Evaluation of the Pharmacokinetics of Subcutaneous Administration of Piperacillin/Tazobactam: an Open-Label, Multicentric, Non-inferiority Randomized Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 240
- 试验地点
- 1
- 主要终点
- PK profile
研究概览
简要总结
The goal of this clinical trial is to learn whether subcutaneous piperacillin/tazobactam can provide drug exposure similar to standard intravenous piperacillin/tazobactam in adults who need treatment for an infection. It will also assess safety and clinical outcomes. The main questions it aims to answer are:
- Does subcutaneous piperacillin/tazobactam achieve pharmacokinetic exposure comparable to intravenous treatment?
- Is subcutaneous piperacillin/tazobactam safe and feasible in this population? Researchers will compare subcutaneous continuous infusion with intravenous continuous infusion to see whether the subcutaneous route is not clinically worse than the standard intravenous route.
Participants will:
- Receive piperacillin/tazobactam by subcutaneous or intravenous continuous infusion after randomization
- Have blood samples collected for pharmacokinetic assessments
- Undergo safety, clinical, and end-of-treatment assessments during the study period
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Free, written and informed consent signed by the participant;
- •At least 18 years old on the day of inclusion;
- •Male and female participants;
- •Clinical indication for treatment with piperacillin/tazobactam 18g/die in continuous infusion, including severe pneumonia, neutropenic fever suspected to be caused by bacterial infection or other severe bacterial infections for which, based on investigator's judgment, this dosage regimen is appropriate;
- •Evidence of postmenopausal status, defined as no menses for at least 12 consecutive months without an alternative medical cause and, if clinically indicated, confirmed by serum FSH levels in the postmenopausal range; or Negative serum pregnancy test at the screening visit (sensitivity ≥25 mIU/mL) and negative urine β-HCG test at the End-of-Treatment (D8) for females of childbearing potential who are sexually active with a non-sterilized male partner.
- •Women of childbearing potential (WOCBP) are defined as all women who are not surgically sterile (bilateral salpingectomy, bilateral oophorectomy, or complete hysterectomy) and who are not postmenopausal;
- •- Admitted to one of the wards authorized for the enrollment.
排除标准
- •Known hypersensitivity to penicillins, cephalosporins, other β-lactamase inhibitors, or any component of the formulation;
- •Pregnant or breastfeeding women, and women intending to become pregnant during the study or within the End-of-Treatment visit;
- •Women of childbearing potential (WOCBP) unwilling or unable to use at least one highly effective method of contraception, as defined in Section 7.4, throughout study participation and for at least at the End-of-Treatment visit;
- •No indication for treatment with TZP;
- •Known resistance to TZP;
- •Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications;
- •Participation in another clinical trial with administration of an investigational medicinal product (IMP) within 30 days prior to screening or within 5 half-lives of that IMP, whichever is longer.
研究组 & 干预措施
SC ARM
Participants randomized to the experimental arm will receive piperacillin/tazobactam by continuous subcutaneous infusion from D1 to D7 (end at D8), at a total daily dose of 18 g/day, administered via syringe pump. The study drug will be prepared every 12 hours as 9 g in 40 mL of 0.9% sodium chloride in a polypropylene syringe and infused through a small subcutaneous cannula (22-24G). Preferred insertion sites are the abdomen, followed by the thigh or arm. Cannula insertion and management will follow aseptic no-touch technique, with site change only if clinically indicated based on patient comfort or local site findings. Renal dose adjustments will be applied according to protocol.
干预措施: Piperacillin, Tazobactam Drug Combination (Device)
SC ARM
Participants randomized to the experimental arm will receive piperacillin/tazobactam by continuous subcutaneous infusion from D1 to D7 (end at D8), at a total daily dose of 18 g/day, administered via syringe pump. The study drug will be prepared every 12 hours as 9 g in 40 mL of 0.9% sodium chloride in a polypropylene syringe and infused through a small subcutaneous cannula (22-24G). Preferred insertion sites are the abdomen, followed by the thigh or arm. Cannula insertion and management will follow aseptic no-touch technique, with site change only if clinically indicated based on patient comfort or local site findings. Renal dose adjustments will be applied according to protocol.
干预措施: Piperacillin, Tazobactam Drug Combination (Drug)
IV ARM
Participants randomized to the control arm will receive piperacillin/tazobactam by continuous intravenous infusion from D1 to D7 (end at D8), at a total daily dose of 18 g/day. The study drug will be prepared every 24 hours as 18 g in 500 mL of 0.9% sodium chloride and administered through an electronic infusion pump using a dedicated intravenous line. Intravenous access may be peripheral or central, according to clinical practice and local requirements. Infusion line management and site care will follow local aseptic procedures and institutional standards. Renal dose adjustments will be applied according to protocol
干预措施: Piperacillin, Tazobactam Drug Combination (Device)
IV ARM
Participants randomized to the control arm will receive piperacillin/tazobactam by continuous intravenous infusion from D1 to D7 (end at D8), at a total daily dose of 18 g/day. The study drug will be prepared every 24 hours as 18 g in 500 mL of 0.9% sodium chloride and administered through an electronic infusion pump using a dedicated intravenous line. Intravenous access may be peripheral or central, according to clinical practice and local requirements. Infusion line management and site care will follow local aseptic procedures and institutional standards. Renal dose adjustments will be applied according to protocol
干预措施: Piperacillin, Tazobactam Drug Combination (Drug)
结局指标
主要结局
PK profile
时间窗: Day 3
Area under the plasma concentration-time curve (AUC) of piperacillin/tazobactam measured from plasma antibiotic concentrations collected for pharmacokinetic assessment at steady state.
次要结局
- Achieving target concentrations(Days 0, 1, 3, and 6)
- Clinical cure at end of treatment(Day 8)
- Incidence of local and systemic adverse events(Up to Day 9)
- Health-related quality of life assessed by EQ-5D-5L(Days 0, 3, and 9)
- Patient-reported experience assessed by PREM questionnaire(Day 9)
- Perception of nurses(Through study completion)
研究者
carlo.tascini@uniud.it
Full Professor
Azienda Sanitaria Universitaria Friuli Centrale