Fungal Infection, Liver Transplant Infection
Conditions
Keywords
rezafungin, liver transplant, prophylaxis
Brief summary
This is an interventional study to evaluate the efficacy of rezafungin, a new echinocandin, for the prevention of invasive fungal infections (IFIs) after liver transplantation. Patients who receive rezafungin will be compared to a similar group of patients who underwent liver transplantation in the preceding two years for the incidence of IFIs.
Detailed description
This is a single arm interventional study of consecutive liver transplant recipients who have consented to this rezafungin prophylaxis study. The outcome will be compared with that of similar group of patients not enrolled in the study and those who underwent liver transplant in the preceding two years (historical controls). Propensity score matching will be used to select retrospective cohort. There will be 3 groups: 1. Study group (prospective intervention cohort): Rezafungin (180 patients) 2. Prospective control group (prospective control cohort): Patients who receive fluconazole/voriconazole or no antifungal prophylaxis as part of UPMC's tiered antifungal prophylaxis standard of care (20 patients: 10 who receive fluconazole/voriconazole and 10 who do not receive fluconazole/voriconazole) 3. Historical control group (retrospective control cohort): Patients at risk for IFI who received fluconazole/voriconazole (tier approach) in the two years preceding this study (180 patients)
Interventions
DRUGRezafungin
Rezafungin 400 mg IV once within 24 hours of liver transplant, followed by 200 mg IV weekly for 4 weeks.
DRUGStandard of care antifungal prophylaxis
UPMC uses a tiered approach to antifungal prophylaxis, based on risk factors for IFI. Fluconazole is used for recipients with risk factors for yeast infections: choledochojejunostomy, prolonged transplant time, receipt of \>40 units of blood products within 24 hours of transplant, and Candida colonization or infection within 3 months prior to transplant. Voriconazole is used for recipients with risk factors for mould infections: re-transplantation, renal failure requiring renal replacement therapy, fulminant hepatic failure as indication for transplant, intra-abdominal/thoracic re-exploration within the first month after transplant. No prophylaxis is given if there are no risk factors for yeast or mould infections.
Sponsors
Melinta Therapeutics
Fernanda P Silveira, MD, MS
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
Interventional, open-label, single center study with concurrent and historical controls
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Liver transplant recipient * 18 years of age or older * ≥1 risk factor(s) for IFI: living donor transplant, retransplantation, complicated operations (based on duration of transplant and number of blood products required in the peri-transplant period), choledochojejunostomy anastomosis, or peri-operative Candida colonization, recent Candida infection, renal replacement therapy post-transplant, and reoperation within the first 90 days of transplant.
Exclusion criteria
* Participants who are perceived not to survive past 7 days after transplant * Participants who elect not to participate in the prospective trial * Participants who had active candidiasis at the time of transplant * Participants with a history of allergy to an echinocandin * Participants who are pregnant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of proven and probable IFIs | 90 days post-transplant | Incidence of proven and probable IFIs within 90 days post-transplant |
| Incidence of proven and probable breakthrough IFI | While receiving rezafungin, voriconazole, or fluconazole | Incidence of breakthrough IFI while on specific antifungal prophylaxis |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fungal colonization | 90 days and 6 months post-transplant | Number of participants with presence or growth of fungi without it causing active infection or disease |
| Graft rejection | 90 days and 6 months post-transplant | Number of participants with liver allograft acute rejection |
| All-cause mortality | 90 days 6 months post-transplant | Number of participants who die |
| Number of participants with premature discontinuation of prophylaxis | 90 days post-transplant | Number of patients who experience an adverse event requiring premature discontinuation of antifungal prophylaxis |
| Overall incidence of development of antifungal resistance | Within 6 months of transplant | Antifungal resistance of breakthrough fungal organisms or fungal organisms recovered within the first 6 months of transplant for patients who received rezafungin |
| Graft loss | 90 days 6 months post-transplant | Number of participants with failure of the liver allograft to function adequately or to remain viable |
| Fungal-free survival | 90 days and 6 months post-transplant | Number of participants without fungal infection |
Other
| Measure | Time frame | Description |
|---|---|---|
| Pharmakokinectics (PK) of rezafungin | Up to 4 weeks post-transplant | Pharmacokinetics of rezafungin while in ICU to assess the PK during the peri-transplant period |
| Stool microbiota composition | Within 6 months post-transplant | Stool microbiota and fecal Candida constituent and susceptibility profile in response to rezafungin |
Countries
United States
Outcome results
None listed