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A B-D-Glucan Driven Antifungal Stewardship Approach for Invasive Candidiasis

Primary Purpose

Invasive Candidiases, Abdominal Infection

Status
Unknown status
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
De-escalation
Sponsored by
University of Bologna
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Invasive Candidiases focused on measuring beta-d-glucan, abdominal candidiasis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • a. adult (≥ 18 year) patients; b. signed informed consent before surgical procedure; c. severe sepsis or septic shock; d. at least one of the following conditions: i) post-operative peritonitis, ii) recurrent gastrointestinal perforation, iii) post-operative hepatobiliary and/or pancreatic disorders including necrotizing pancreatitis, iv) post-operative intra-abdominal abscess, and v) anastomotic leak.

Exclusion Criteria:

  • a. diagnosis of candidiasis before the enrollment b. exposure in the past 30 days to any antifungal treatment or diagnosis of invasive fungal infection; c. pregnancy or lactation; d. history of allergy to any of the antifungal drugs; e. major immunosuppression conditions including: i. neutropenia (<0.5 × 109 neutrophils/L [<500 neutrophils/mm3] for >10 days), ii. receipt of an allogeneic stem cell transplant or solid organ transplantation, iii. inherited severe immunodeficiency (such as chronic granulomatous disease or severe combined immunodeficiency), iv. HIV infection with lymphocyte T CD4+ cell count < 200/mmc. f. patients with poor prognosis or unable to sign informed consent.

Sites / Locations

  • Azienda Ospealiero Universitaria di Bologna Policlinico S.Orsola-MalpighiRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

De-escalation

Standard of care

Arm Description

In this group, investigators will manage the antifungal therapy according to the BG levels as follows: antifungal therapy will be stopped immediately after the BG response in case of serum BG <80 pg/ml in presence of clinical stability (CS); antifungal therapy will be continued until further BG determination, both for BG levels between 80-200 pg/ml and for BG <80 pg/ml in patients without CS. In these cases, if the following BG value is <80 pg/ml antifungal therapy will be stopped independently from the CS achievement. antifungal therapy will be continued until day 10 for BG levels >200 pg/ml

In this group antifungal treatment will be continued until clinician's decision. Investigators will be blinded to the BG levels of patients enrolled in this arm, The BG results will be faxed directly to the coordinating center.

Outcomes

Primary Outcome Measures

Antifungal consumption
Days of antifungal consumption will be compared between the two groups
Mortality
28-day mortality will be compared between the two groups
Length of stay
Length of stay in ICU will be compared between the two groups

Secondary Outcome Measures

Accuracy of BG
sensitivity, specificity, positive predictive value, negative predictive value of BG in the diagnosis of invasive candidiasis

Full Information

First Posted
March 18, 2017
Last Updated
April 17, 2019
Sponsor
University of Bologna
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1. Study Identification

Unique Protocol Identification Number
NCT03090334
Brief Title
A B-D-Glucan Driven Antifungal Stewardship Approach for Invasive Candidiasis
Official Title
A B-D-Glucan Driven Antifungal Stewardship Approach to Manage Empirical Therapy in Patients at Very High Risk for Invasive Candidiasis: a Randomized Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
April 2019
Overall Recruitment Status
Unknown status
Study Start Date
March 1, 2017 (Actual)
Primary Completion Date
June 2020 (Anticipated)
Study Completion Date
December 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Bologna

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a multicenter, prospective, open-label, randomized trial. Patients with severe abdominal condition developing severe sepsis or septic shock and receiving broad spectrum antibiotic and antifungal treatment will be randomized (1:1) to: discontinue antifungal treatment based on negative (<80 pg/ml) result of 1,3 beta-d-glucan performed on day 0,3,6 and 10 continue antifungal treatment according with attending physician's decision.
Detailed Description
Primary objective: Our objective is to establish whether a strategy based on beta-d-glucan (BG) assessment could achieve reduced antifungal consumption in patients with severe abdominal condition developing severe sepsis and septic shock without any impact on the outcome Secondary objectives i) Assess the accuracy of BG in the diagnosis of invasive candidiasis (IC) in in critically ill patients with a severe abdominal condition who develop severe sepsis or septic shock. ii) Describe the changes over the time of BG value according with colonization status, infection or none the aforementioned events. Material and Methods Study design: a multicenter, open label, randomized trial Population: all the patients with a severe abdominal condition who develop a severe sepsis or septic shock. Inclusion Criteria: adult (≥ 18 year) patients; signed informed consent before surgical procedure; severe sepsis or septic shock; at least one of the following conditions: i) post-operative peritonitis, ii) recurrent gastrointestinal perforation, iii) post-operative hepatobiliary and/or pancreatic disorders including necrotizing pancreatitis, iv) post-operative intra-abdominal abscess, and v) anastomotic leak. Exclusion criteria a. diagnosis of candidiasis before the enrollment b. exposure in the past 30 days to any antifungal treatment or diagnosis of invasive fungal infection; c. pregnancy or lactation; d. history of allergy to any of the antifungal drugs; e. major immunosuppression conditions including: i. neutropenia (<0.5 × 109 neutrophils/L [<500 neutrophils/mm3] for >10 days), ii. receipt of an allogeneic stem cell transplant or solid organ transplantation, iii. inherited severe immunodeficiency (such as chronic granulomatous disease or severe combined immunodeficiency), iv. HIV infection with lymphocyte T CD4+ cell count < 200/mmc. f. patients with poor prognosis or unable to sign informed consent. Procedures Pre-randomization procedures At the time of patient enrollment (within 24 h from onset of severe sepsis/septic shock), a standardized diagnostic work-up must be performed including at least: i) two sets of blood cultures; ii) 5 surveillance cultures (rectal swab, urine culture, pharyngeal swab, axillary swab, groin swab). iii) in case of re-intervention or percutaneous drainage: Gram stain and culture of intra-abdominal samples; iv) serum BG determination. Antibiotic and antifungal empirical therapy should be started immediately after collection of microbiological samples according with a predefined standard of care (see appendix 1). Once completed this procedures patients will proceed to randomization. Randomization Patient eligible for the study after the beginning of antifungal therapy will be randomized 1:1 to receive (Group A) a BG driven de-escalation strategy or (Group B) a course of antifungal treatment based on the care provider's decision. In both groups, if cultures yield invasive candidiasis (see below) the patient will be managed in according with guidelines and excluded from the per-protocol analysis. In both groups, BG determination will be repeated at day +3, +6 and +10 after starting antifungal therapy. Randomization will be carried out providing closed envelopes to the participating centers immediately before the study onset.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Invasive Candidiases, Abdominal Infection
Keywords
beta-d-glucan, abdominal candidiasis

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Care Provider
Masking Description
Care provider will be blinded to result of BG in patients enrolled in the standard of care arm
Allocation
Randomized
Enrollment
180 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
De-escalation
Arm Type
Experimental
Arm Description
In this group, investigators will manage the antifungal therapy according to the BG levels as follows: antifungal therapy will be stopped immediately after the BG response in case of serum BG <80 pg/ml in presence of clinical stability (CS); antifungal therapy will be continued until further BG determination, both for BG levels between 80-200 pg/ml and for BG <80 pg/ml in patients without CS. In these cases, if the following BG value is <80 pg/ml antifungal therapy will be stopped independently from the CS achievement. antifungal therapy will be continued until day 10 for BG levels >200 pg/ml
Arm Title
Standard of care
Arm Type
No Intervention
Arm Description
In this group antifungal treatment will be continued until clinician's decision. Investigators will be blinded to the BG levels of patients enrolled in this arm, The BG results will be faxed directly to the coordinating center.
Intervention Type
Diagnostic Test
Intervention Name(s)
De-escalation
Intervention Description
Antifungal therapy will be stopped according with BG results
Primary Outcome Measure Information:
Title
Antifungal consumption
Description
Days of antifungal consumption will be compared between the two groups
Time Frame
28 days
Title
Mortality
Description
28-day mortality will be compared between the two groups
Time Frame
28 days
Title
Length of stay
Description
Length of stay in ICU will be compared between the two groups
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Accuracy of BG
Description
sensitivity, specificity, positive predictive value, negative predictive value of BG in the diagnosis of invasive candidiasis
Time Frame
28 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: a. adult (≥ 18 year) patients; b. signed informed consent before surgical procedure; c. severe sepsis or septic shock; d. at least one of the following conditions: i) post-operative peritonitis, ii) recurrent gastrointestinal perforation, iii) post-operative hepatobiliary and/or pancreatic disorders including necrotizing pancreatitis, iv) post-operative intra-abdominal abscess, and v) anastomotic leak. Exclusion Criteria: a. diagnosis of candidiasis before the enrollment b. exposure in the past 30 days to any antifungal treatment or diagnosis of invasive fungal infection; c. pregnancy or lactation; d. history of allergy to any of the antifungal drugs; e. major immunosuppression conditions including: i. neutropenia (<0.5 × 109 neutrophils/L [<500 neutrophils/mm3] for >10 days), ii. receipt of an allogeneic stem cell transplant or solid organ transplantation, iii. inherited severe immunodeficiency (such as chronic granulomatous disease or severe combined immunodeficiency), iv. HIV infection with lymphocyte T CD4+ cell count < 200/mmc. f. patients with poor prognosis or unable to sign informed consent.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Maddalena Giannella, MD, phD
Phone
+39 0512143199
Email
maddalena.giannella@unibo.it
First Name & Middle Initial & Last Name or Official Title & Degree
Michele Bartoletti, MD
Phone
+39 0512143199
Email
michele.bartoletti4@unibo.it
Facility Information:
Facility Name
Azienda Ospealiero Universitaria di Bologna Policlinico S.Orsola-Malpighi
City
Bologna
ZIP/Postal Code
40138
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maddalena Giannella, MD, PhD
Phone
+39 051 2143199
Email
maddalena.giannella@unibo.it

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
24105327
Citation
Bassetti M, Marchetti M, Chakrabarti A, Colizza S, Garnacho-Montero J, Kett DH, Munoz P, Cristini F, Andoniadou A, Viale P, Rocca GD, Roilides E, Sganga G, Walsh TJ, Tascini C, Tumbarello M, Menichetti F, Righi E, Eckmann C, Viscoli C, Shorr AF, Leroy O, Petrikos G, De Rosa FG. A research agenda on the management of intra-abdominal candidiasis: results from a consensus of multinational experts. Intensive Care Med. 2013 Dec;39(12):2092-106. doi: 10.1007/s00134-013-3109-3. Epub 2013 Oct 9.
Results Reference
background
PubMed Identifier
22423135
Citation
Kollef M, Micek S, Hampton N, Doherty JA, Kumar A. Septic shock attributed to Candida infection: importance of empiric therapy and source control. Clin Infect Dis. 2012 Jun;54(12):1739-46. doi: 10.1093/cid/cis305. Epub 2012 Mar 15.
Results Reference
background
PubMed Identifier
25091787
Citation
Maubon D, Garnaud C, Calandra T, Sanglard D, Cornet M. Resistance of Candida spp. to antifungal drugs in the ICU: where are we now? Intensive Care Med. 2014 Sep;40(9):1241-55. doi: 10.1007/s00134-014-3404-7. Epub 2014 Aug 5.
Results Reference
background
PubMed Identifier
23315320
Citation
Clancy CJ, Nguyen MH. Finding the "missing 50%" of invasive candidiasis: how nonculture diagnostics will improve understanding of disease spectrum and transform patient care. Clin Infect Dis. 2013 May;56(9):1284-92. doi: 10.1093/cid/cit006. Epub 2013 Jan 11.
Results Reference
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A B-D-Glucan Driven Antifungal Stewardship Approach for Invasive Candidiasis

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