Rezafungin Prophylaxis in Liver Transplant

Rezafungin Prophylaxis in Liver Transplant at High Risk for Invasive Fungal Infection

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Liver Transplant Infection; Fungal Infection
• Intervention / Treatment: Drug: Rezafungin; Drug: Standard of care antifungal prophylaxis

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 Type: Interventional
• Enrollment (Estimated): 385
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Presbyterian

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prospective Intervention Cohort; 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	Drug: Rezafungin; Rezafungin 400 mg IV once within 24 hours of liver transplant, followed by 200 mg IV weekly for 4 weeks.
Active Comparator: Prospective Control Cohort; Patients who receive fluconazole/voriconazole or no antifungal prophylaxis as part of UPMC's risk-based antifungal prophylaxis standard of care after liver transplant	Drug: Standard 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.; Other Names: Fluconazole, voriconazole, or no prophylaxis
Active Comparator: Historical Control Group; Patients at risk for IFI who received fluconazole/voriconazole for antifungal prophylaxis after liver transplant in the two years preceding the study	Drug: Standard 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.; Other Names: Fluconazole, voriconazole, or no prophylaxis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of proven and probable IFIs	Incidence of proven and probable IFIs within 90 days post-transplant	90 days post-transplant
Incidence of proven and probable breakthrough IFI	Incidence of breakthrough IFI while on specific antifungal prophylaxis	While receiving rezafungin, voriconazole, or fluconazole

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fungal-free survival	Number of participants without fungal infection	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	90 days and 6 months post-transplant
Graft rejection	Number of participants with liver allograft acute rejection	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	90 days 6 months post-transplant
All-cause mortality	Number of participants who die	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	90 days post-transplant
Overall incidence of development of antifungal resistance	Antifungal resistance of breakthrough fungal organisms or fungal organisms recovered within the first 6 months of transplant for patients who received rezafungin	Within 6 months of transplant

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmakokinectics (PK) of rezafungin	Pharmacokinetics of rezafungin while in ICU to assess the PK during the peri-transplant period	Up to 4 weeks post-transplant
Stool microbiota composition	Stool microbiota and fecal Candida constituent and susceptibility profile in response to rezafungin	Within 6 months post-transplant

Collaborators and Investigators

• Sponsor: Fernanda P Silveira, MD, MS
• Collaborators: Melinta Therapeutics
• Investigators: Principal Investigator: Fernanda Silveira, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: December 18, 2024
• First Submitted That Met QC Criteria: January 8, 2025
• First Posted (Actual): January 14, 2025

Study Record Updates

• Last Update Posted (Actual): October 20, 2025
• Last Update Submitted That Met QC Criteria: October 15, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: prophylaxis; liver transplant; rezafungin
• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Mycoses; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Triazoles; Rezafungin; Fluconazole; Voriconazole
• Other Study ID Numbers: STUDY24080165

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: We do not plan to share individual participant data outside of our investigative team and collaborators. Aggregate data will be shared in publications as appropriate.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No