Rezafungin Prophylaxis in Liver Transplant

NCT ID: NCT06774144

Last Updated: 2025-10-17

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Clinical Phase: PHASE3
• Total Enrollment: 385 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-10-15
• Study Completion Date: 2028-12-31

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)

Conditions

Liver Transplant Infection; Fungal Infection

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Rezafungin

Intervention Type: DRUG

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

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

Group Type: ACTIVE_COMPARATOR

Standard of care antifungal prophylaxis

Intervention Type: DRUG

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.

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

Group Type: ACTIVE_COMPARATOR

Standard of care antifungal prophylaxis

Intervention Type: DRUG

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.

Interventions

Rezafungin

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

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Fluconazole, voriconazole, or no prophylaxis

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Melinta Therapeutics

INDUSTRY

Sponsor Role: collaborator

Fernanda P Silveira, MD, MS

OTHER

Sponsor Role: lead

Responsible Party

Fernanda P Silveira, MD, MS

Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Fernanda Silveira

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

UPMC Presbyterian

Pittsburgh, Pennsylvania, United States

Countries

United States

Other Identifiers

STUDY24080165

Identifier Type: -

Identifier Source: org_study_id