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

Sponsor

TTY Biopharm (Industry)

Overall Status

Completed

CT.gov ID

NCT03511820

Collaborator

(none)

Enrollment

Locations

19.7

Actual Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Neutropenia, Febrile	Drug: Lipo-AB® (amphotericin B) liposome

Study Design

Study Type:

Observational

Actual Enrollment :

54 participants

Observational Model:

Case-Only

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

May 24, 2016

Actual Primary Completion Date :

Jan 15, 2018

Actual Study Completion Date :

Jan 15, 2018

Outcome Measures

Primary Outcome Measures

Incidence rate of nephrotoxicity [through Observation period (up to 44 days)]
* 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.

Secondary Outcome Measures

Categorization of the change in renal function [through Observation period (up to 44 days)]
SCr < 1.5 x baseline SCr (BSC) SCr ≥ 1.5 x BSC SCr ≥ 2 x BSC SCr ≥ 3 x BSC
Change in laboratory parameters (1) [through Observation period (up to 44 days)]
hemoglobin (Hb in g/dL)
Change in laboratory parameters (2) [through Observation period (up to 44 days)]
hematocrit (Hct in %)
Change in laboratory parameters (3) [through Observation period (up to 44 days)]
red blood cell (RBC in 10^6/uL)
Change in laboratory parameters (4) [through Observation period (up to 44 days)]
white blood cell (WBC in 10^3/uL)
Change in laboratory parameters (5) [through Observation period (up to 44 days)]
ANC (absolute neutrophil count in mm^3)
Change in laboratory parameters (6) [through Observation period (up to 44 days)]
platelet count in 10^3/uL
Change in laboratory parameters (7) [through Observation period (up to 44 days)]
alanine aminotransferase (ALT in U/L)
Change in laboratory parameters (8) [through Observation period (up to 44 days)]
aspartate aminotransferase (AST in U/L)
Change in laboratory parameters (9) [through Observation period (up to 44 days)]
total bilirubin (TB in mg/dL)
Change in laboratory parameters (10) [through Observation period (up to 44 days)]
BUN in mg/dL
Change in laboratory parameters (11) [through Observation period (up to 44 days)]
serum creatinine (SCr in mg/dL)
Change in laboratory parameters (12) [through Observation period (up to 44 days)]
glucose (mg/dL)
Change in laboratory parameters (13) [through Observation period (up to 44 days)]
Na (mmol/L)
Change in laboratory parameters (14) [through Observation period (up to 44 days)]
K (mmol/L)
Change in laboratory parameters (15) [through Observation period (up to 44 days)]
Mg (mg/dL)
Change in laboratory parameters (16) [through Observation period (up to 44 days)]
Ca (mg/dL)
Change in laboratory parameters (17) [through Observation period (up to 44 days)]
Urine protein (mg/dL)
Change in vital signs (1) [through Observation period (up to 44 days)]
systolic/diastolic blood pressure (SBP/ DBP in mmHg)
Change in vital signs (2) [through Observation period (up to 44 days)]
pulse rate (PR in bpm)
Change in vital signs (3) [through Observation period (up to 44 days)]
tympanic temperature (TT in °C)
Adverse event(s) [through Observation period (up to 44 days)]
Hypokalemia, Hypomagnesemia, Hypocalcemia, Hypernatremia, Hyponatremia, Infusion-related reaction(s) (IRR), Other adverse event(s).
Overall success rate [through Observation period (up to 44 days)]
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
Overall survival rate [through Observation period (up to 44 days)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Changhua Christian Hospital	Changhua	Taiwan	500
2	Kaohsiung Veterans General Hospital	Kaohsiung	Taiwan	81362
3	Kaohsiung Chang Gung Memorial Hospital	Kaohsiung	Taiwan	833
4	Keelung Chang Gung Memorial Hospital	Keelung	Taiwan	204
5	China Medical University Hospital	Taichung City	Taiwan	40447
6	Tri-Service General Hospital	Taipei city	Taiwan	114
7	Taipei Veterans General Hospital	Taipei	Taiwan	11212
8	Taipei Mucinipal Wanfang Hospital	Taipei	Taiwan	116
9	Chang Guang Memorial Hospital at LinKou	Taoyuan	Taiwan	333