Clinical trial NCT01734525: Negative Beta Glucan in ICU Patients
Official title: A Pilot Study for the Use of Biomarkers and Early Treatment of Invasive Candidiasis in ICU Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Candidemia
Keywords: candidemia
intensive care unit
1,3 beta-D-glucan
Lead sponsor: Universidade Federal do Rio de Janeiro
Sponsor class: OTHER
First posted: 2012-11-27
Enrollment: 85
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Evaluate the Ocurrence of Candidemia in Patients With Negative 1,3 Beta-D-glucan Who Discontinue Anidulafungin
timeFrame: 30 days
Secondary outcomes:
Other outcomes:
Locations:
city: Rio de Janeiro
country: Brazil
facility: Federal University of Rio de Janeiro
state: RJ
Study officials:
affiliation: Universidade Federal do Rio de Janeiro
name: Marcio Nucci, MD
role: STUDY_CHAIR
References:
citation: 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.