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

Septic Shock Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00934011
• Other study ID #: PRO_Protocol01
• Status: Completed
• Phase: N/A
• First received: July 7, 2009
• Last updated: February 1, 2016
• Start date: September 2009
• Est. completion date: May 2012

Study information

• Verified date: June 2012
• Source: Federal University of Minas Gerais
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 94
• Est. completion date: May 2012
• Est. primary completion date: May 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Sepsis
• Septic Shock
• Severe Sepsis
• Shock, Septic

Intervention

Other:
• C-reactive protein guided antibiotic therapy
plasma CRP measurement to guide the duration of antibiotic therapy
• Procalcitonin guided antibiotic therapy
plasma PCT measurement to guide the duration of antibiotic therapy

Locations

Country	Name	City	State
Brazil	Hospital das Clínicas - Universidade Federal de Minas Gerais	Belo Horizonte	Minas Gerais

Sponsors (2)

Lead Sponsor	Collaborator
Federal University of Minas Gerais	Fundação de Amparo à Pesquisa do estado de Minas Gerais

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Duration of antibiotic therapy for the first episode of infection		28 days	No
Primary	Total antibiotic exposure days per 1,000 days		28 days	No
Primary	Days alive without antibiotics		28 days	No
Secondary	All cause 28-day mortality		28 days	Yes
Secondary	clinical cure rate		28 days	Yes
Secondary	Infection relapse (diagnosed less than 48h after antibiotic discontinuation)		48 hours	Yes
Secondary	Length of ICU stay		Whole hospitalization	No
Secondary	Nosocomial infection rate		28 days	Yes
Secondary	In-hospital mortality		28 days	Yes
Secondary	sepsis-associated death		28 days	Yes
Secondary	Nosocomial superinfection (diagnosed more than 48hous after discontinuation of the antibiotic therapy given to the first episode of infection)		28 days	Yes
Secondary	Isolation of resistant bacteria		28 days	Yes
Secondary	Length of hospital stay		The whole hospitalization	No