Subcutaneous Piperacillin/Tazobactam Compared With Intravenous Treatment (STUPITA01)

Evaluation of the Pharmacokinetics of Subcutaneous Administration of Piperacillin/Tazobactam: an Open-Label, Multicentric, Non-inferiority Randomized Clinical Trial

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

Study Overview

• Status: Recruiting
• Conditions: Piperacillin, Tazobactam Drug Combination; Bacteria Infection
• Intervention / Treatment: Device: Piperacillin, Tazobactam Drug Combination; Drug: Piperacillin, Tazobactam Drug Combination

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Carlo Tascini, Full Professor; Phone Number: +39-0432-559355; Email: carlo.tascini@uniud.it
• Study Contact Backup: Name: Chiara Moreal, MSn RN; Phone Number: +39-339-4091948; Email: moreal.chiara@spes.uniud.it

Study Locations

• Italy
  • Italia/UD
    • Udine, Italia/UD, Italy, 33100
      • Recruiting
      • Azienda Sanitaria Universitaria Friuli Centrale
      • Contact: Carlo Tascini, Professor; Phone Number: +39-0432-559355; Email: carlo.tascini@uniud.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Device: Piperacillin, Tazobactam Drug Combination; 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.; Other Names: Piperacillin and tazobactam; Drug: Piperacillin, Tazobactam Drug Combination; 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.
Active Comparator: 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	Device: Piperacillin, Tazobactam Drug Combination; 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.; Other Names: Piperacillin and tazobactam; Drug: Piperacillin, Tazobactam Drug Combination; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK profile	Area under the plasma concentration-time curve (AUC) of piperacillin/tazobactam measured from plasma antibiotic concentrations collected for pharmacokinetic assessment at steady state.	Day 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Achieving target concentrations	Proportion of participants achieving the prespecified target piperacillin plasma concentration of at least 40 mg/L based on therapeutic drug monitoring and pharmacokinetic/pharmacodynamic criteria.	Days 0, 1, 3, and 6
Clinical cure at end of treatment	Clinical cure rate at the end of treatment, defined as partial or complete resolution of baseline clinical signs and symptoms of infection without need for additional antibiotic therapy for the index infection.	Day 8
Incidence of local and systemic adverse events	Incidence of local adverse events related to the administration route (including edema, pain, erythema, and necrosis) and systemic adverse events recorded during treatment.	Up to Day 9
Health-related quality of life assessed by EQ-5D-5L	Health-related quality of life assessed with the EuroQol 5 Dimensions 5 Levels questionnaire (EQ-5D-5L). The EQ-5D-5L descriptive system includes 5 dimensions scored on 5 levels from 1 to 5; lower levels indicate better health status. Participants also complete the EQ Visual Analogue Scale (EQ VAS), ranging from 0 to 100, where higher scores indicate better perceived health.	Days 0, 3, and 9
Patient-reported experience assessed by PREM questionnaire	Patient-reported experience assessed using the study PREM questionnaire.	Day 9
Perception of nurses	Nurses' perceptions of subcutaneous versus intravenous administration of piperacillin/tazobactam explored through semi-structured interviews addressing ease of administration, perceived benefits and challenges, patient responses, and logistical or technical issues.	Through study completion

Collaborators and Investigators

• Sponsor: Azienda Sanitaria Universitaria Friuli Centrale
• Investigators: Principal Investigator: Carlo Tascini, Professor, Azienda Sanitaria Universitaria Friuli Centrale

Study record dates

Study Major Dates

• Study Start (Estimated): March 24, 2026
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): April 30, 2027

Study Registration Dates

• First Submitted: March 9, 2026
• First Submitted That Met QC Criteria: March 16, 2026
• First Posted (Actual): March 19, 2026

Study Record Updates

• Last Update Posted (Actual): March 19, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Bacterial Infections; Piperacillin/Tazobactam
• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Bacterial Infections; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pharmaceutical Preparations; Amides; Drug Combinations; Penicillin G; beta-Lactams; Lactams; Sulfones; Tazobactam; Penicillanic Acid; Piperacillin; Ampicillin; Penicillins; Piperacillin, Tazobactam Drug Combination
• Other Study ID Numbers: 2024-519663-17-01 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No