg gentamicin followed by 2gr IV cefazolin and 500mg IV metronidazole every 4 hours of surgery (perioperative prophylaxis) followed by five days of 1500mg IV cefuroxime and 500mg IV metronidazole thrice daily
干预措施: Metronidazole (Drug)
结局指标
主要结局
Rate of clinically relevant organ/space surgical site infection (OSI) between patients with perioperative versus prolonged antibiotic prophylaxis
时间窗: 90 days after surgery
A clinically relevant OSI is defined by the following criteria: * A deep surgical site infection involving any part of the abdomen (e.g. organs and/or spaces) other than the surgical incision within 90 days after surgery. * AND Requires radiological, endoscopic or surgical intervention OR therapeutic antibiotics required for an episode of sepsis, defined as two or more SIRS criteria. * AND Organisms isolated from an aseptically obtained culture.
次要结局
- The number of reinterventions in patients with perioperative versus prolonged antibiotic prophylaxis(90 days)
- The number of ICU admission in patients with perioperative versus prolonged antibiotic prophylaxis(90 days)
- Mortality(90 days)
- The rate of organ/Space Infection (OSI) between patients with perioperative versus prolonged antibiotic prophylaxis(90 days)
- The rate of postoperative bacteremia between patients with perioperative versus prolonged antibiotic prophylaxis(90 days)
- Length of hospital stay in patients with perioperative versus prolonged antibiotic prophylaxis(90 days)
- The rate of isolated OSI between patients with perioperative versus prolonged antibiotic prophylaxis(90 days)
- The rate of clinically relevant postoperative pancreatic fistula between patients with perioperative versus prolonged antibiotic prophylaxis(90 days)
- The rate of bile leakage between patients with perioperative versus prolonged antibiotic prophylaxis(90 days)
- The rate of post pancreatectomy hemorrhage between patients with perioperative versus prolonged antibiotic prophylaxis(90 days)
- The rate of delayed gastric emptying between patients with perioperative versus prolonged antibiotic prophylaxis(90 days)
- Rate of major complications between patients with perioperative versus prolonged antibiotic prophylaxis(90 days)
- The rate of superficial incisional SSI between patients with perioperative versus prolonged antibiotic prophylaxis(90 days)
- The rate of Clostridium difficile infection between patients with perioperative versus prolonged antibiotic prophylaxis(90 days)
- The number of readmissions between patients with perioperative versus prolonged antibiotic prophylaxis(90 days)
研究者
J.S.D. Mieog, MD PhD
Principal Investigator
Leiden University Medical Center