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

Sponsor

Center for Sepsis Control and Care, Germany (Other)

Overall Status

Completed

CT.gov ID

NCT02734550

Collaborator

Center for Clinical Studies, University Hospital Jena, Germany (Other), Dept. of Microbiology, University Hospital Erlangen, Germany (Other), Institute of Medical Statistics, Computer Sciences and Documentation, University Hospital Jena, Germany (Other), Federal Ministry of Education and Research, Berlin, Germany (Other), Associates of Cape Cod, Inc., East Falmouth, MA, USA (Other)

342

Enrollment

Locations

Arms

36.1

Actual Duration (Months)

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Severe Sepsis Septic Shock	Other: Standard of care Other: (1,3)-β-D-glucan guided therapy	N/A

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 Design

Study Type:

Interventional

Actual Enrollment :

342 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

investigator-initiated prospective, multicenter, randomized, open, and parallel group studyinvestigator-initiated prospective, multicenter, randomized, open, and parallel group study

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

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

Actual Study Start Date :

Sep 12, 2016

Actual Primary Completion Date :

Aug 22, 2019

Actual Study Completion Date :

Sep 17, 2019

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

28 day mortality [28 days]

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Hospital Augsburg	Augsburg	Germany	86156
2	HELIOS Klinikum Bad Saarow	Bad Saarow	Germany
3	University Hospital Bonn	Bonn	Germany
4	Hospital Emden	Emden	Germany	26721
5	University Hospital Erlangen	Erlangen	Germany
6	University Hospital Frankfurt	Frankfurt	Germany	60590
7	University Hospital Göttingen	Gottingen	Germany	37099
8	University Hospital Greifswald	Greifswald	Germany	17475
9	University Hospital Halle	Halle	Germany
10	University Hospital Hamburg-Eppendorf	Hamburg	Germany	20246
11	University Hospital Heidelberg	Heidelberg	Germany	69120
12	Jena University Hospital	Jena	Germany	07740
13	University Hospital Schleswig-Holstein	Kiel	Germany	24105
14	University Hospital Leipzig	Leipzig	Germany	04103
15	University Hospital Münster	Münster	Germany
16	Hospital Oldenburg	Oldenburg	Germany	26133
17	Diakonie Klinikum	Siegen	Germany
18	University Hospital Würzburg	Würzburg	Germany

Sponsors and Collaborators

Center for Sepsis Control and Care, Germany
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