Negative Beta Glucan in ICU Patients

A Pilot Study for the Use of Biomarkers and Early Treatment of Invasive Candidiasis in ICU Patients

This is a prospective study aimed at testing a strategy of early initiation of an antifungal agent to patients admitted to intensive care units (ICUs) at risk for invasive candidiasis. Score system have been developed to identify groups at very high risk for the development of candidemia/invasive candidiasis in the ICU. These scoring system have used clinical information with or without data on Candida colonization, and have shown reasonable correlation with candidemia/invasive candidiasis. More recently, a biomarker - detection of 1,3-beta-D-glucan in the serum - has been tested in the early diagnosis of candidiasis. The incorporation of biomarkers such as beta-D-glucan could help clinicians to select a group at higher risk for candidemia, and despite the fact that these tests may give false-positive results, their negative predictive value could be of great help.

Therefore, the objectives of this study are:

1. To assess the frequency of positive biomarkers in ICU patients at high risk to develop invasive candidiasis/candidemia;
2. To test the strategy of early discontinuation of antifungal therapy based on repeatedly negative blood cultures and 1,3 beta-D-glucan in the serum.

Study Overview

• Status: Completed
• Conditions: Candidemia
• Intervention / Treatment: Drug: Anidulafungin

Detailed Description

Entry criteria are: In the ICU for >2 days AND systemic antibiotics >2 days OR central venous catheter for >days AND at least two of the following: total parenteral nutrition, dialysis, surgery, pancreatitis, receipt of corticosteroids, receipt of other immunosuppressive agents. In addition, patients must have a clinical sign of infection (either one of the following): fever, hypothermia, hypotension, unexplained acidosis, or unexplained elevation in C-reactive protein.

Eligible patients will be enrolled after signing an informed consent and will have blood obtained for culture and determination of 1,3 beta-D-glucan serum levels for 3 days, and will start anidulafungin IV.

If all tests are negative, anidulafungin will be discontinued on day 4. If 1,3 beta-D-glucan is positive (>80 pg/ml) and / or blood cultures are positive for Candida species, anidulafungin will be continued for >14 days.

• Study Type: Interventional
• Enrollment (Actual): 85
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • RJ
    • Rio de Janeiro, RJ, Brazil, 21941913
      • Federal University of Rio de Janeiro

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:

• In the ICU for >2 days AND

  • Systemic antibiotics on days 1-3 of ICU OR
  • Central venous catheter on days 1-3 of ICU

• AND at least 2 of:

  • Total parenteral nutrition on days 1-3 of ICU
  • Any dialysis on days 1-3 of ICU
  • Major surgery in the 7 days before admission in the ICU
  • Pancreatitis in the 7 days before admission in the ICU
  • Use of corticosteroids for at least 3 days in the 7 days before admission
  • Use of other immunosuppressive agents in the 7 days before admission in the ICU

• In addition, the patient must have at least one of the following:

  • Fever (axillary temperature >37.5 oC)
  • Hypothermia (axillary temperature <35 oC)
  • Hypotension
  • Unexplained acidosis
  • Unexplained elevation in C-reactive protein

Exclusion Criteria:

• Antifungal for >3 days
• Allergy to an echinocandin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Anidulafungin; Patients at risk will receive therapy with anidulafungin	Drug: Anidulafungin; Anidulafungin at a dose of 200 mg in the first day and 100 mg daily afterwards

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the Ocurrence of Candidemia in Patients With Negative 1,3 Beta-D-glucan Who Discontinue Anidulafungin	The main interest is to evaluate the ocurrence of candidemia in patients with negative 1,3 beta-D-glucan who discontinue anidulafungin	30 days

Collaborators and Investigators

• Sponsor: Universidade Federal do Rio de Janeiro
• Investigators: Study Chair: Marcio Nucci, MD, Universidade Federal do Rio de Janeiro

Publications and helpful links

General Publications

• Nucci M, Nouer SA, Esteves P, Guimaraes T, Breda G, de Miranda BG, Queiroz-Telles F, Colombo AL. Discontinuation of empirical antifungal therapy in ICU patients using 1,3-beta-d-glucan. J Antimicrob Chemother. 2016 Sep;71(9):2628-33. doi: 10.1093/jac/dkw188. Epub 2016 Jun 10.

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (ACTUAL): December 1, 2013
• Study Completion (ACTUAL): December 1, 2013

Study Registration Dates

• First Submitted: November 20, 2012
• First Submitted That Met QC Criteria: November 26, 2012
• First Posted (ESTIMATE): November 27, 2012

Study Record Updates

• Last Update Posted (ACTUAL): July 8, 2019
• Last Update Submitted That Met QC Criteria: April 18, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: intensive care unit; candidemia; 1,3 beta-D-glucan
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Bacterial Infections and Mycoses; Sepsis; Mycoses; Invasive Fungal Infections; Fungemia; Candidiasis; Candidiasis, Invasive; Candidemia; Anti-Infective Agents; Antifungal Agents; Anidulafungin
• Other Study ID Numbers: Early Therapy