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

Septic Shock Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02734550
• Other study ID #: ZKSJ0087
• Secondary ID: 01EO1502U1111-11
• Status: Completed
• Phase: N/A
• Start date: September 12, 2016
• Est. completion date: September 17, 2019

Study information

• Verified date: August 2022
• Source: Center for Sepsis Control and Care, Germany
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 342
• Est. completion date: September 17, 2019
• Est. primary completion date: August 22, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Candidiasis
• Infections
• Sepsis
• Septic Shock
• Severe Sepsis
• Shock, Septic
• Toxemia

Intervention

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.
• (1,3)-ß-D-glucan guided therapy
Serum for (1,3)-ß-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)-ß-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)-ß-D-glucan results.

Locations

Country	Name	City	State
Germany	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	Gottingen
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

Sponsors (6)

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

Country where clinical trial is conducted

Germany, 

References & Publications (2)

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, Drüner M, Gründling M, Meybohm P, Richter D, Jaschinski U, Moerer O, Günther U, Schädler D, Weiss R, Putensen C, Castellanos I, Kurzai — View Citation

Bloos F, Held J, Schlattmann P, Brillinger N, Kurzai O, Cornely OA, Thomas-Rüddel D. (1,3)-ß-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. — View Citation

Outcome

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