Invasive Candidiasis
Conditions
Keywords
Candidiasis, Invasive Candidiasis, Fungal Infection, Empirical Therapy
Brief summary
This is a pilot feasibility study that investigates antifungal therapy with caspofungin in patients at high-risk for developing invasive candidiasis in a critical care setting.
Detailed description
Hypothesis: In high-risk non-neutropenic participants in the ICU, the proportion of participants discontinued from study therapy in order to be empirically treated with antifungal therapy for suspected candidiasis outside of the context of this protocol is less than 20% (i.e., the upper bound of the 95% confidence interval for the observed proportion is less than 20%).
Interventions
70 mg of caspofungin administered intravenously (IV) on Day 1 followed by 50 mg daily for at least 6 additional days (maximum duration study therapy is 14 days)
DRUGPlacebo
Placebo to caspofungin (normal saline) on Day 1 followed by placebo daily for at least 6 additional days (maximum duration study therapy is 14 days)
Sponsors
Mycoses Study Group
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Hospitalization for a minimum of 3 days in an ICU and expectation to stay in the ICU for at least another 48 hours * Meets the following high-risk criteria: Requires mechanical ventilation at the time of study entry; and has a central venous catheter in place at the time of study entry; and is receiving broad spectrum antibiotics at the time of study entry; AND meets at least one of the following criteria: Required parenteral nutrition during the current ICU admission; or required renal dialysis during the current ICU admission; or had major surgery during or within the 7 days before the current ICU admission; or was diagnosed with pancreatitis during or within the 7 days before the current ICU admission; or required systemic steroids or other immunosuppressive agents during or within the 7 days before the current ICU admission * Meets at least one of the following criteria of suspected infection at the time of study entry or within the 24 hours before study entry: Temperature ≥38° C or ≤36° C (oral equivalent); or hypotension (systolic blood pressure of \<90 mm Hg) or significant drop in blood pressure (40 mm Hg) from the participant's normal baseline; or elevated white blood cell count of ≥12,000/mm\^3 * Candida is growing in at least one non-sterile culture site collected during the current ICU admission * Female of childbearing potential has a negative serum or urine pregnancy test before enrollment
Exclusion criteria
* Females pregnant or breast feeding * History of allergy, hypersensitivity, or any serious reaction to caspofungin or another member of the echinocandin class (e.g., micafungin, anidulafungin) * Neutropenia or expected to develop neutropenia during study therapy * Diagnosis of acquired immune deficiency syndrome (AIDS), aplastic anemia, or chronic granulomatous disease * Diagnosis of moderate or severe hepatic insufficiency * Patient not expected to survive at least 24 hours * Received systemic (IV or oral) antifungal therapy within 10 days before study entry * Active diagnosis of proven or probable invasive fungal infection (IFI) * Currently on or has received an investigational agent within 10 days before study entry * Any condition or concomitant illness which might confuse the study results or pose additional risk in administering the study therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Proportion of Patients Discontinued From Study Therapy to be Treated With Empirical Antifungal Therapy Outside of the Context of the Study. | 1 to 14 days | The feasibility of conducting a major randomized study of caspofungin for empirical therapy for invasive candidiasis in high-risk non-neutropenic intensive care unit (ICU) participants was to be assessed by the incidence of study therapy discontinuations due to investigators choosing to treat participants with empirical antifungal therapy outside of the context of this protocol. Study drug was administered for a minimum of 7 days to a maximum of 14 days provided participants had no evidence of confirmed breakthrough invasive Candida infection while receiving study drug. |
Participant flow
Pre-assignment details
This study was terminated early due to low participant enrollment. One of the 15 participants randomized to treatment inappropriately received a systemic antifungal agent before starting study drug and was not included in the baseline characteristics, safety, or efficacy analyses.
Participants by arm
| Arm | Count |
|---|---|
| Caspofungin Caspofungin 70 mg caspofungin administered intravenously (IV) on Day 1 followed by 50 mg daily for at least 6 additional days (maximum duration study therapy is 14 days) | 6 |
| Placebo Placebo to caspofungin (normal saline) on Day 1 followed by placebo daily for at least 6 additional days (maximum duration study therapy is 14 days) | 8 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Changed to Open-Label Caspofungin | 1 | 0 |
| Overall Study | Changed to Other Antifungal Therapy | 1 | 2 |
| Overall Study | Invasive Fungal Infection at Baseline | 0 | 1 |
| Overall Study | Received Systemic Antifungal Prestudy | 0 | 1 |
Baseline characteristics
| Characteristic | Caspofungin | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 60.2 years STANDARD_DEVIATION 20.1 | 53.0 years STANDARD_DEVIATION 10.6 | 56.1 years STANDARD_DEVIATION 15.1 |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 6 | 6 / 8 |
| serious Total, serious adverse events | 3 / 6 | 3 / 8 |
Outcome results
Primary
The Proportion of Patients Discontinued From Study Therapy to be Treated With Empirical Antifungal Therapy Outside of the Context of the Study.
The feasibility of conducting a major randomized study of caspofungin for empirical therapy for invasive candidiasis in high-risk non-neutropenic intensive care unit (ICU) participants was to be assessed by the incidence of study therapy discontinuations due to investigators choosing to treat participants with empirical antifungal therapy outside of the context of this protocol. Study drug was administered for a minimum of 7 days to a maximum of 14 days provided participants had no evidence of confirmed breakthrough invasive Candida infection while receiving study drug.
Time frame: 1 to 14 days
Population: Of the 114 participants anticipated to enroll in this study, 15 actually enrolled and only 14 received study drug. The participant who did not receive study drug was discontinued; the remaining 14 received at least one dose of study drug, met inclusion/exclusion criteria, and therefore qualified for the full analysis set used for summary analyses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Caspofungin | The Proportion of Patients Discontinued From Study Therapy to be Treated With Empirical Antifungal Therapy Outside of the Context of the Study. | 1 Participants |
| Placebo | The Proportion of Patients Discontinued From Study Therapy to be Treated With Empirical Antifungal Therapy Outside of the Context of the Study. | 2 Participants |