Rezafungin Prophylaxis in Liver Transplant

Phase 3

Not yet recruiting

• Conditions: Liver Transplant Infection; Fungal Infection
• Interventions: Drug: Standard of care antifungal prophylaxis; Drug: Rezafungin

• Registration Number: NCT06774144
• Lead Sponsor: Fernanda P Silveira, MD, MS

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)

Study Timeline

• Study First Submitted: 2024-12-18
• Status Verified: 2025-01
• Study First Submitted QC: 2025-01-08
• Study First Posted: 2025-01-14
• Last Update Submitted: 2025-03-03
• Last Update Posted: 2025-03-04
• Study Start: 2025-06
• Primary Completion: 2028-12
• Study Completion: 2028-12

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 385

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Prospective Control Cohort	Standard of care antifungal prophylaxis	Patients who receive fluconazole/voriconazole or no antifungal prophylaxis as part of UPMC's risk-based antifungal prophylaxis standard of care after liver transplant
Prospective Intervention Cohort	Rezafungin	Rezafungin 400 mg IV once within 24 hours of liver transplant, followed by 200 mg IV once weekly for a total duration of 4 weeks
Historical Control Group	Standard of care antifungal prophylaxis	Patients at risk for IFI who received fluconazole/voriconazole for antifungal prophylaxis after liver transplant in the two years preceding the study

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Fungal-free survival	90 days and 6 months post-transplant	Number of participants without fungal infection
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
Graft loss	90 days 6 months post-transplant	Number of participants with failure of the liver allograft to function adequately or to remain viable
All-cause mortality	90 days 6 months post-transplant	Number of participants who die
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
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

Trial Locations

Locations (1)

UPMC Presbyterian; 🇺🇸 Pittsburgh, Pennsylvania, United States