A Post Marketing Surveillance Study of Lipo-AB® (Amphotericin B) in Neutropenic Patients With Persistent Fever

Study Overview
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Brief Summary
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Amphotericin B is a polyene antifungal drug used for the treatment of many systemic fungal infections. It is associated with many side effects which in some cases can be very severe and potentially lethal. Lipo-AB® is a true single bilayer liposomal drug delivery system, consisting of unilamellar bilayer liposomes with amphotericin B intercalated within the membrane. Prior studies showed that the liposomal formulation of amphotericin B greatly reduces the side effects of the parent drug, such as nephrotoxicity. This study is designed to evaluate the safety and efficacy of Lipo-AB® in neutropenic patients with persistent fever in routine clinical practice in Taiwan. Primary objective: • To evaluate the nephrotoxicity of Lipo-AB® (amphotericin B) treatment in neutropenic patients with persistent fever in Taiwan clinical practice. Secondary objectives: (1) To evaluate the safety profile of Lipo-AB® (amphotericin B) in neutropenic patients with persistent fever in Taiwan clinical practice. (2) To evaluate the treatment efficacy of Lipo-AB® (amphotericin B) in neutropenic patients with persistent fever in Taiwan clinical practice.

Official Title
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A Post Marketing Surveillance Study of Lipo-AB® (Amphotericin B) in Neutropenic Patients With Persistent Fever

Conditions
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Neutropenia, Febrile

Intervention / Treatment
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* Drug: Lipo-AB® (amphotericin B) liposome


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female or male with no age limit Patient for whom Lipo-AB® is medically recommended due to following conditions: Absolute neutrophil count (ANC) < 500/mm3 for at least 96 hours Received parenteral broad spectrum antibacterial therapy for at least 96 hours Fever of ≥ 38.0°C (tympanic temperature) Subject or his/her legally acceptable representative is willing and able to provide a written informed consent Exclusion Criteria: Pregnant female, with the exception of those for whom the possible benefits to be derived outweigh the potential risks involved Use of other investigational product 2 weeks before the initiation of Lipo-AB® treatment which is considered not suitable for this study by investigator Use of any parenteral antifungals for current infection which is not considered treatment failure (either intolerance to the drug or lack of response) Any condition which is considered not suitable for liposomal amphotericin B therapy by investigator
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Lipo-AB® (amphotericin B) liposome|Name: Lipo-AB® (amphotericin B) liposome for injection Dosage form: Lyophilized powder 50 mg/vial Dose: Based on approved package insert and physician's discretion Recommended initial dose: 3 mg/kg/day Dosing schedule: All patients will receive Lipo-AB® based on the approved package insert and physician's clinical decision.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence rate of nephrotoxicity | * Nephrotoxicity is defined as serum creatinine (SCr) values increasing 100% or more over pretreatment levels in pediatric patients, and creatinine values increasing 100% or more over pretreatment levels in adult patients provided the peak creatinine concentration was > 1.2 mg/dL during treatment period. ** The nephrotoxicity associated with baseline SCr will also be assessed. | through Observation period (up to 44 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Categorization of the change in renal function | SCr < 1.5 x baseline SCr (BSC) SCr ≥ 1.5 x BSC SCr ≥ 2 x BSC SCr ≥ 3 x BSC | through Observation period (up to 44 days) | 
| Change in laboratory parameters (1) | hemoglobin (Hb in g/dL) | through Observation period (up to 44 days) | 
| Change in laboratory parameters (2) | hematocrit (Hct in %) | through Observation period (up to 44 days) | 
| Change in laboratory parameters (3) | red blood cell (RBC in 10^6/uL) | through Observation period (up to 44 days) | 
| Change in laboratory parameters (4) | white blood cell (WBC in 10^3/uL) | through Observation period (up to 44 days) | 
| Change in laboratory parameters (5) | ANC (absolute neutrophil count in mm^3) | through Observation period (up to 44 days) | 
| Change in laboratory parameters (6) | platelet count in 10^3/uL | through Observation period (up to 44 days) | 
| Change in laboratory parameters (7) | alanine aminotransferase (ALT in U/L) | through Observation period (up to 44 days) | 
| Change in laboratory parameters (8) | aspartate aminotransferase (AST in U/L) | through Observation period (up to 44 days) | 
| Change in laboratory parameters (9) | total bilirubin (TB in mg/dL) | through Observation period (up to 44 days) | 
| Change in laboratory parameters (10) | BUN in mg/dL | through Observation period (up to 44 days) | 
| Change in laboratory parameters (11) | serum creatinine (SCr in mg/dL) | through Observation period (up to 44 days) | 
| Change in laboratory parameters (12) | glucose (mg/dL) | through Observation period (up to 44 days) | 
| Change in laboratory parameters (13) | Na (mmol/L) | through Observation period (up to 44 days) | 
| Change in laboratory parameters (14) | K (mmol/L) | through Observation period (up to 44 days) | 
| Change in laboratory parameters (15) | Mg (mg/dL) | through Observation period (up to 44 days) | 
| Change in laboratory parameters (16) | Ca (mg/dL) | through Observation period (up to 44 days) | 
| Change in laboratory parameters (17) | Urine protein (mg/dL) | through Observation period (up to 44 days) | 
| Change in vital signs (1) | systolic/diastolic blood pressure (SBP/ DBP in mmHg) | through Observation period (up to 44 days) | 
| Change in vital signs (2) | pulse rate (PR in bpm) | through Observation period (up to 44 days) | 
| Change in vital signs (3) | tympanic temperature (TT in °C) | through Observation period (up to 44 days) | 
| Adverse event(s) | Hypokalemia, Hypomagnesemia, Hypocalcemia, Hypernatremia, Hyponatremia, Infusion-related reaction(s) (IRR), Other adverse event(s). | through Observation period (up to 44 days) | 
| Overall success rate | Defined as a composite of five criteria: Survival for 7 days after completion of the observational treatment Fever resolved during neutropenic period: defined as a tympanic temperature < 38°C for at least 48 hours Baseline fungal infection cured (if present): defined as (i) resolution of all attributable clinical symptoms and signs of fungal infection during the observational period, (ii) negative microbiological result at the EOT (end of treatment), if available No breakthrough fungal infections (proved, probable and possible) during administration of the observational drug or within 7 days after the completion of observational treatment Absence of premature discontinuation of the observational drug because of toxicity or lack of efficacy | through Observation period (up to 44 days) | 
| Overall survival rate |  | through Observation period (up to 44 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Amphotericin B, liposome, post marketing surveillance