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

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.

1. Primary objective:

   • To evaluate the nephrotoxicity of Lipo-AB® (amphotericin B) treatment in neutropenic patients with persistent fever in Taiwan clinical practice.

2. 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.

Study Overview

• Status: Completed
• Conditions: Neutropenia, Febrile
• Intervention / Treatment: Drug: Lipo-AB® (amphotericin B) liposome

• Study Type: Observational
• Enrollment (Actual): 54

Contacts and Locations

Study Locations

• Taiwan
  • Changhua, Taiwan, 500
    • Changhua Christian Hospital
  • Kaohsiung, Taiwan, 81362
    • Kaohsiung Veterans General Hospital
  • Kaohsiung, Taiwan, 833
    • Kaohsiung Chang Gung Memorial Hospital
  • Keelung, Taiwan, 204
    • Keelung Chang Gung Memorial Hospital
  • Taichung City, Taiwan, 40447
    • China Medical University Hospital
  • Taipei, Taiwan, 11212
    • Taipei Veterans General Hospital
  • Taipei, Taiwan, 116
    • Taipei Mucinipal Wanfang Hospital
  • Taipei city, Taiwan, 114
    • Tri-Service General Hospital
  • Taoyuan, Taiwan, 333
    • Chang Guang Memorial Hospital at LinKou

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Neutropenic patients with persistent fever who are recommended to receive systemic antifungal therapy based on physician's decision will be invited to participate in this study.

Description

Inclusion Criteria:

1. Female or male with no age limit

2. 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)
3. Subject or his/her legally acceptable representative is willing and able to provide a written informed consent

Exclusion Criteria:

1. Pregnant female, with the exception of those for whom the possible benefits to be derived outweigh the potential risks involved
2. Use of other investigational product 2 weeks before the initiation of Lipo-AB® treatment which is considered not suitable for this study by investigator
3. Use of any parenteral antifungals for current infection which is not considered treatment failure (either intolerance to the drug or lack of response)
4. Any condition which is considered not suitable for liposomal amphotericin B therapy by investigator

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: TTY Biopharm

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2016
• Primary Completion (Actual): January 15, 2018
• Study Completion (Actual): January 15, 2018

Study Registration Dates

• First Submitted: April 1, 2018
• First Submitted That Met QC Criteria: April 18, 2018
• First Posted (Actual): April 30, 2018

Study Record Updates

• Last Update Posted (Actual): April 30, 2018
• Last Update Submitted That Met QC Criteria: April 18, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Amphotericin B; liposome; post marketing surveillance
• Additional Relevant MeSH Terms: Hematologic Diseases; Agranulocytosis; Leukopenia; Leukocyte Disorders; Neutropenia; Febrile Neutropenia; Anti-Infective Agents; Anti-Bacterial Agents; Antifungal Agents; Antiprotozoal Agents; Antiparasitic Agents; Amebicides; Amphotericin B; Liposomal amphotericin B
• Other Study ID Numbers: TTYLA1201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No