Rezafungin Prophylaxis in Liver Transplant

Phase 3Enrolling By InvitationNCT06774144

Fernanda P Silveira, MD, MS385 enrolled

Overview

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.

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)

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

385

Conditions

Liver Transplant Infection Fungal Infection

Interventions

RezafunginDRUG

Rezafungin 400 mg IV once within 24 hours of liver transplant, followed by 200 mg IV weekly for 4 weeks.

Standard of care antifungal prophylaxisDRUG

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (1)

UPMC Presbyterian

Pittsburgh, Pennsylvania, United States

Outcomes

Primary Outcomes

Incidence of proven and probable IFIs

Incidence of proven and probable IFIs within 90 days post-transplant

Time frame: 90 days post-transplant

Incidence of proven and probable breakthrough IFI

Incidence of breakthrough IFI while on specific antifungal prophylaxis

Time frame: While receiving rezafungin, voriconazole, or fluconazole

Secondary Outcomes

Fungal-free survival

Number of participants without fungal infection

Time frame: 90 days and 6 months post-transplant

Fungal colonization

Number of participants with presence or growth of fungi without it causing active infection or disease

Time frame: 90 days and 6 months post-transplant

Graft rejection

Number of participants with liver allograft acute rejection

Time frame: 90 days and 6 months post-transplant

Graft loss

Number of participants with failure of the liver allograft to function adequately or to remain viable

Time frame: 90 days 6 months post-transplant

All-cause mortality

Number of participants who die

Time frame: 90 days 6 months post-transplant

Number of participants with premature discontinuation of prophylaxis

Number of patients who experience an adverse event requiring premature discontinuation of antifungal prophylaxis

Data from ClinicalTrials.gov

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