Invasive Candidiasis
Conditions
Keywords
Candida, Candidemia, Systemic Candidiasis, ICU, Intensive Care Unit, Critical Care Unit, Anidulafungin, Ecalta, Eraxis, Fluconazole, Voriconazole
Brief summary
To evaluate the efficacy and safety of anidulafungin in the treatment of systemic fungal infections in intensive care and critical care unit patients.
Interventions
DRUGAnidulafungin
Anidulafungin Intravenous Administration
DRUGFluconazole
Oral Administration of Fluconazole
DRUGVoriconazole
Oral Administration of Voriconazole
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
ICU patients with a diagnosis of documented candidemia or invasive candidiasis and belonging to one or more of the following specific populations: * Post-abdominal surgery. * Elderly \> 65 years old. * Renal insufficiency / failure / hemodialysis. * Solid tumor. * Solid-organ (liver, kidney, lung, heart) transplant recipients. * Hepatic insufficiency. * Neutropenic including hematology oncology patients.
Exclusion criteria
Patients with poor venous access that would preclude IV drug delivery or multiple blood draws.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Global Treatment Response Success at End of Treatment | End of Treatment (Day 14 to Day 56) | Global response based on combination of clinical and microbiological outcomes; success defined as clinical response of cure (resolution of signs and symptoms of Candida infection) or improvement (significant, but incomplete resolution of signs and symptoms of Candida infection) in conjunction with microbiological eradication (follow-up culture negative for Candida species) or presumed eradication (follow-up culture not available and clinical response of success). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Global Response Success at 2 Weeks After End of Treatment | 2 weeks after End of Treatment (Day 14 + 14 up to Day 56 + 14) | Global response based on combination of clinical and microbiological outcomes; success defined as clinical response of cure (resolution of signs and symptoms of Candida infection) or improvement (significant, but incomplete resolution of signs and symptoms of Candida infection) in conjunction with microbiological eradication (follow-up culture negative for Candida species) or presumed eradication (follow-up culture not available and clinical response of success). |
| Percentage of Participants With Global Response Success 6 Weeks After End of Treatment | 6 weeks after End of Treatment (Day 14 + 42 up to Day 56 + 42) | Global response based on combination of clinical and microbiological outcomes; success defined as clinical response of cure (resolution of signs and symptoms of Candida infection) or improvement (significant, but incomplete resolution of signs and symptoms of Candida infection) in conjunction with microbiological eradication (follow-up culture negative for Candida species) or presumed eradication (follow-up culture not available and clinical response of success). |
| Percentage of Participants With Global Response Success at End of Intravenous Treatment (EOIVT) | EOIVT (Day 10 up to Day 42) | Global response based on combination of clinical and microbiological outcomes; success defined as clinical response of cure (resolution of signs and symptoms of Candida infection) or improvement (significant, but incomplete resolution of signs and symptoms of Candida infection) in conjunction with microbiological eradication (follow-up culture negative for Candida species) or presumed eradication (follow-up culture not available and clinical response of success). |
| Day 90 Survival | Day 90 | Percentage of participants known or assumed to be alive on Day 90. |
| Time to Successful Intensive Care Unit (ICU) Discharge | Day 1 up to Day 56 | Time from start of study medication to successful ICU discharge (by end of treatment \[EOT\]), defined as being alive on the day after the EOT visit, not being in the ICU on the day after the EOT visit, and being classed as a global treatment success at EOT. |
| Time to First Negative Blood Culture | Day 1 up to Day 42 | Negative blood culture defined as first negative culture that was not followed by a positive culture within the next 3 days (or 4 days if negative culture was observed on or after Day 10) from start of study medication until end of intravenous treatment (EOIVT). Time to first negative culture includes the first day of study medication. |
Countries
Austria, Belgium, Canada, Czechia, Denmark, France, Germany, Greece, Hungary, Italy, Netherlands, Poland, Portugal, Romania, Russia, Slovakia, Turkey (Türkiye), Ukraine, United Kingdom
Participant flow
Recruitment details
Adult specific participants were recruited from intensive care unit (ICU) populations.
Pre-assignment details
Two-hundred twenty one (221) participants were screened; 5 participants were screen failures who did not receive study medication.
Participants by arm
| Arm | Count |
|---|---|
| Anidulafungin Anidulafungin: 200 milligrams (mg) Day 1, 100 mg once daily from Day 2 (minimum of 9 days, maximum of 41 days). After Day 10 option to treat with oral azole therapy (voriconazole or fluconazole) at a dose determined by local clinical practice up to a maximum of 56 days from Day 1. | 216 |
| Total | 216 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 13 |
| Overall Study | Death | 65 |
| Overall Study | Did not Meet Entrance Criteria | 27 |
| Overall Study | Insufficient Clinical Response | 1 |
| Overall Study | Lack of Efficacy | 6 |
| Overall Study | Lost to Follow-up | 5 |
| Overall Study | Other | 8 |
| Overall Study | Protocol Violation | 15 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Anidulafungin |
|---|---|
| Age, Customized 18 to 44 years | 27 participants |
| Age, Customized <18 years | 0 participants |
| Age, Customized 45 to 64 years | 89 participants |
| Age, Customized ≥ 65 years | 100 participants |
| Sex: Female, Male Female | 85 Participants |
| Sex: Female, Male Male | 131 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 78 / 216 |
| serious Total, serious adverse events | 107 / 216 |
Outcome results
Primary
Percentage of Participants With Global Treatment Response Success at End of Treatment
Global response based on combination of clinical and microbiological outcomes; success defined as clinical response of cure (resolution of signs and symptoms of Candida infection) or improvement (significant, but incomplete resolution of signs and symptoms of Candida infection) in conjunction with microbiological eradication (follow-up culture negative for Candida species) or presumed eradication (follow-up culture not available and clinical response of success).
Time frame: End of Treatment (Day 14 to Day 56)
Population: Modified Intent-To-Treat (MITT) analysis set: all participants in the ITT population with confirmed diagnosis of candidemia or invasive candidiasis, documented within 96 hours prior to initiation of study treatment or 48 hours after commencing treatment. N excludes participants with missing or unknown global responses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anidulafungin | Percentage of Participants With Global Treatment Response Success at End of Treatment | 69.5 percentage of participants |
Secondary
Day 90 Survival
Percentage of participants known or assumed to be alive on Day 90.
Time frame: Day 90
Population: MITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anidulafungin | Day 90 Survival | 54.1 percentage of participants |
Comparison: Kaplan-Meier estimate of survival at Day 90 (survivor function).95% CI: [45.9, 60.9]Kaplan-Meier
Secondary
Percentage of Participants With Global Response Success 6 Weeks After End of Treatment
Global response based on combination of clinical and microbiological outcomes; success defined as clinical response of cure (resolution of signs and symptoms of Candida infection) or improvement (significant, but incomplete resolution of signs and symptoms of Candida infection) in conjunction with microbiological eradication (follow-up culture negative for Candida species) or presumed eradication (follow-up culture not available and clinical response of success).
Time frame: 6 weeks after End of Treatment (Day 14 + 42 up to Day 56 + 42)
Population: MITT; N excludes participants with missing or unknown global responses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anidulafungin | Percentage of Participants With Global Response Success 6 Weeks After End of Treatment | 50.5 percentage of participants |
Secondary
Percentage of Participants With Global Response Success at 2 Weeks After End of Treatment
Global response based on combination of clinical and microbiological outcomes; success defined as clinical response of cure (resolution of signs and symptoms of Candida infection) or improvement (significant, but incomplete resolution of signs and symptoms of Candida infection) in conjunction with microbiological eradication (follow-up culture negative for Candida species) or presumed eradication (follow-up culture not available and clinical response of success).
Time frame: 2 weeks after End of Treatment (Day 14 + 14 up to Day 56 + 14)
Population: MITT; N excludes participants with missing or unknown global responses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anidulafungin | Percentage of Participants With Global Response Success at 2 Weeks After End of Treatment | 60.2 percentage of participants |
Secondary
Percentage of Participants With Global Response Success at End of Intravenous Treatment (EOIVT)
Global response based on combination of clinical and microbiological outcomes; success defined as clinical response of cure (resolution of signs and symptoms of Candida infection) or improvement (significant, but incomplete resolution of signs and symptoms of Candida infection) in conjunction with microbiological eradication (follow-up culture negative for Candida species) or presumed eradication (follow-up culture not available and clinical response of success).
Time frame: EOIVT (Day 10 up to Day 42)
Population: MITT; N excludes participants with missing or unknown global responses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anidulafungin | Percentage of Participants With Global Response Success at End of Intravenous Treatment (EOIVT) | 70.7 percentage of participants |
Secondary
Time to First Negative Blood Culture
Negative blood culture defined as first negative culture that was not followed by a positive culture within the next 3 days (or 4 days if negative culture was observed on or after Day 10) from start of study medication until end of intravenous treatment (EOIVT). Time to first negative culture includes the first day of study medication.
Time frame: Day 1 up to Day 42
Population: MITT. N = participants who received a minimum of 3 days of dosing with anidulafungin, excluding participants who experienced invasive candidiasis either at baseline or while on anidulafungin and participants who did not have a first negative blood culture by EOIVT.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Anidulafungin | Time to First Negative Blood Culture | 3.7 days |
Secondary
Time to Successful Intensive Care Unit (ICU) Discharge
Time from start of study medication to successful ICU discharge (by end of treatment \[EOT\]), defined as being alive on the day after the EOT visit, not being in the ICU on the day after the EOT visit, and being classed as a global treatment success at EOT.
Time frame: Day 1 up to Day 56
Population: MITT. N = participants who had a successful ICU discharge.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Anidulafungin | Time to Successful Intensive Care Unit (ICU) Discharge | 16.2 days |