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

NCT ID: NCT02734550

Last Updated: 2022-08-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 342 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-12
• Study Completion Date: 2019-09-17

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.

Conditions

Severe Sepsis; Septic Shock

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Control

Diagnosis of invasive candida infection according to standard of care.

Group Type: ACTIVE_COMPARATOR

Standard of care

Intervention Type: OTHER

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.

(1,3)-β-D-glucan guidance

Treatment according to BDG-result

Group Type: EXPERIMENTAL

Standard of care

Intervention Type: OTHER

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.

(1,3)-β-D-glucan guided therapy

Intervention Type: OTHER

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: OTHER

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Center for Clinical Studies, University Hospital Jena, Germany

UNKNOWN

Sponsor Role: collaborator

Dept. of Microbiology, University Hospital Erlangen, Germany

UNKNOWN

Sponsor Role: collaborator

Institute of Medical Statistics, Computer Sciences and Documentation, University Hospital Jena, Germany

UNKNOWN

Sponsor Role: collaborator

Federal Ministry of Education and Research, Berlin, Germany

UNKNOWN

Sponsor Role: collaborator

Associates of Cape Cod, Inc., East Falmouth, MA, USA

UNKNOWN

Sponsor Role: collaborator

Center for Sepsis Control and Care, Germany

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Frank Bloos, MD, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Jena University Hospital

Locations

Hospital Augsburg

Augsburg, , Germany

HELIOS Klinikum Bad Saarow

Bad Saarow, , Germany

University Hospital Bonn

Bonn, , Germany

Hospital Emden

Emden, , Germany

University Hospital Erlangen

Erlangen, , Germany

University Hospital Frankfurt

Frankfurt, , Germany

University Hospital Göttingen

Göttingen, , Germany

University Hospital Greifswald

Greifswald, , Germany

University Hospital Halle

Halle, , Germany

University Hospital Hamburg-Eppendorf

Hamburg, , Germany

University Hospital Heidelberg

Heidelberg, , Germany

Jena University Hospital

Jena, , Germany

University Hospital Schleswig-Holstein

Kiel, , Germany

University Hospital Leipzig

Leipzig, , Germany

University Hospital Münster

Münster, , Germany

Hospital Oldenburg

Oldenburg, , Germany

Diakonie Klinikum

Siegen, , Germany

University Hospital Würzburg

Würzburg, , Germany

Countries

Germany

References

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.

Reference Type: BACKGROUND

PMID: 30180873 (View on PubMed)

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.

Reference Type: RESULT

PMID: 35708758 (View on PubMed)

Other Identifiers

01EO1502

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

U1111-1181-8724

Identifier Type: REGISTRY

Identifier Source: secondary_id

DRKS00010285

Identifier Type: REGISTRY

Identifier Source: secondary_id

ZKSJ0087

Identifier Type: -

Identifier Source: org_study_id