Invasive Fungal Infection, Opportunistic Infections, Solid Organ Transplantation
Conditions
Keywords
Liposomal Amphotericin B, Solid Organ Transplantation, Invasive Fungal Disease, Antifungal Therapy, Tacrolimus, Cyclosporine, Therapeutic Drug Monitoring, Drug-Drug Interaction, Real-World Study, Transplant Infection
Brief summary
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
DRUGLiposomal 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.
DRUGAlternative 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.
Sponsors
Sichuan Provincial People's Hospital
Beijing Science and Technology Innovation Medical Development Foundation
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 28-Day Clinical Response Rate | Day 28 | Proportion of participants achieving complete or partial clinical response at Day 28 after initiation of antifungal therapy. |
| 84-Day All-Cause Mortality | Day 84 | All-cause mortality occurring within 84 days after initiation of antifungal therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mycological Clearance Rate | Day 28 | Proportion of participants with documented clearance of fungal pathogens. |
| Acute Kidney Injury | Baseline through Day 84 | Occurrence of acute kidney injury during antifungal treatment. |
| Electrolyte Abnormalities | Baseline through Day 84 | Occurrence of hypokalemia, hypomagnesemia, or other treatment-related electrolyte disturbances. |
| Liposomal Amphotericin B Plasma Concentration | Baseline through Day 84 | Plasma concentration of liposomal amphotericin B measured during antifungal therapy. |
| Association Between Liposomal Amphotericin B Exposure and Clinical Response | Baseline through Day 84 | Relationship between liposomal amphotericin B plasma concentration and clinical response. |
| Association Between Liposomal Amphotericin B Exposure and Adverse Events | Baseline through Day 84 | Relationship between liposomal amphotericin B plasma concentration and treatment-related adverse events, including nephrotoxicity and electrolyte abnormalities. |
| Breakthrough Fungal Infection | Baseline through Day 84 | Occurrence of breakthrough invasive fungal infection during antifungal therapy. |
| Antifungal Treatment Discontinuation Due to Adverse Events | Baseline through Day 84 | Permanent discontinuation of antifungal therapy because of treatment-related adverse events. |
Countries
China
Contacts
CONTACTLingai Pan, MD
PRINCIPAL_INVESTIGATORLingai Pan, MD
Sichuan Provincial People's Hospital
Outcome results
None listed