Piperacillin-Tazobactam Continuous Versus Intermittent Infusion for Pseudomonas Aeruginosa

Study Overview
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Brief Summary
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The main objective is to verify that the administration of piperacillin / tazobactam administered by continuous infusion to treat complicated infections or with known or suspected nosocomial isolation of Pseudomonas aeruginosa is superior in efficacy to a 30% higher dose administered in conventional short infusion. The secondary objectives were compared between the following variables: Microbiological response at 3 days of starting treatment Time to microbiological cure Clinical response at 3 days of starting treatment Time to achieve defervescence To examine the relationship between pharmacokinetic variables and parameters of efficacy and safety To test the hypothesis that continuous infusion maintains adequate plasma drug levels compared with levels achieved with intermittent administration. Cost-effectiveness analysis Occurrence of adverse effects To this end, we designed a multicenter, randomized, controlled, double blind, comparing both forms of administration in patients with complicated or nosocomial infection with or without isolation of Pseudomonas aeruginosa. Patients who are candidates for inclusion are classified according to APACHE II and to have or not isolation of Pseudomonas aeruginosa. Subsequently be randomized to receive piperacillin-tazobactam by continuous infusion or short. Primary endpoint was measured as the ultimate effectiveness of treatment and other variables such as high efficiency, safety, pharmacokinetic and pharmacoeconomic.

Official Title
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Efficacy and Safety of Piperacillin-Tazobactam Continuous Infusion vs Intermittent Infusion for Complicated or Nosocomial Pseudomonas Aeruginosa Infection or Suspected Infection

Conditions
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Pseudomonas Aeruginosa Infection

Intervention / Treatment
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* Drug: Piperacillin-Tazobactam continuous infusion
* Drug: Piperacillin-Tazobactam intermittent infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Complicated or Nosocomial Pseudomonas Aeruginosa Infection or Suspected Infection > 18 years and > 40 kg Negative pregnancy test for women within fertile period Informed consent signature Exclusion Criteria: Life expectancy < 72 hr Central Nervous System (CNS) infection Ventilator-associated pneumonia Severe Neutropenia (<500 cells/ml) Acinetobacter baumannii or extended spectrum beta lactamase (ESBL) suspected infection Cystic fibrosis Shock Creatinine clearance < 20 ml/min Dialysis or hemoperfusion

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Piperacillin continuous infusion<br>Piperacillin-Tazobactam 2gr (Loading dose DAY 1) plus Piperacillin-Tazobactam continuous infusion 8gr every 24 hours | Drug: Piperacillin-Tazobactam continuous infusion<br>* Piperacillin-Tazobactam 2gr (Loading dose DAY 1) plus Piperacillin-Tazobactam continuous infusion 8gr every 24 hours (DAY 1-14)<br>|
| Active Comparator: Piperacillin intermittent infusion<br>Piperacillin-Tazobactam 4gr intermittent infusion 4gr every 8 hours | Drug: Piperacillin-Tazobactam intermittent infusion<br>* Piperacillin-Tazobactam intermittent infusion 4gr every 8 hours (DAY 1-14)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with satisfactory clinical response (cure or improvement) at the end of Piperacillin-Tazobactam treatment | Clinical cure: complete resolution of all signs and symptoms of infection Clinical improvement: resolution or improvement of most signs and symptoms of infection | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with clinical response (cure or improvement) at 3 days | Clinical cure: complete resolution of all signs and symptoms of infection Clinical improvement: resolution or improvement of most signs and symptoms of infection | 3 days | 
| Proportion of patients with microbiological response | - Microbiological response: bacteriological eradication of causative organisms | 3 days | 
| Time to defervescence | - Time to the abatement of fever | 14 days | 
| Time to clinical cure |  | 14 days | 
| Mortality |  | 28 days | 
| Proportion of patients with adverse effects |  | 14 days & 60 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pseudomonas, Piperacillin, Beta-lactams, Continuous infusion, Intermittent infusion, Pharmacokinetics