Liposomal Amphotericin B for Invasive Fungal Disease in Solid Organ Transplant Recipients

Official title

A Real-World Observational Study of the Effectiveness, Safety, and Therapeutic Drug Monitoring of Liposomal Amphotericin B in Solid Organ Transplant Recipients With Invasive Fungal Disease

Overview

This real-world observational study aims to evaluate the effectiveness, safety, and therapeutic drug monitoring (TDM) of liposomal amphotericin B (L-AmB) in solid organ transplant recipients with invasive fungal disease (IFD). IFD is a major cause of morbidity and mortality in transplant recipients because of long-term immunosuppressive therapy and increased susceptibility to opportunistic fungal infections. This is a single-center ambispective cohort study conducted at Sichuan Provincial People's Hospital. The study includes a prospective cohort of solid organ transplant recipients receiving L-AmB therapy and a historical control cohort treated with alternative systemic antifungal regimens. Clinical management and treatment decisions will be determined by treating physicians according to routine clinical practice, and no study-specific intervention will be introduced. The study will collect information on demographic characteristics, transplant type, immunosuppressive regimens, fungal pathogens, infection sites, antifungal treatment strategies, laboratory findings, and clinical outcomes. Particular attention will be given to renal safety, electrolyte abnormalities, and therapeutic drug monitoring of liposomal amphotericin B. Plasma concentrations of L-AmB, treatment modifications, temporary treatment discontinuation, and concentration-related safety and effectiveness outcomes will be recorded during antifungal therapy. The primary outcomes are the 28-day clinical response rate and 84-day all-cause mortality. Secondary outcomes include mycological clearance, acute kidney injury, electrolyte abnormalities, breakthrough fungal infection, treatment discontinuation due to adverse events, liposomal amphotericin B plasma concentrations, and the associations between L-AmB exposure and clinical outcomes or treatment-related toxicities. The study is expected to provide real-world evidence regarding the effectiveness, safety, and pharmacokinetic characteristics of L-AmB in transplant recipients, support optimization of antifungal treatment strategies, and inform individualized dosing and monitoring approaches in this high-risk population.

Interventions

• Drug Liposomal Amphotericin B
  Liposomal amphotericin B administered for treatment of proven, probable, or possible invasive fungal disease in solid organ transplant recipients according to routine clinical practice. Dose adjustment and treatment duration are determined by treating physicians.
• Drug Alternative Systemic Antifungal Therapy
  Alternative systemic antifungal agents including azoles, echinocandins, or other standard antifungal therapies administered according to routine clinical practice in historical control patients with invasive fungal disease.

Primary outcome measures

• 28-Day Clinical Response Rate [Time frame: Day 28]
• 84-Day All-Cause Mortality [Time frame: Day 84]

Secondary outcome measures (8)

• Mycological Clearance Rate [Time frame: Day 28]
• Acute Kidney Injury [Time frame: Baseline through Day 84]
• Electrolyte Abnormalities [Time frame: Baseline through Day 84]
• Liposomal Amphotericin B Plasma Concentration [Time frame: Baseline through Day 84]
• Association Between Liposomal Amphotericin B Exposure and Clinical Response [Time frame: Baseline through Day 84]
• Association Between Liposomal Amphotericin B Exposure and Adverse Events [Time frame: Baseline through Day 84]
• Breakthrough Fungal Infection [Time frame: Baseline through Day 84]
• Antifungal Treatment Discontinuation Due to Adverse Events [Time frame: Baseline through Day 84]

Eligibility criteria

Inclusion criteria

• Age 18 to 75 years.
• Recipient of a solid organ transplant.
• Diagnosis of invasive fungal disease (IFD) according to EORTC/MSGERC criteria.
• Receiving liposomal amphotericin B therapy as part of routine clinical care.
• Provision of informed consent for prospective participants.

Exclusion criteria

• Known hypersensitivity to amphotericin B formulations.
• Severe hepatic dysfunction (ALT or AST >5× upper limit of normal, or total bilirubin >2× upper limit of normal).
• Severe renal dysfunction requiring permanent discontinuation of antifungal therapy at baseline.
• Pregnancy or breastfeeding.
• Participation judged inappropriate by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

China · 1 center

• Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital — Chengdu

Publications

• Donnelly JP, Chen SC, Kauffman CA, Steinbach WJ, Baddley JW, Verweij PE, Clancy CJ, Wingard JR, Lockhart SR, Groll AH, Sorrell TC, Bassetti M, Akan H, Alexander BD, Andes D, Azoulay E, Bialek R, Bradsher RW, Bretagne S, Calandra T, Caliendo AM, Castagnola E, Cruciani M, Cuenca-Estrella M, Decker CF, Desai SR, Fisher B, Harrison T, Heussel CP, Jensen HE, Kibbler CC, Kontoyiannis DP, Kullberg BJ, La PMID 31802125

Identifiers

NCT: NCT07656493 · KC2025-JX-0390WLH-06 · KC2025-JX-0390WLH-06

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗