Evaluation of the Dialytic Clearance of the Combination of Peracillin and Tazobactam
Trial statusNot yet recruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18+
SponsorUniversity Hospital, Rouen
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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;
Disqualifiers
Documented or suspected allergy to penicillins;
Opposition from the patient or trusted person;
Pregnant, childbirth, or breastfeeding woman;
Minor patient;
Trial 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.
Trial design
Design model
Case-only
Time perspective
Prospective
Treatments tested in this trial
Dosage concentration of piperacillin and tazobactam
Biological/VaccineThe 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.
Treatment groups
No treatment groups listed
Trial outcomes
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.
Time frame
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
1
Determination of EERc clearance of tazobactam
The cERC clearance of tazobactam 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.
Time frame
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)2
Evaluation of total clearance of piperacillin in patients with preserved residual diuresis.
The total clearance (CLT) of piperacillin will be determined by considering that they correspond to the sum of the renal clearance (CLR) and the clearance of the EERc (CLEERc). Thus, CLT = CLR + CLEERc. In the absence of diuresis, CLR=0 will be considered and therefore CLT = CLEERc.
Time frame
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)3
Evaluation of total clearance of tazobactam in patients with preserved residual diuresis.
The total clearance (CLT) of tazobactam will be determined by considering that they correspond to the sum of the renal clearance (CLR) and the clearance of the EERc (CLEERc). Thus, CLT = CLR + CLEERc. In the absence of diuresis, CLR=0 will be considered and therefore CLT = CLEERc.
Time frame
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)4
Description of the evolution of plasma concentrations of piperacillin over time.
Plasma concentrations of piperacillin over time will be evaluated using a population pharmacokinetic model using a nonlinear mixed-effects regression model.
Time frame
At 36 hoursSponsors and contacts
Click on the lead sponsor to view all of their trials.
Source ClinicalTrials.gov
This trial is not recruiting at the moment. You can still explore other options: