Clinical trial NCT00934011: Use of Inflammatory Biomarkers to Guide Antibiotic Therapy in Patients With Severe Infections
Official title: Comparative Study of C-reactive Protein vs. Procalcitonin to Guide Antibiotic Therapy in Patients With Severe Sepsis and Septic Shock Admitted to the Intensive Care Unit.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Severe Sepsis
Septic Shock
Keywords: C-reactive protein
procalcitonin
sepsis
antibiotic therapy
Lead sponsor: Federal University of Minas Gerais
Sponsor class: OTHER
Collaborators: name: Fundação de Amparo à Pesquisa do estado de Minas Gerais
First posted: 2009-07-08
Enrollment: 94
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In this study the investigators aim to test if C-reactive protein (CRP)or procalcitonin(PCT) - guided strategy allows to reduce the antibiotic use in patients wiht severe sepsis and septic shock. Therefore, the safety of this intervention will be carefully measured.

Detailed description: Methods

* Patients and settings: Prospective controlled randomized open interventional study of antibiotic therapy in adult with severe sepsis or septic shock, admitted to the intensive care unit.

The study will be conducted in the intensive care unit (ICU) of the University Hospital Risoleta Tolentino Neves of the Federal University of Minas Gerais, Brazil. This is a 30-bed ICU with medical and surgical patients. All patients with suspected severe sepsis or septic shock admitted to the ICU will be assessed for eligibility. Patients developing severe sepsis or septic shock during their ICU stay will be also considered for enrollment.

Cultures of urine, blood, bronchoalveolar lavage ﬂuid, and tracheal aspirates will be performed on admission and during ICU stay as clinically indicated. Blood gases and imaging exams will also be performed as clinically indicated, similarly in both groups.

* Interventions:

All adult (\> 17 years old) patients with diagnosis of severe sepsis or septic shock will receive initial antibiotic therapy based on local guidelines and susceptibility patterns, according to the decision of the treating physician. They will have circulating PCT and CRP levels measured at baseline and daily until day 4 in both groups.

Eligible patients will be reassessed on day 4 and randomized at 1:1 basis to one of the two groups since any exclusion criteria (see below) is present at that time:

Group 1 - CRP group: the duration of antibiotic therapy will be based on circulating CRP levels.

Group 2 - PCT group: the duration of antibiotic therapy will be based on circulating PCT levels.

Patients enrolled in the study will undergo daily measurements of plasma CRP (Dry Chemistry - Johnsons \& Johnsons) and PCT (BRAHMS PCT VIDAS) levels up to stopping antibiotic therapy, every 48hr for two measurements in patients remaining in the ICU, and then, every 5 days.Patients will be followed up 28 days, or until death or hospital transference, which comes first. PCT and CRP results will be released in sealed envelopes. During the study period, only the results corresponding to the patient randomization group will be open; i.e., CRP for CRP group patients and PCT for PCT group patients.

- Criteria for antibiotic interruption:

The investigators will propose the interruption of antibiotics if:

1. The patients is clinically stable, without signs of active infection
2. CRP group: a relative reduction of 50% in baseline CRP levels, or a value lower than 25mg/dl is reached.
3. PCT group: a relative reduction of 90% in baseline PCT levels, or if a absolute value lower than 0.1 ng/ml is reached.

The final decision regarding antibiotic therapy will be always let to the discretion of the treating physician.

Eligibility criteria: Inclusion Criteria:

* age \> 17 years
* patients in intensive care unit
* signed informed consent
* suspected or confirmed severe sepsis or septic shock

Exclusion Criteria:

* Infections caused by Listeria spp, Legionella pneumophilia, Mycobacterium tuberculosis
* Bacteremia due S. aureus
* Infections requiring prolonged therapies, such as endocarditis, cerebral abscess, chronic osteomyelitis
* Suspected or confirmed infection caused by virus, parasites
* Infections caused by P. aeruginosa ou A. baumannii
* Severe immunosuppression (ex: AIDS, post bone-marrow transplant,cystic fibrosis)
* Traumatism latest five days
* Surgery latest 5 days
* Carcinoid tumor, lung cancer, medullary thyroid cancer

Primary outcomes:
measure: Duration of antibiotic therapy for the first episode of infection
timeFrame: 28 days
measure: Total antibiotic exposure days per 1,000 days
timeFrame: 28 days
measure: Days alive without antibiotics
timeFrame: 28 days
Secondary outcomes:
measure: All cause 28-day mortality
timeFrame: 28 days
measure: clinical cure rate
timeFrame: 28 days
measure: Infection relapse (diagnosed less than 48h after antibiotic discontinuation)
timeFrame: 48 hours
measure: Length of ICU stay
timeFrame: Whole hospitalization
measure: Nosocomial infection rate
timeFrame: 28 days
measure: In-hospital mortality
timeFrame: 28 days
measure: sepsis-associated death
timeFrame: 28 days
measure: Nosocomial superinfection (diagnosed more than 48hous after discontinuation of the antibiotic therapy given to the first episode of infection)
timeFrame: 28 days
measure: Isolation of resistant bacteria
timeFrame: 28 days
measure: Length of hospital stay
timeFrame: The whole hospitalization
Other outcomes:
Locations:
city: Belo Horizonte
country: Brazil
facility: Hospital das Clínicas - Universidade Federal de Minas Gerais
state: Minas Gerais
Study officials:
affiliation: Medical School of the Federal University of Minas Gerais
name: Vandack A Nobre, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Idem
name: Carolina F Oliveira, MD
role: STUDY_CHAIR
affiliation: Idem
name: Fernando A Botoni, PhD
role: STUDY_CHAIR
References:
citation: Oliveira CF, Botoni FA, Oliveira CR, Silva CB, Pereira HA, Serufo JC, Nobre V. Procalcitonin versus C-reactive protein for guiding antibiotic therapy in sepsis: a randomized trial. Crit Care Med. 2013 Oct;41(10):2336-43. doi: 10.1097/CCM.0b013e31828e969f.