Severe SepsisCandiSepNCT02734550
(1,3)-β-D-glucan Based Diagnosis of Invasive Candida Infection in Sepsis
A study testing (1,3)-β-D-glucan guided therapy in people with Severe Sepsis and Septic Shock, run by Center for Sepsis Control and Care, Germany at 18 sites in Germany.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Severe Sepsis, Septic Shock
- What is being tested?
- (1,3)-β-D-glucan guided therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 342 participants
- Where
- 18 sitesGermany
- Study dates
- 12 Sep 2016to 17 Sep 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- 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.
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
18 sites in 1 country.
18 sites in 1 country
Germany18 sites
Hospital Augsburg
Augsburg, 86156
HELIOS Klinikum Bad Saarow
Bad Saarow
University Hospital Bonn
Bonn
Hospital Emden
Emden, 26721
University Hospital Erlangen
Erlangen
University Hospital Frankfurt
Frankfurt, 60590
University Hospital Göttingen
Göttingen, 37099
University Hospital Greifswald
Greifswald, 17475
University Hospital Halle
Halle
University Hospital Hamburg-Eppendorf
Hamburg, 20246
University Hospital Heidelberg
Heidelberg, 69120
Jena University Hospital
Jena, 07740
University Hospital Schleswig-Holstein
Kiel, 24105
University Hospital Leipzig
Leipzig, 04103
University Hospital Münster
Münster
Hospital Oldenburg
Oldenburg, 26133
Diakonie Klinikum
Siegen
University Hospital Würzburg
Würzburg
About this study
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
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.
Read the 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
- Being tested
- Standard of care, (1,3)-β-D-glucan guided therapy
- Keywords
- Sepsis, Invasive Candida Infection, Biomarker, (1,3)-β-D-glucan, Antifungal therapy, Intensive care medicine, Critically ill
- Medical subject headings
- Sepsis, Shock, Septic, Critical Illness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard of careOther
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 therapyOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Control | Active comparator | Diagnosis of invasive candida infection according to standard of care. Receives: Other: Standard of care |
| (1,3)-β-D-glucan guidance | Experimental | Treatment according to BDG-result Receives: Other: Standard of care; Other: (1,3)-β-D-glucan guided therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
28 day mortality
Measured: 28 days
Secondary outcomes (10)
28 day antifungal-free survival
Measured: 28 days
Candida Colonization
Candida colonization assessed by Candida Colonization Index
Measured: 14 days
Time to antifungal therapy
Measured: 14 days
Duration of organ support
Measured: 14 days
Mean total SOFA score
Measure of organ dysfunction
Measured: 14 days
ICU and hospital length of stay
Measured: Hospital length of stay
ICU and hospital mortality
Measured: Hospital length of stay
Adverse events
Measured: 14 days
Diagnostic performance of (1,3)-β-D-glucan in comparison to PCR and other experimental diagnostics
Measured: 2 days
Pharmacoeconomics
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2016 (estimated)
- Study start12 Sep 2016
- Primary completion22 Aug 2019
- Study completion17 Sep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Severe SepsisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- investigator-initiated prospective, multicenter, randomized, open, and parallel group study
- Masking
- None (open label)
- Enrolment
- 342 participants (actual)
Sponsor and investigators
- Lead sponsor
- Center for Sepsis Control and Care, Germany
- Sponsor type
- University, hospital or other
- Collaborators
- Jena University Hospital, University Hospital Erlangen, Federal Ministry of Education and Research, Berlin, Germany, Associates of Cape Cod, Inc., East Falmouth, MA, USA
- Responsible party
- Sponsor
- Investigators
- Frank Bloos, MD, Ph.D., Principal investigator, Jena University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02734550
- Sponsor's protocol ID
- ZKSJ0087
- Other IDs
- 01EO1502, U1111-1181-8724, DRKS00010285
- Acronym
- CandiSep
- Status last verified
- Aug 2022
- First submitted
- 6 Apr 2016
- Last updated
- 19 Aug 2022
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 30180873Bloos 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.
PubMed 35708758
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02734550
- Acronym / sponsor ID
- CandiSep / ZKSJ0087
- Conditions
- Severe Sepsis, Septic Shock
- Keywords
- Sepsis, Invasive Candida Infection, Biomarker, (1,3)-β-D-glucan, Antifungal therapy, Intensive care medicine, Critically ill
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 342 participants (actual)
- Lead sponsor
- Center for Sepsis Control and Care, GermanyUniversity, hospital or other
- Collaborators
- Jena University Hospital, University Hospital Erlangen, Federal Ministry of Education and Research, Berlin, Germany, Associates of Cape Cod, Inc., East Falmouth, MA, USA
- Study start
- 12 Sep 2016 (actual)
- Primary completion
- 22 Aug 2019 (actual)
- Study completion
- 17 Sep 2019 (actual)
- First posted
- 12 Apr 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- investigator-initiated prospective, multicenter, randomized, open, and parallel group study
| Arm | Type | Receives |
|---|---|---|
| Control | Active comparator | Other: Standard of careDiagnosis of invasive candida infection according to standard of care. |
| (1,3)-β-D-glucan guidance | Experimental | Other: Standard of care, Other: (1,3)-β-D-glucan guided therapyTreatment according to BDG-result |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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:
- 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.
Key exclusion criteria (11 listed)
- Pregnant or lactating women
- Ongoing invasive candida infection
- systemic antifungal therapy
- liver cirrhosis Child C
- cardiopulmonary bypass within the last 4 weeks
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Standard of carePatients 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 guidance, Control |
| (1,3)-β-D-glucan guided therapySerum 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. | Other | (1,3)-β-D-glucan guidance |
Primary outcome
28 day mortality
Time frame: 28 days
10 secondary outcomes
28 day antifungal-free survival
Time frame: 28 days
Candida Colonization
Time frame: 14 days
Time to antifungal therapy
Time frame: 14 days
Duration of organ support
Time frame: 14 days
Mean total SOFA score
Time frame: 14 days
ICU and hospital length of stay
Time frame: Hospital length of stay
ICU and hospital mortality
Time frame: Hospital length of stay
Adverse events
Time frame: 14 days
Diagnostic performance of (1,3)-β-D-glucan in comparison to PCR and other experimental diagnostics
Time frame: 2 days
Pharmacoeconomics
Time frame: 14 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2022.
- Background: PubMed 30180873Bloos 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 publication: PubMed 35708758Bloos 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Frank Bloos, MD, Ph.D. principal investigator
Jena University Hospital
18 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing (1,3)-β-D-glucan guided therapy in people with Severe Sepsis and Septic Shock, run by Center for Sepsis Control and Care, Germany at 18 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
28 day mortality (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02734550, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2022.