Piperacillin-Tazobactam Continuous Versus Intermittent Infusion for Pseudomonas Aeruginosa (PiperTazo)

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

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.

Study Overview

• Status: Completed
• Conditions: Pseudomonas Aeruginosa Infection
• Intervention / Treatment: Drug: Piperacillin-Tazobactam continuous infusion; Drug: Piperacillin-Tazobactam intermittent infusion

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Seville, Spain, 41013
    • Hospital Universitario Virgen del Rocio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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
Mortality		28 days
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
Proportion of patients with adverse effects		14 days & 60 days

Collaborators and Investigators

• Sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
• Collaborators: Hospital Son Espases; Hospital Universitario Virgen Macarena; Hospital Son Llatzer; Hospitales Universitarios Virgen del Rocío; University Hospital Virgen de las Nieves; Hospital Infanta Sofia; Ministerio de Sanidad y Política social; Complejo Hospitalario de Especialidades Juan Ramón Jimenez; Hospital General de Cataluña; Hospital Universitario Ntra. Sra. de La Candelaria

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): January 1, 2014
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: May 16, 2011
• First Submitted That Met QC Criteria: April 12, 2012
• First Posted (Estimate): April 13, 2012

Study Record Updates

• Last Update Posted (Estimate): September 22, 2014
• Last Update Submitted That Met QC Criteria: September 19, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Beta-lactams; Piperacillin; Pseudomonas; Continuous infusion; Intermittent infusion
• Additional Relevant MeSH Terms: Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Pseudomonas Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Piperacillin; Tazobactam; Piperacillin, Tazobactam Drug Combination
• Other Study ID Numbers: PiperTazo; 2010-024606-34 (EudraCT Number)