Evaluation of the Dialytic Clearance of the Combination of Peracillin and Tazobactam

NCT07167524 | Not Yet Recruiting

• 2 other identifiers: 2023/0306/OB2025-A00885-44
• Study Type: observational
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Severe bacterial infections, often responsible for sepsis and septic shock, are a major challenge in critical care: approximately 50% of patients are affected, with a mortality rate of up to 40%. Their initial management consists of antibiotic therapy with an adapted spectrum of activity and dose. One of the most widely used antibiotic therapies in intensive care is the piperacillin-tazobactam (pip-taz) combination, a beta-lactam combined with a beta-lactamase inhibitor, which is indicated probabilistically in many infections (pneumopathies, intra-abdominal infections, urinary tract infections, etc.). Mortality rates of up to 40%. Their initial management consists of antibiotic therapy with an appropriate spectrum of activity and dose. One of the most widely used antibiotic therapies in intensive care is the piperacillin-tazobactam (pip-taz) combination, a beta-lactam combined with a beta-lactamase inhibitor, which is indicated probabilistically in many infections (pneumonia, intra-abdominal infections, urinary tract infections, etc.). Intensive care patients with septic shock exhibit specific pharmacokinetics with an increased volume of distribution, notably due to significant capillary leakage, often disrupted hepatic metabolism, possible hypoalbuminemia, the presence of renal hyperclearance in the initial phase or conversely, the onset of renal failure with altered glomerular filtration rate, sometimes leading to extrarenal clearance, changes that have consequences for the efficacy and toxicity of the administered antibiotic therapy. Sepsis itself also causes renal dysfunction, with the main pathophysiological hypotheses being an alteration of microcirculation, cellular metabolic reprogramming, and deregulation of the inflammatory response. It is therefore essential to focus on the dosages administered and the pharmacokinetics of these patients. Indeed, underdosing is associated with the emergence of resistance and a poorer prognosis in intensive care patients: increased risk of treatment failure, length of stay and mortality. Conversely, significant overdoses can be associated with a poorer renal prognosis, seizures, encephalopathy which can lead to delayed awakening, prolonged duration of mechanical ventilation and intensive care stay.

Conditions

Sepsis; Severe Bacterial Infections

Keywords

medical resuscitation; antibiotic therapy; clearance of piperacillin and tazobactam

Outcome Measures

Primary Outcomes (1)

• Determination of continuous extrarenal clearance (CERC) of piperacillin in patients with infection in intensive care

  The cERC clearance of piperacillin will depend on the type of cERC used, thus determining a clearance: * diffusion (dialysis, continuous venomous hemodialysis (CVVHD)), * convection (filtration, continuous venomous hemofiltration (CVVH)), * diffusion and convection (dialysis and filtration, continuous venomous hemodiafiltration (CVVHDF)). Each of these clearances will be characterized by different formulas, based on the collection of the following parameters: pre- and post-filter concentrations, concentration in the dialysate/filtrate/effluent, cERC flow rate for diffusion and convection, hematocrit, and partition coefficient of the substance between whole blood and plasma.

  At Enrollment visit, Time 15 minutes, 30 minutes and 45 minutes, Time 1 hour, 3 hours, 6 hours, 8 hours, 12 hours, 24 hours and 36 hours in pre-filter (before pre-dilution when present), post-filter (after post-dilution when present)

Secondary Outcomes (6)

• Determination of EERc clearance of tazobactam

  At Enrollment visit, Time 15 minutes, 30 minutes and 45 minutes, Time 1 hour, 3 hours, 6 hours, 8 hours, 12 hours, 24 hours and 36 hours in pre-filter (before pre-dilution when present), post-filter (after post-dilution when present)

• Evaluation of total clearance of piperacillin in patients with preserved residual diuresis.

  At Enrollment visit, Time 15 minutes, 30 minutes and 45 minutes, Time 1 hour, 3 hours, 6 hours, 8 hours, 12 hours, 24 hours and 36 hours in pre-filter (before pre-dilution when present), post-filter (after post-dilution when present)

• Evaluation of total clearance of tazobactam in patients with preserved residual diuresis.

  At Enrollment visit, Time 15 minutes, 30 minutes and 45 minutes, Time 1 hour, 3 hours, 6 hours, 8 hours, 12 hours, 24 hours and 36 hours in pre-filter (before pre-dilution when present), post-filter (after post-dilution when present)

• Description of the evolution of plasma concentrations of piperacillin over time.

  At 36 hours

• Description of the evolution of plasma concentrations of tazobactam over time.

  At 36 hours

Interventions

Dosage concentration of piperacillin and tazobactam BIOLOGICAL

The concentration of piperacillin and tazobactam will be quantified by liquid chromatography coupled with tandem mass spectrometry (HPLC-MS² - CIC-CRB 1404) at each of these times by transposition of the method already used in current practice.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients undergoing continuous extra-renal purification (CER) in the various intensive care units of the Rouen University Hospital (surgical, medical, cardiac surgical), receiving concomitant antibiotic therapy with piperacillin-tazobactam (initiated before or after CER) for sepsis or septic shock.

You may qualify if:

• Adult patient over 18 years of age;
• Patient admitted to intensive care with a prescription for cREV (CVVH (pre- or post-dilution (convection)), CVVHD (diffusion), CVVHDF);
• Diagnosed or suspected infection sensitive to the piperacillin-tazobactam combination administered by continuous infusion as part of the patient's standard care;
• Concomitant prescription of piperacillin-tazobactam and cREV;
• Patient affiliated with a social security scheme;
• Adult who has read and understood the information letter and has not expressed non-opposition. Due to the potential life-threatening emergency, if the patient is unable to express their non-opposition, the consent of a trusted person or, where applicable, relatives will be sought.

You may not qualify if:

• Documented or suspected allergy to penicillins;
• Opposition from the patient or trusted person;
• Pregnant, childbirth, or breastfeeding woman;
• Minor patient;
• Person deprived of liberty by an administrative or judicial decision;
• Person placed under judicial protection, guardianship, or curatorship.

Sponsors & Collaborators

• University Hospital, Rouen: lead

Study Sites (1)

University Rouen Hospital

Rouen, 76031, France

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples will be collected at baseline, T15min, T30min, T45min, T1h, T3h, T6h, T8h, T12h, T24h, T36h in pre-filter (before pre-dilution when present), post-filter (after post-dilution when present), in the effluent and in the urine in case of preserved diuresis. Biological samples will be collected in EDTA tubes with a capacity of 2mL.

MeSH Terms

Conditions

Sepsis; Bacterial Infections

Interventions

Tazobactam

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bacterial Infections and Mycoses

Intervention Hierarchy (Ancestors)

Penicillanic Acid; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Sulfones; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Central Study Contacts

Camille CR RENARD, Doctor

CONTACT

02 32 88 33 27; Domitille.Renard@chu-rouen.fr

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2025
• First Posted: September 11, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): April 1, 2028
• Last Updated: September 11, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)