Trial Outcomes & Findings for β-D-Glucan (BDG) Surveillance With Preemptive Anidulafungin vs. Standard Care for Invasive Candidiasis in Surgical Intensive Care Unit (SICU) Patients (NCT NCT00672841)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

64 participants

Primary outcome timeframe

Participants were followed until ICU discharge, an average of 17 days

Results posted on

2015-02-06

Participant Flow

Patients were recruited from June 2008 to December 2010 on three intensive care units.

Participant milestones

Participant milestones
Measure	Standard Care, Empiric Treatment Standard care group. Empiric antifungal therapy initiated by physician preference for the treatment of suspected invasive candidiasis.	Active Surveillance, Preemptive Therapy 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
Overall Study STARTED	17	47
Overall Study COMPLETED	16	32
Overall Study NOT COMPLETED	1	15

Reasons for withdrawal

Reasons for withdrawal
Measure	Standard Care, Empiric Treatment Standard care group. Empiric antifungal therapy initiated by physician preference for the treatment of suspected invasive candidiasis.	Active Surveillance, Preemptive Therapy 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
Overall Study Comfort care	1	4
Overall Study icteric specimens	0	3
Overall Study Antifungal therapy, negative glucan	0	4
Overall Study Adverse Event	0	3
Overall Study Pregnancy	0	1

Baseline Characteristics

β-D-Glucan (BDG) Surveillance With Preemptive Anidulafungin vs. Standard Care for Invasive Candidiasis in Surgical Intensive Care Unit (SICU) Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Standard Care, Empiric Treatment n=17 Participants Standard care group. Empiric antifungal therapy initiated by physician preference for the treatment of suspected invasive candidiasis.	Active Surveillance, Preemptive Therapy n=47 Participants 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	Total n=64 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	11 Participants n=5 Participants	30 Participants n=7 Participants	41 Participants n=5 Participants
Age, Categorical >=65 years	6 Participants n=5 Participants	17 Participants n=7 Participants	23 Participants n=5 Participants
Age, Continuous	53 years STANDARD_DEVIATION 19 • n=5 Participants	53 years STANDARD_DEVIATION 20 • n=7 Participants	53 years STANDARD_DEVIATION 19 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	16 Participants n=7 Participants	20 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	31 Participants n=7 Participants	44 Participants n=5 Participants
Region of Enrollment United States	17 participants n=5 Participants	47 participants n=7 Participants	64 participants n=5 Participants

PRIMARY outcome

Timeframe: Participants were followed until ICU discharge, an average of 17 days

Population: Two study subjects in the preemptive therapy arm were excluded from the analysis of assay sensitivity and specific due to icteric serum specimens.

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.

Outcome measures

Outcome measures
Measure	Active Surveillance, Preemptive Therapy n=45 Participants 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	Standard Care, Empiric Treatment n=17 Participants Standard care group. Empiric antifungal therapy initiated by physician preference for the treatment of suspected invasive candidiasis.
Clinical Utility of Biweekly β-D-glucan (BDG) Testing in At-risk Intensive Care Unit (ICU) Patients. True BDG Positives	3 participants	3 participants
Clinical Utility of Biweekly β-D-glucan (BDG) Testing in At-risk Intensive Care Unit (ICU) Patients. True BDG Negative	19 participants	9 participants
Clinical Utility of Biweekly β-D-glucan (BDG) Testing in At-risk Intensive Care Unit (ICU) Patients. False BDG Positives	23 participants	5 participants
Clinical Utility of Biweekly β-D-glucan (BDG) Testing in At-risk Intensive Care Unit (ICU) Patients. False BGD Negatives	0 participants	0 participants

PRIMARY outcome

Timeframe: weekly until ICU discharge

Population: Subjects receiving at least 1 dose of anidulafungin were assessed.

reported as the Number of Adverse Events Possibly Related to Study Drug

Outcome measures

Outcome measures
Measure	Active Surveillance, Preemptive Therapy n=17 Participants 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	Standard Care, Empiric Treatment n=45 Participants Standard care group. Empiric antifungal therapy initiated by physician preference for the treatment of suspected invasive candidiasis.
Safety and Tolerability of Preemptive Anidulafungin	0 events	10 events

SECONDARY outcome

Timeframe: Study Completion, an average of 17 days

Population: Data was not collected for this outcome measure.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Participants were followed until ICU discharge, an average of 17 days

Population: 4 subjects in the preemptive therapy were excluded from this analysis. These subjects were treated with empiric antifungal therapy despite repeatedly negative glucan results.

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.

Outcome measures

Outcome measures
Measure	Active Surveillance, Preemptive Therapy n=17 Participants 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	Standard Care, Empiric Treatment n=41 Participants Standard care group. Empiric antifungal therapy initiated by physician preference for the treatment of suspected invasive candidiasis.
Incidence of Proven or Probable Invasive Fungal Infection (IFI)	3 participants	3 participants

Adverse Events

Standard Care, Empiric Treatment

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Active Surveillance, Preemptive Therapy

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Standard Care, Empiric Treatment n=17 participants at risk Standard care group. Empiric antifungal therapy initiated by physician preference for the treatment of suspected invasive candidiasis.	Active Surveillance, Preemptive Therapy n=47 participants at risk 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
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/5	9.5% 2/21 • Number of events 2
Hepatobiliary disorders Abnormal liver function tests	0.00% 0/5	42.9% 9/21 • Number of events 9
Metabolism and nutrition disorders Hypocalcemia	0.00% 0/5	9.5% 2/21 • Number of events 2

Additional Information

Kimberly E. Hanson, MD, MHS

University of Utah

Phone: 801.585.2867

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place