Clinical trial NCT02568800: Prolonged Infusion Cefepime and Nosocomial Infections
Official title: Prolonged Infusion Cefepime and Nosocomial Infections
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Urinary Tract Infection
Respiratory Tract Infection
Lead sponsor: Hospital de Clinicas de Porto Alegre
Sponsor class: OTHER
First posted: 2015-10-06
Enrollment: 134
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Death
timeFrame: 30 days
Secondary outcomes:
measure: Death
timeFrame: 14 days
measure: Duration of hospital stay
timeFrame: 30 days since randomization
measure: Intensive care unit (ICU) admission
timeFrame: 30 days since randomization
measure: Duration of intensive care unit (ICU) stay
timeFrame: 30 days since randomization
measure: Treatment change
timeFrame: 3 days after randomization
measure: Treatment success
timeFrame: 30 days since randomization
measure: Time to clinical stability
timeFrame: 3 days
Other outcomes:
Locations:
city: Porto Alegre
country: Brazil
facility: Hospital de Clínicas de Porto Alegre
state: Rio Grande do Sul
Study officials:
affiliation: Hospita de Clínicas de Porto Alegre
name: Eduardo Sprinz
role: PRINCIPAL_INVESTIGATOR
References: