Central Nervous System Fungal Infections, Fungemia, Lung Diseases, Fungal, Mycoses
Conditions
Brief summary
The purpose of this study is to compare the efficacy of anidulafungin versus fluconazole for the prevention of fungal diseases in liver transplant recipients
Detailed description
A number of well characterized risk factors have been shown to portend a high risk of opportunistic mycoses after liver transplantation. Retransplantation and renal failure are amongst the most significant risk factors for invasive fungal infections in these patients. Most Invasive fungal infections in these high-risk patients occur within the first month posttransplant. Studies utilizing universal prophylaxis have primarily employed fluconazole. A recent meta-analysis of prophylactic trials documented a beneficial effect on morbidity and attributable mortality, but an emergence of infections due to non-albicans Candida spp. in patients receiving prophylaxis. The availability of echinocandins has led to an expanded armamentarium of antifungal drugs with a potentially promising role as agents for targeted prophylaxis for invasive fungal infections in high-risk liver transplant recipients. Anidulafungin is unique amongst echinocandins in that it is eliminated from the body almost exclusively through biotransformation by slow non-enzymatic degradation in the blood, without hepatic metabolism or renal elimination. Anidulafungin has demonstrated good safety profile. We hypothesize that anidulafungin will be more effective and a better tolerated antifungal prophylactic agent in this setting.
Interventions
DRUGAnidulafungin
200 mg IV loading dose followed by 100 mg qd for 21 days
DRUGFluconazole
400 mg IV for 21 days
Sponsors
University of Pittsburgh
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Liver transplant recipient at increased risk for infection increased risk include any of the following: * retransplantation * renal replacement therapy (dialysis), * post transplant abdominal surgery (within 21days) * receipt of corticosteroids for greater than 14 days within the 4 weeks -preceding transplant * ICU care for greater than 48 hours at the time of transplantation * colonization with Candida sps within 4 weeks of transplantation * requirement of 15 units or greater of packed red cell transfusions * Intraoperative time exceeding 6 hours
Exclusion criteria
* Hypersensitivity to azole or echinocandin antifungal agents * receipt of systemic antifungal therapy within 4 weeks prior to transplantation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Frequency of Fungal Infection | 90 days post enrollment |
Secondary
| Measure | Time frame |
|---|---|
| Need for Additional Antifungal Therapy | 90 days post enrollment |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Anidulafungin anti-fungal agent
Anidulafungin: 200 mg IV loading dose followed by 100 mg qd for 21 days | 100 |
| Fluconazole anti-fungal agent
Fluconazole: 400 mg IV for 21 days | 100 |
| Total | 200 |
Baseline characteristics
| Characteristic | Anidulafungin | Fluconazole | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 11 Participants | 11 Participants | 22 Participants |
| Age, Categorical Between 18 and 65 years | 89 Participants | 89 Participants | 178 Participants |
| Age, Continuous | 58 years | 58 years | 58 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 27 Participants | 38 Participants | 65 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 73 Participants | 62 Participants | 135 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 100 participants | 100 participants | 200 participants |
| Sex: Female, Male Female | 33 Participants | 28 Participants | 61 Participants |
| Sex: Female, Male Male | 67 Participants | 72 Participants | 139 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 98 | 11 / 99 |
| serious Total, serious adverse events | 1 / 98 | 0 / 99 |
Outcome results
Primary
Frequency of Fungal Infection
Time frame: 90 days post enrollment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anidulafungin | Frequency of Fungal Infection | 5 participants |
| Fluconazole | Frequency of Fungal Infection | 8 participants |
Secondary
Need for Additional Antifungal Therapy
Time frame: 90 days post enrollment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anidulafungin | Need for Additional Antifungal Therapy | 11 participants |
| Fluconazole | Need for Additional Antifungal Therapy | 11 participants |