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

NCT02734550 | Completed DMC

• 4 other identifiers: ZKSJ008701EO1502U1111-1181-8724DRKS00010285
• Study Type: interventional
• Target: 342
• Locations: 1 country
• Sites: 18

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.

Conditions

Severe Sepsis; Septic Shock

Keywords

Sepsis; Invasive Candida Infection; Biomarker; (1,3)-β-D-glucan; Antifungal therapy; Intensive care medicine; Critically ill

Outcome Measures

Primary Outcomes (1)

• 28 day mortality

  28 days

Secondary Outcomes (10)

• 28 day antifungal-free survival

  28 days

• Candida Colonization

  14 days

• Time to antifungal therapy

  14 days

• Duration of organ support

  14 days

• Mean total SOFA score

  14 days

Study Arms (2)

Control

ACTIVE COMPARATOR

Diagnosis of invasive candida infection according to standard of care.

Other: Standard of care

(1,3)-β-D-glucan guidance

EXPERIMENTAL

Treatment according to BDG-result

Other: Standard of care; Other: (1,3)-β-D-glucan guided therapy

Interventions

Standard of care 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; Control

(1,3)-β-D-glucan guided therapy 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.

(1,3)-β-D-glucan guidance

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Center for Sepsis Control and Care, Germany: lead
• Center for Clinical Studies, University Hospital Jena, Germany: collaborator
• Dept. of Microbiology, University Hospital Erlangen, Germany: collaborator
• Institute of Medical Statistics, Computer Sciences and Documentation, University Hospital Jena, Germany: collaborator
• Federal Ministry of Education and Research, Berlin, Germany: collaborator
• Associates of Cape Cod, Inc., East Falmouth, MA, USA: collaborator

Study Sites (18)

Hospital Augsburg

Augsburg, 86156, Germany

Location

HELIOS Klinikum Bad Saarow

Bad Saarow, Germany

Location

University Hospital Bonn

Bonn, Germany

Location

Hospital Emden

Emden, 26721, Germany

Location

University Hospital Erlangen

Erlangen, Germany

Location

University Hospital Frankfurt

Frankfurt, 60590, Germany

Location

University Hospital Göttingen

Göttingen, 37099, Germany

Location

University Hospital Greifswald

Greifswald, 17475, Germany

Location

University Hospital Halle

Halle, Germany

Location

University Hospital Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

University Hospital Heidelberg

Heidelberg, 69120, Germany

Location

Jena University Hospital

Jena, 07740, Germany

Location

University Hospital Schleswig-Holstein

Kiel, 24105, Germany

Location

University Hospital Leipzig

Leipzig, 04103, Germany

Location

University Hospital Münster

Münster, Germany

Location

Hospital Oldenburg

Oldenburg, 26133, Germany

Location

Diakonie Klinikum

Siegen, Germany

Location

University Hospital Würzburg

Würzburg, Germany

Location

Related Publications (2)

• 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.

  PMID: 30180873 BACKGROUND

• 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.

  PMID: 35708758 RESULT

MeSH Terms

Conditions

Sepsis; Shock, Septic; Critical Illness

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Disease Attributes

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Frank Bloos, MD, Ph.D.

  Jena University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: investigator-initiated prospective, multicenter, randomized, open, and parallel group study

Study Record Dates

• First Submitted: April 6, 2016
• First Posted: April 12, 2016
• Study Start: September 12, 2016
• Primary Completion: August 22, 2019
• Study Completion: September 17, 2019
• Last Updated: August 19, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

DE (18)