Use of Inflammatory Biomarkers to Guide Antibiotic Therapy in Patients With Severe Infections

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.

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.

Study Overview

• Status: Completed
• Conditions: Septic Shock; Severe Sepsis
• Intervention / Treatment: Other: C-reactive protein guided antibiotic therapy; Other: Procalcitonin guided antibiotic therapy

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.

• Study Type: Interventional
• Enrollment (Actual): 94
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil
      • Hospital das Clínicas - Universidade Federal de Minas Gerais

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:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Group 1 - C-reactive protein (CRP) guided ab therapy; Intervention on antibiotic therapy will be based on circulating CRP levels	Other: C-reactive protein guided antibiotic therapy; plasma CRP measurement to guide the duration of antibiotic therapy
ACTIVE_COMPARATOR: Group 2 - procalcitonin (PCT) guided ab therapy; Intervention on antibiotic therapy will be based on circulating PCT levels	Other: Procalcitonin guided antibiotic therapy; plasma PCT measurement to guide the duration of antibiotic therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Duration of antibiotic therapy for the first episode of infection	28 days
Total antibiotic exposure days per 1,000 days	28 days
Days alive without antibiotics	28 days

Secondary Outcome Measures

Outcome Measure	Time Frame
All cause 28-day mortality	28 days
Nosocomial infection rate	28 days
clinical cure rate	28 days
Infection relapse (diagnosed less than 48h after antibiotic discontinuation)	48 hours
Length of ICU stay	Whole hospitalization
In-hospital mortality	28 days
sepsis-associated death	28 days
Nosocomial superinfection (diagnosed more than 48hous after discontinuation of the antibiotic therapy given to the first episode of infection)	28 days
Isolation of resistant bacteria	28 days
Length of hospital stay	The whole hospitalization

Collaborators and Investigators

• Sponsor: Federal University of Minas Gerais
• Collaborators: Fundação de Amparo à Pesquisa do estado de Minas Gerais
• Investigators: Principal Investigator: Vandack A Nobre, PhD, Medical School of the Federal University of Minas Gerais; Study Chair: Carolina F Oliveira, MD, Idem; Study Chair: Fernando A Botoni, PhD, Idem

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (ACTUAL): May 1, 2012
• Study Completion (ACTUAL): May 1, 2012

Study Registration Dates

• First Submitted: July 7, 2009
• First Submitted That Met QC Criteria: July 7, 2009
• First Posted (ESTIMATE): July 8, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): February 3, 2016
• Last Update Submitted That Met QC Criteria: February 1, 2016
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: sepsis; procalcitonin; C-reactive protein; antibiotic therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Sepsis; Shock, Septic; Anti-Infective Agents; Antitubercular Agents; Anti-Bacterial Agents; Antibiotics, Antitubercular
• Other Study ID Numbers: PRO_Protocol01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Results published in the Critical Care Medicine, 2013