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

Primary Purpose

Severe Sepsis, Septic Shock

Status
Completed
Phase
Not Applicable
Locations
Germany
Study Type
Interventional
Intervention
Standard of care
(1,3)-β-D-glucan guided therapy
Sponsored by
Center for Sepsis Control and Care, Germany
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Severe Sepsis focused on measuring Sepsis, Invasive Candida Infection, Biomarker, (1,3)-β-D-glucan, Antifungal therapy, Intensive care medicine, Critically ill

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hospital Augsburg
  • HELIOS Klinikum Bad Saarow
  • University Hospital Bonn
  • Hospital Emden
  • University Hospital Erlangen
  • University Hospital Frankfurt
  • University Hospital Göttingen
  • University Hospital Greifswald
  • University Hospital Halle
  • University Hospital Hamburg-Eppendorf
  • University Hospital Heidelberg
  • Jena University Hospital
  • University Hospital Schleswig-Holstein
  • University Hospital Leipzig
  • University Hospital Münster
  • Hospital Oldenburg
  • Diakonie Klinikum
  • University Hospital Würzburg

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Control

(1,3)-β-D-glucan guidance

Arm Description

Diagnosis of invasive candida infection according to standard of care.

Treatment according to BDG-result

Outcomes

Primary Outcome Measures

28 day mortality

Secondary Outcome Measures

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

Full Information

First Posted
April 6, 2016
Last Updated
August 17, 2022
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
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1. Study Identification

Unique Protocol Identification Number
NCT02734550
Brief Title
(1,3)-β-D-glucan Based Diagnosis of Invasive Candida Infection in Sepsis
Acronym
CandiSep
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

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
September 12, 2016 (Actual)
Primary Completion Date
August 22, 2019 (Actual)
Study Completion Date
September 17, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the 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

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Severe Sepsis, Septic Shock
Keywords
Sepsis, Invasive Candida Infection, Biomarker, (1,3)-β-D-glucan, Antifungal therapy, Intensive care medicine, Critically ill

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
investigator-initiated prospective, multicenter, randomized, open, and parallel group study
Masking
None (Open Label)
Allocation
Randomized
Enrollment
342 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Control
Arm Type
Active Comparator
Arm Description
Diagnosis of invasive candida infection according to standard of care.
Arm Title
(1,3)-β-D-glucan guidance
Arm Type
Experimental
Arm Description
Treatment according to BDG-result
Intervention Type
Other
Intervention Name(s)
Standard of care
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
(1,3)-β-D-glucan guided therapy
Intervention Description
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.
Primary Outcome Measure Information:
Title
28 day mortality
Time Frame
28 days
Secondary Outcome Measure Information:
Title
28 day antifungal-free survival
Time Frame
28 days
Title
Candida Colonization
Description
Candida colonization assessed by Candida Colonization Index
Time Frame
14 days
Title
Time to antifungal therapy
Time Frame
14 days
Title
Duration of organ support
Time Frame
14 days
Title
Mean total SOFA score
Description
Measure of organ dysfunction
Time Frame
14 days
Title
ICU and hospital length of stay
Time Frame
Hospital length of stay
Title
ICU and hospital mortality
Time Frame
Hospital length of stay
Title
Adverse events
Time Frame
14 days
Title
Diagnostic performance of (1,3)-β-D-glucan in comparison to PCR and other experimental diagnostics
Time Frame
2 days
Title
Pharmacoeconomics
Time Frame
14 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Frank Bloos, MD, Ph.D.
Organizational Affiliation
Jena University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital Augsburg
City
Augsburg
ZIP/Postal Code
86156
Country
Germany
Facility Name
HELIOS Klinikum Bad Saarow
City
Bad Saarow
Country
Germany
Facility Name
University Hospital Bonn
City
Bonn
Country
Germany
Facility Name
Hospital Emden
City
Emden
ZIP/Postal Code
26721
Country
Germany
Facility Name
University Hospital Erlangen
City
Erlangen
Country
Germany
Facility Name
University Hospital Frankfurt
City
Frankfurt
ZIP/Postal Code
60590
Country
Germany
Facility Name
University Hospital Göttingen
City
Gottingen
ZIP/Postal Code
37099
Country
Germany
Facility Name
University Hospital Greifswald
City
Greifswald
ZIP/Postal Code
17475
Country
Germany
Facility Name
University Hospital Halle
City
Halle
Country
Germany
Facility Name
University Hospital Hamburg-Eppendorf
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
University Hospital Heidelberg
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Jena University Hospital
City
Jena
ZIP/Postal Code
07740
Country
Germany
Facility Name
University Hospital Schleswig-Holstein
City
Kiel
ZIP/Postal Code
24105
Country
Germany
Facility Name
University Hospital Leipzig
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Facility Name
University Hospital Münster
City
Münster
Country
Germany
Facility Name
Hospital Oldenburg
City
Oldenburg
ZIP/Postal Code
26133
Country
Germany
Facility Name
Diakonie Klinikum
City
Siegen
Country
Germany
Facility Name
University Hospital Würzburg
City
Würzburg
Country
Germany

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
30180873
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.
Results Reference
background
PubMed Identifier
35708758
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.
Results Reference
result

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

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