Prolonged Infusion Cefepime and Nosocomial Infections (PICNIC)

It is advocated that prolonged infusion of beta-lactamic antibiotics provides better bactericidal effect. The aim of the present study is to randomize patients a to extended cefepime infusion regimen (lasting four hours) or to a usual infusion regimen (not lasting more than thirty minutes) and evaluate the clinical efficacy of this theoretical pharmacokinetic advantage.

Study Overview

• Status: Unknown
• Conditions: Urinary Tract Infection; Respiratory Tract Infection
• Intervention / Treatment: Drug: Prolonged Cefepime Infusion; Drug: Usual Cefepime Infusion

Detailed Description

Introduction: it has been proved that the main determinant for microbiological cure gram-negative infections treated with cefepime is the time above minimal inhibitory concentration (T>MIC). Although this particular pharmacokinetic property have never been proved in clinical trials utilizing cefepime, intervention studies with other betalactamic antibiotics, such as pipercillin-tazobactam, showed clinical benefit.

Objective: to evaluate if prolonged infusion (lasting 4 hours) with cefepime translate into better clinical outcomes.

Methods: the investigators aim to conduct an open-label, unique-centered, randomized controlled trial using cefepime in prolonged infusions in patients being treated for urinary or respiratory tract infections. Patients developing these infections after 72 hours of hospital admission, requiring the use of broader spectrum antibiotics after clinical failure or isolating gram-negative bacteria from adequate sample sensible to cefepime will be enrolled. The use of a second antibiotic such as clindamycin, vancomycin or metronidazole will be allowed.

Interventions: the investigators aim to randomize 134 patients to two different treatment arms, the intervention arm who will receive the medication in a four hour lasting infusion, and the active control arm who will receive the medication in a 30 minutes lasting infusion. The randomization will be conducted in blocks of ten patients each, and it will be balance according to the patients age (older or younger than 65 years old) and presence of SIRS criteria.

• Study Type: Interventional
• Enrollment (Anticipated): 134
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: André Dias Américo; Phone Number: +555193112207; Email: adamerico@hcpa.edu.br

Study Locations

• Brazil
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil
      • Recruiting
      • Hospital de Clínicas de Porto Alegre
      • Contact: André Dias Américo; Phone Number: +555133598152; Email: adamerico@hcpa.edu.br

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Urinary tract infection after 48-72 hours of hospital stay
• Respiratory tract infection after 48-72 hours of hospital stay
• Catheter related urinary tract infection after 48-72 hours of hospital stay
• Urinary or respiratory infections not responding to a narrower spectrum antibiotic
• Isolation of bacteria sensible to cefepime in blood, urine or sputum in a clinical context of infection

Exclusion Criteria:

• Glomerular filtration rate lower than 30 ml.min/1,73m²
• ICU admission for at least 72 hours before randomization
• Neutrophil count lower than 1000 cels per mm³
• Hematologic malignancy, bronchiectasis and cystic fibrosis
• Patients allergic to cefepime
• Concomitant treatment to another infectious disease
• Central nervous system, cutaneous or intrabdominal infections
• Solid organ transplantation
• HIV with a cluster differentiation 4 (CD4) lower than 100 cels per mm³

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prolonged Cefepime Infusion; Cefepime infusions should last 4 hours at least	Drug: Prolonged Cefepime Infusion; Cefepime infusion should last at least 4 hours with the aide of an infusion bomb; Other Names: Estended Cefepime Infusion
Active Comparator: Usual Cefepime Infusion; Cefepime infusion should last no more than 30 minutes	Drug: Usual Cefepime Infusion; Cefepime infusion occurs directly without the aide of an infusion bomb, lasting roughly thirty minutes; Other Names: Regular Cefepime Infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death	Death in 30 days since randomization	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death	Death in 14 days since randomization	14 days
Duration of hospital stay	Duration of hospital stay	30 days since randomization
Intensive care unit (ICU) admission	Intensive care necessity for any reason	30 days since randomization
Duration of intensive care unit (ICU) stay	Number of days when intensive care was considered necessary	30 days since randomization
Treatment change	Treatment change required based com clinical or microbiological data	3 days after randomization
Treatment success	Patient reaching the completion until it end with infection resolution	30 days since randomization
Time to clinical stability	Time required for patient to reach the normalization of all following vital signs: that is, body temperature lower than 37,9 degrees celsius, a cardiac rate lower than 100 beats per minute and a respiratory rate lower than 25 respiratory movements per minute and peripheral oxygen saturation higher than 91% with low oxygen requirement (that is 4 liters per minute delivered by nasal canula)	3 days

Collaborators and Investigators

• Sponsor: Hospital de Clinicas de Porto Alegre
• Investigators: Principal Investigator: Eduardo Sprinz, Hospita de Clínicas de Porto Alegre

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (Anticipated): March 1, 2016
• Study Completion (Anticipated): September 1, 2016

Study Registration Dates

• First Submitted: October 2, 2015
• First Submitted That Met QC Criteria: October 5, 2015
• First Posted (Estimate): October 6, 2015

Study Record Updates

• Last Update Posted (Estimate): October 16, 2015
• Last Update Submitted That Met QC Criteria: October 15, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Urologic Diseases; Disease Attributes; Iatrogenic Disease; Infections; Communicable Diseases; Urinary Tract Infections; Respiratory Tract Infections; Cross Infection; Anti-Infective Agents; Anti-Bacterial Agents; Cefepime
• Other Study ID Numbers: 15-0392