Subcutaneous versus IV piperacillin/tazobactam for adults with serious bacterial infections

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

This study will try whether giving piperacillin/tazobactam under the skin (continuous subcutaneous infusion) produces similar drug levels and safety as the standard IV continuous infusion for adults being treated for serious bacterial infections.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 240 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Azienda Sanitaria Universitaria Friuli Centrale (other)
• Locations: 1 site (Udine, Italia/UD)
• Trial ID: NCT07481539 on ClinicalTrials.gov

What this trial studies

This Phase 2 randomized trial compares continuous subcutaneous infusion of piperacillin/tazobactam with the standard continuous intravenous infusion in adults who require 18 g/day of the drug combination for severe bacterial infections. Participants are randomized to one of the two delivery routes and will have timed blood sampling for pharmacokinetic analysis. Safety, clinical response, and end-of-treatment outcomes will be recorded to determine whether the subcutaneous route is not clinically worse than the IV route. The study focuses on drug exposure, feasibility of subcutaneous administration, and adverse events during the treatment period.

Who should consider this trial

Good fit: Adults aged 18 or older who need piperacillin/tazobactam 18 g/day by continuous infusion for severe bacterial infections (for example severe pneumonia or neutropenic fever) and who can give informed consent are ideal candidates.

Not a fit: Patients who are pregnant, under 18, have infections not susceptible to piperacillin/tazobactam, are hemodynamically unstable requiring immediate IV interventions, or cannot receive subcutaneous infusions are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, subcutaneous piperacillin/tazobactam could enable easier outpatient or home-based treatment, reduce IV line complications, and increase patient convenience.

How similar studies have performed: Subcutaneous delivery of some beta-lactam antibiotics has been used successfully in outpatient settings, but subcutaneous piperacillin/tazobactam is relatively untested, making this approach novel for this drug combination.

Eligibility criteria

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.

Where this trial is running

Udine, Italia/UD

• Azienda Sanitaria Universitaria Friuli Centrale — Udine, Italia/UD, Italy (RECRUITING)

Study contacts

• Principal investigator: Carlo Tascini, Professor — Azienda Sanitaria Universitaria Friuli Centrale
• Study coordinator: Carlo Tascini, Full Professor

Conditions: Bacteria Infection, Piperacillin, Tazobactam Drug Combination, Bacterial Infections, Piperacillin/Tazobactam