(1,3)-β-D-glucan Based Diagnosis of Invasive Candida Infection in Sepsis (CandiSep)

(1,3)-β-D-glucan Based Diagnosis of Invasive Candida Infection Versus Culture Based Diagnosis in Patients With Severe Sepsis or Septic Shock

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.

Study Overview

• Status: Completed
• Conditions: Septic Shock; Severe Sepsis
• Intervention / Treatment: Other: Standard of care; Other: (1,3)-β-D-glucan guided therapy

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.

• Study Type: Interventional
• Enrollment (Actual): 342
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Augsburg, Germany, 86156
    • Hospital Augsburg
  • Bad Saarow, Germany
    • Helios Klinikum Bad Saarow
  • Bonn, Germany
    • University Hospital Bonn
  • Emden, Germany, 26721
    • Hospital Emden
  • Erlangen, Germany
    • University Hospital Erlangen
  • Frankfurt, Germany, 60590
    • University Hospital Frankfurt
  • Gottingen, Germany, 37099
    • University Hospital Göttingen
  • Greifswald, Germany, 17475
    • University Hospital Greifswald
  • Halle, Germany
    • University Hospital Halle
  • Hamburg, Germany, 20246
    • University Hospital Hamburg-Eppendorf
  • Heidelberg, Germany, 69120
    • University Hospital Heidelberg
  • Jena, Germany, 07740
    • Jena University Hospital
  • Kiel, Germany, 24105
    • University Hospital Schleswig-Holstein
  • Leipzig, Germany, 04103
    • University Hospital Leipzig
  • Münster, Germany
    • University Hospital Münster
  • Oldenburg, Germany, 26133
    • Hospital Oldenburg
  • Siegen, Germany
    • Diakonie Klinikum
  • Würzburg, Germany
    • University Hospital Würzburg

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:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control; Diagnosis of invasive candida infection according to standard of care.	Other: Standard of care; Patients are treated according to the ESCMID guidelines. Antifungal therapy is started if fungi are detected in the blood culture or other primary sterile body fluids.
Experimental: (1,3)-β-D-glucan guidance; Treatment according to BDG-result	Other: Standard of care; Patients are treated according to the ESCMID guidelines. Antifungal therapy is started if fungi are detected in the blood culture or other primary sterile body fluids.; Other: (1,3)-β-D-glucan guided therapy; Serum for (1,3)-β-D-glucan measurement is obtained after enrollment and 24 hours later. Antifungal therapy is started if at least one sample is 80 pg/ml or higher. If concomitantly taken microbiological cultures remain negative, antifungal therapy is continued only, if both (1,3)-β-D-glucan were at least 80 pg/ml. Blood cultures or other samples from primary sterile body fluids positive for fungi are treated with antifungals irrespective the (1,3)-β-D-glucan results.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
28 day mortality	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events		14 days
28 day antifungal-free survival		28 days
Candida Colonization	Candida colonization assessed by Candida Colonization Index	14 days
Time to antifungal therapy		14 days
Duration of organ support		14 days
Mean total SOFA score	Measure of organ dysfunction	14 days
ICU and hospital length of stay		Hospital length of stay
ICU and hospital mortality		Hospital length of stay
Diagnostic performance of (1,3)-β-D-glucan in comparison to PCR and other experimental diagnostics		2 days
Pharmacoeconomics		14 days

Collaborators and Investigators

• Sponsor: Center for Sepsis Control and Care, Germany
• Collaborators: Center for Clinical Studies, University Hospital Jena, Germany; Dept. of Microbiology, University Hospital Erlangen, Germany; Institute of Medical Statistics, Computer Sciences and Documentation, University Hospital Jena, Germany; Federal Ministry of Education and Research, Berlin, Germany; Associates of Cape Cod, Inc., East Falmouth, MA, USA
• Investigators: Principal Investigator: Frank Bloos, MD, Ph.D., Jena University Hospital

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 12, 2016
• Primary Completion (Actual): August 22, 2019
• Study Completion (Actual): September 17, 2019

Study Registration Dates

• First Submitted: April 6, 2016
• First Submitted That Met QC Criteria: April 6, 2016
• First Posted (Estimate): April 12, 2016

Study Record Updates

• Last Update Posted (Actual): August 19, 2022
• Last Update Submitted That Met QC Criteria: August 17, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Biomarker; Sepsis; Critically ill; Intensive care medicine; Invasive Candida Infection; (1,3)-β-D-glucan; Antifungal therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Systemic Inflammatory Response Syndrome; Inflammation; Bacterial Infections and Mycoses; Shock; Mycoses; Sepsis; Toxemia; Infections; Shock, Septic; Candidiasis
• Other Study ID Numbers: ZKSJ0087; 01EO1502 (Other Grant/Funding Number: Federal Ministry of Education and Research of Germany); U1111-1181-8724 (Registry Identifier: Universal Trial Number); DRKS00010285 (Registry Identifier: German Clinical Trial Register)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No