Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| GA88517X |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Pfizer | INDUSTRY |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This is a single center, prospective, open label assessment of β-D-glucan surveillance with preemptive anidulafungin therapy versus standard care for the prevention of invasive candidiasis in at-risk surgical intensive care unit (SICU) patients. Subjects will be stratified by APACHE II score and randomized in 3:1 fashion to either biweekly surveillance using the β-D-glucan assay or standard care. Subjects in the active monitoring arm will receive intravenous anidulafungin should the β-D-glucan exceed 60 pg/mL on a single determination. Subjects in the standard care arm will have biweekly blood draws for β-D-glucan, but the specimens will be batched and tested retrospectively. Antifungal use in the standard care arm is at the discretion of the treating physicians. The primary study end-points are the feasibility of a preemptive antifungal strategy in a SICU setting, β-D-glucan test characteristics, and the safety and tolerability of preemptive anidulafungin. Risks associated with study participation include the risks associated with blood draws, study drug related side effects, and the potential for loss of confidentiality.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 2 | Active Comparator | Standard care/empiric therapy group |
|
| 1 | Experimental | Active surveillance/ preemptive therapy group |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Preemptive Therapy with Anidulafungin | Drug | Subjects in the active surveillance arm who develop a single positive β-D-glucan test will receive preemptive anidulafungin intravenously. Preemptive therapy will include a loading dose of 200mg followed by 100mg maintenance therapy once a day. The loading and maintenance doses are derived from the FDA cleared schedule for Invasive Candidiasis and candidemia. Preemptive therapy will continue for 14 days. |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical Utility of Biweekly β-D-glucan (BDG) Testing in At-risk Intensive Care Unit (ICU) Patients. | Clinical utility was defined as β-D-glucan test performance. Biweekly βDG testing used a threshold of ≥ 60 pg/ml to indicate a positive test for invasive candidiasis. True and false positives, and true and false negatives were confirmed using a composite clinical definition of invasive candidiasis that combines physical symptom/signs and microbiology. Cases of proven/probable invasive fungal infection (IFI) were adjudicated by a single reviewer blinded to group assignment and BDG results. | Participants were followed until ICU discharge, an average of 17 days |
| Safety and Tolerability of Preemptive Anidulafungin | reported as the Number of Adverse Events Possibly Related to Study Drug | weekly until ICU discharge |
| Measure | Description | Time Frame |
|---|---|---|
| Validate Gene Expression Signatures Predictive of IC | Study Completion, an average of 17 days | |
| Incidence of Proven or Probable Invasive Fungal Infection (IFI) | Institution specific criteria were used to establish a diagnosis of proven or probable invasive candidiasis. Other IFIs were classified according to the European Organization for Research and Treatment of Cancer/Mycosis Study Group (EORTC/MSG) criteria. However, BDG results were not factored into the EORTC/MSG criteria. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Kimberly E Hanson, MD | Utah | Principal Investigator |
| Barbara D Alexander, MD | Duke | Principal Investigator |
| John Perfect, MD | Duke | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Duke University Medical Center | Durham | North Carolina | 27710 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22879929 | Derived | Hanson KE, Pfeiffer CD, Lease ED, Balch AH, Zaas AK, Perfect JR, Alexander BD. beta-D-glucan surveillance with preemptive anidulafungin for invasive candidiasis in intensive care unit patients: a randomized pilot study. PLoS One. 2012;7(8):e42282. doi: 10.1371/journal.pone.0042282. Epub 2012 Aug 6. |
Not provided
Not provided
Not provided
Patients were recruited from June 2008 to December 2010 on three intensive care units.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Standard Care, Empiric Treatment | Standard care group. Empiric antifungal therapy initiated by physician preference for the treatment of suspected invasive candidiasis. |
| FG001 | Active Surveillance, Preemptive Therapy |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
| Empiric antifungal therapy based on physician discretion. | Drug | Patients in the standard care group may receive antifungal prophylaxis and/or treatment at any time based on the discretion of the treating physician. |
|
| Participants were followed until ICU discharge, an average of 17 days |
Active surveillance group. Preemptive therapy (i.e., intravenous anidulafungin 200mg on day one, then 100mg daily x 14 days) initiated in response to a positive 1,3-beta-D glucan test for the presumptive early treatment of invasive candidiasis
| COMPLETED |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Standard Care, Empiric Treatment | Standard care group. Empiric antifungal therapy initiated by physician preference for the treatment of suspected invasive candidiasis. |
| BG001 | Active Surveillance, Preemptive Therapy | Active surveillance group. Preemptive therapy initiated in response to a positive 1,3-beta-D glucan test for the presumptive early treatment of invasive candidiasis |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Clinical Utility of Biweekly β-D-glucan (BDG) Testing in At-risk Intensive Care Unit (ICU) Patients. | Clinical utility was defined as β-D-glucan test performance. Biweekly βDG testing used a threshold of ≥ 60 pg/ml to indicate a positive test for invasive candidiasis. True and false positives, and true and false negatives were confirmed using a composite clinical definition of invasive candidiasis that combines physical symptom/signs and microbiology. Cases of proven/probable invasive fungal infection (IFI) were adjudicated by a single reviewer blinded to group assignment and BDG results. | Two study subjects in the preemptive therapy arm were excluded from the analysis of assay sensitivity and specific due to icteric serum specimens. | Posted | Number | participants | Participants were followed until ICU discharge, an average of 17 days |
|
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Validate Gene Expression Signatures Predictive of IC | Data was not collected for this outcome measure. | Posted | Study Completion, an average of 17 days |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Incidence of Proven or Probable Invasive Fungal Infection (IFI) | Institution specific criteria were used to establish a diagnosis of proven or probable invasive candidiasis. Other IFIs were classified according to the European Organization for Research and Treatment of Cancer/Mycosis Study Group (EORTC/MSG) criteria. However, BDG results were not factored into the EORTC/MSG criteria. | 4 subjects in the preemptive therapy were excluded from this analysis. These subjects were treated with empiric antifungal therapy despite repeatedly negative glucan results. | Posted | Number | participants | Participants were followed until ICU discharge, an average of 17 days |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | Safety and Tolerability of Preemptive Anidulafungin | reported as the Number of Adverse Events Possibly Related to Study Drug | Subjects receiving at least 1 dose of anidulafungin were assessed. | Posted | Number | events | weekly until ICU discharge |
|
|
Not provided
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Standard Care, Empiric Treatment | Standard care group. Empiric antifungal therapy initiated by physician preference for the treatment of suspected invasive candidiasis. | 0 | 17 | 0 | 17 | ||
| EG001 | Active Surveillance, Preemptive Therapy | Active surveillance group. Preemptive therapy initiated in response to a positive 1,3-beta-D glucan test for the presumptive early treatment of invasive candidiasis | 0 | 47 | 10 | 47 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thrombocytopenia | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Abnormal liver function tests | Hepatobiliary disorders | Systematic Assessment |
| ||
| Hypocalcemia | Metabolism and nutrition disorders | Systematic Assessment |
|
This study represents a 1st attempt at preemptive antifungal therapy based on the fungal biomarker 1,3-Beta-D-Glucan in the intensive care unit. Main limitation: the small number of subjects with proven/probable invasive candidiasis.
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kimberly E. Hanson, MD, MHS | University of Utah | 801.585.2867 | kim.hanson@hsc.utah.edu |
| ID | Term |
|---|---|
| D058365 | Candidiasis, Invasive |
| D058387 | Candidemia |
| ID | Term |
|---|---|
| D002177 | Candidiasis |
| D009181 | Mycoses |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| D000072742 | Invasive Fungal Infections |
| D016469 | Fungemia |
| D018805 | Sepsis |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| D000077612 | Anidulafungin |
| ID | Term |
|---|---|
| D054714 | Echinocandins |
| D010456 | Peptides, Cyclic |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
Not provided
Not provided
| >=65 years |
|
| Male |
|
| False BDG Positives |
|
| False BGD Negatives |
|
Clinical specificity of the BDG test was calculated for the study groups combined
| % Specificity |
| Specificity |
| 50 |
| 95 |
Specificity [0.50]= True negatives [n=28]/ True negatives + False positives [56]) |
| No |
| Superiority or Other |
|
|
|
|