Clinical trial NCT02734550: (1,3)-β-D-glucan Based Diagnosis of Invasive Candida Infection in Sepsis
Official title: (1,3)-β-D-glucan Based Diagnosis of Invasive Candida Infection Versus Culture Based Diagnosis in Patients With Severe Sepsis or Septic Shock
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Severe Sepsis
Septic Shock
Keywords: Sepsis
Invasive Candida Infection
Biomarker
(1,3)-β-D-glucan
Antifungal therapy
Intensive care medicine
Critically ill
Lead sponsor: Center for Sepsis Control and Care, Germany
Sponsor class: OTHER
Collaborators: name: Center for Clinical Studies, University Hospital Jena, Germany
name: Dept. of Microbiology, University Hospital Erlangen, Germany
name: Institute of Medical Statistics, Computer Sciences and Documentation, University Hospital Jena, Germany
name: Federal Ministry of Education and Research, Berlin, Germany
name: Associates of Cape Cod, Inc., East Falmouth, MA, USA
First posted: 2016-04-12
Enrollment: 342
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: investigator-initiated prospective, multicenter, randomized, open, and parallel group study
Primary purpose: DIAGNOSTIC

Brief summary: This prospective randomized multicenter study evaluates whether the decision to prescribe antifungals guided by (1,3)-β-D-glucan in comparison to standard of care shortens time to antifungal therapy and reduces mortality in patients with severe sepsis or septic shock and a high risk of invasive candida infection.

Detailed description: (1,3)-β-D-glucan is a component of the cell wall of many fungi including candida spp. and is present in the blood of patients with invasive candida infection (ICI). Several studies showed a good diagnostic accuracy (1,3)-β-D-glucan in predicting ICI. However, others have challenged (1,3)-β-D-glucan as a diagnostic tool in critically ill patients as many substances used in the intensive care unit might affect the results of the assay. The goal of this study is to investigate whether (1,3)-β-D-glucan can early identify sepsis patients in need of antifungal therapy. Patients randomized to the standard of care group receive antifungals depending on microbiological results according to current guidelines. Patients randomized to the BDG group receive antifungals depending on the (1,3)-β-D-glucan plasma concentration on day 1 and day after diagnosing sepsis. Therapy may be modified according to microbiological results.

Eligibility criteria: Inclusion Criteria:

* Severe sepsis or septic shock
* Onset of sepsis no longer than 24 hours
* Increased risk of invasive candida infection with at least one of the following criteria:

  * total parenteral nutrition ≥48 hours
  * abdominal surgery within the last 7 days
  * antimicrobial therapy for at least 48 hours within the last 7 days
  * Acute or chronic renal failure with renal replacement therapy
* Age ≥18 years
* Informed consent of the patient or legal representative or delayed consent process is started if patient is incapable of giving informed consent and no legal representative is available.

Exclusion Criteria:

* Pregnant or lactating women
* Ongoing invasive candida infection
* systemic antifungal therapy
* liver cirrhosis Child C
* cardiopulmonary bypass within the last 4 weeks
* treatment with immunoglobulins within the last 14 days
* immunosuppression (solid organ transplantation, AISA, leukopenia)
* participation in another intervention study
* no commitment to full therapy (i.e. DNR order)
* Infauste Prognose aufgrund von Nebenerkrankungen
* kin to or colleague of study personnel

Primary outcomes:
measure: 28 day mortality
timeFrame: 28 days
Secondary outcomes:
measure: 28 day antifungal-free survival
timeFrame: 28 days
measure: Candida Colonization
timeFrame: 14 days
measure: Time to antifungal therapy
timeFrame: 14 days
measure: Duration of organ support
timeFrame: 14 days
measure: Mean total SOFA score
timeFrame: 14 days
measure: ICU and hospital length of stay
timeFrame: Hospital length of stay
measure: ICU and hospital mortality
timeFrame: Hospital length of stay
measure: Adverse events
timeFrame: 14 days
measure: Diagnostic performance of (1,3)-β-D-glucan in comparison to PCR and other experimental diagnostics
timeFrame: 2 days
measure: Pharmacoeconomics
timeFrame: 14 days
Other outcomes:
Locations:
city: Augsburg
country: Germany
facility: Hospital Augsburg
city: Bad Saarow
country: Germany
facility: HELIOS Klinikum Bad Saarow
city: Bonn
country: Germany
facility: University Hospital Bonn
city: Emden
country: Germany
facility: Hospital Emden
city: Erlangen
country: Germany
facility: University Hospital Erlangen
city: Frankfurt
country: Germany
facility: University Hospital Frankfurt
city: Gottingen
country: Germany
facility: University Hospital Göttingen
city: Greifswald
country: Germany
facility: University Hospital Greifswald
city: Halle
country: Germany
facility: University Hospital Halle
city: Hamburg
country: Germany
facility: University Hospital Hamburg-Eppendorf
city: Heidelberg
country: Germany
facility: University Hospital Heidelberg
city: Jena
country: Germany
facility: Jena University Hospital
city: Kiel
country: Germany
facility: University Hospital Schleswig-Holstein
city: Leipzig
country: Germany
facility: University Hospital Leipzig
city: Münster
country: Germany
facility: University Hospital Münster
city: Oldenburg
country: Germany
facility: Hospital Oldenburg
city: Siegen
country: Germany
facility: Diakonie Klinikum
city: Würzburg
country: Germany
facility: University Hospital Würzburg
Study officials:
affiliation: Jena University Hospital
name: Frank Bloos, MD, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bloos F, Held J, Schlattmann P, Brillinger N, Kurzai O, Cornely OA, Thomas-Ruddel D. (1,3)-beta-D-glucan-based diagnosis of invasive Candida infection versus culture-based diagnosis in patients with sepsis and with an increased risk of invasive Candida infection (CandiSep): study protocol for a randomized controlled trial. Trials. 2018 Sep 4;19(1):472. doi: 10.1186/s13063-018-2868-0.
citation: Bloos F, Held J, Kluge S, Simon P, Kogelmann K, de Heer G, Kuhn SO, Jarczak D, Motsch J, Hempel G, Weiler N, Weyland A, Druner M, Grundling M, Meybohm P, Richter D, Jaschinski U, Moerer O, Gunther U, Schadler D, Weiss R, Putensen C, Castellanos I, Kurzai O, Schlattmann P, Cornely OA, Bauer M, Thomas-Ruddel D; SepNet Study Group. (1 --> 3)-beta-D-Glucan-guided antifungal therapy in adults with sepsis: the CandiSep randomized clinical trial. Intensive Care Med. 2022 Jul;48(7):865-875. doi: 10.1007/s00134-022-06733-x. Epub 2022 Jun 16.