Clinical trial NCT06774144: Rezafungin Prophylaxis in Liver Transplant
Official title: Rezafungin Prophylaxis in Liver Transplant At High Risk for Invasive Fungal Infection
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Liver Transplant Infection
Fungal Infection
Keywords: rezafungin
liver transplant
prophylaxis
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: Melinta Therapeutics
First posted: 2025-01-14
Enrollment: 385
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Interventional, open-label, single center study with concurrent and historical controls
Primary purpose: PREVENTION

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)

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.

Primary outcomes:
measure: Incidence of proven and probable IFIs
timeFrame: 90 days post-transplant
measure: Incidence of proven and probable breakthrough IFI
timeFrame: While receiving rezafungin, voriconazole, or fluconazole
Secondary outcomes:
measure: Fungal-free survival
timeFrame: 90 days and 6 months post-transplant
measure: Fungal colonization
timeFrame: 90 days and 6 months post-transplant
measure: Graft rejection
timeFrame: 90 days and 6 months post-transplant
measure: Graft loss
timeFrame: 90 days 6 months post-transplant
measure: All-cause mortality
timeFrame: 90 days 6 months post-transplant
measure: Number of participants with premature discontinuation of prophylaxis
timeFrame: 90 days post-transplant
measure: Overall incidence of development of antifungal resistance
timeFrame: Within 6 months of transplant
Other outcomes:
measure: Pharmakokinectics (PK) of rezafungin
timeFrame: Up to 4 weeks post-transplant
measure: Stool microbiota composition
timeFrame: Within 6 months post-transplant
Locations:
city: Pittsburgh
country: United States
facility: UPMC Presbyterian
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Fernanda Silveira
role: PRINCIPAL_INVESTIGATOR
References: