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

• ClinicalTrials.gov Identifier: NCT00934011
• Recruitment Status: Completed
• First Posted: July 8, 2009
• Last Update Posted: February 3, 2016
• Sponsor: Federal University of Minas Gerais
• Collaborator: Fundação de Amparo à Pesquisa do estado de Minas Gerais
• Information provided by (Responsible Party): Vandack Alencar Nobre, Federal University of Minas Gerais

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Severe Sepsis; Septic Shock	Other: C-reactive protein guided antibiotic therapy; Other: Procalcitonin guided antibiotic therapy	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 94 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• 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 Start Date: September 2009
• Actual Primary Completion Date: May 2012
• Actual Study Completion Date: May 2012

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Duration of antibiotic therapy for the first episode of infection [ Time Frame: 28 days ]
2. Total antibiotic exposure days per 1,000 days [ Time Frame: 28 days ]
3. Days alive without antibiotics [ Time Frame: 28 days ]

Secondary Outcome Measures :

1. All cause 28-day mortality [ Time Frame: 28 days ]
2. clinical cure rate [ Time Frame: 28 days ]
3. Infection relapse (diagnosed less than 48h after antibiotic discontinuation) [ Time Frame: 48 hours ]
4. Length of ICU stay [ Time Frame: Whole hospitalization ]
5. Nosocomial infection rate [ Time Frame: 28 days ]
6. In-hospital mortality [ Time Frame: 28 days ]
7. sepsis-associated death [ Time Frame: 28 days ]
8. Nosocomial superinfection (diagnosed more than 48hous after discontinuation of the antibiotic therapy given to the first episode of infection) [ Time Frame: 28 days ]
9. Isolation of resistant bacteria [ Time Frame: 28 days ]
10. Length of hospital stay [ Time Frame: The whole hospitalization ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Brazil

Hospital das Clínicas - Universidade Federal de Minas Gerais

Belo Horizonte, Minas Gerais, Brazil

Sponsors and Collaborators

Federal University of Minas Gerais

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Vandack Alencar Nobre, Associate Professor, PhD, Federal University of Minas Gerais
• ClinicalTrials.gov Identifier: NCT00934011
• Other Study ID Numbers: PRO_Protocol01
• First Posted: July 8, 2009
• Last Update Posted: February 3, 2016
• Last Verified: June 2012

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Results published in the Critical Care Medicine, 2013

Keywords provided by Vandack Alencar Nobre, Federal University of Minas Gerais:

C-reactive protein; procalcitonin; sepsis; antibiotic therapy

Additional relevant MeSH terms:

Sepsis; Shock, Septic; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Shock; Anti-Bacterial Agents; Antibiotics, Antitubercular; Anti-Infective Agents; Antitubercular Agents