Study type

Study topic

Human medicinal product

Study type

Non-interventional study

Scope of the study

Assessment of risk minimisation measure implementation or effectiveness

Data collection methods

Secondary use of data
Non-interventional study

Non-interventional study design

Cohort
Study drug and medical condition

Anatomical Therapeutic Chemical (ATC) code

(D01B) ANTIFUNGALS FOR SYSTEMIC USE
ANTIFUNGALS FOR SYSTEMIC USE
Population studied

Short description of the study population

Patients were identified by their first PAF use during a hospitalization between January 1, 2005 and December 31, 2012.
All exclusions were applied to create a single study population for analyses. Patients were excluded if they had earlier recorded PAF use, if they started use of micafungin and a different PAF on the same day, had pre-existing chronic hepatic or renal disease, had both no ALT and no AST or had no bilirubin or had no serum creatinine test results recorded in the 30 days prior to and including PAF initiation. Patients were removed if their last preceding AST or ALT in the 30 days prior to and including PAF initiation were more than five times the local upper limit of normal (ULN), or if their last ALT value was greater than 300 U/L, or if their last AST was greater than 200 U/L, or if their last preceding bilirubin was more than three times the local ULN. Patients were required to have no record of having received dialysis in the 30 days prior to and including cohort entry.
Patients were excluded from the cohort if their last preceding eGFR was <30 ml/min in the 30 days prior to and including PAF initiation. Patients were also excluded if they had no bilirubin, creatinine, or neither ALT nor AST during follow-up.

Age groups

Preterm newborn infants (0 – 27 days)
Term newborn infants (0 – 27 days)
Infants and toddlers (28 days – 23 months)
Children (2 to < 12 years)
Adolescents (12 to < 18 years)
Adults (18 to < 46 years)
Adults (46 to < 65 years)
Adults (65 to < 75 years)
Adults (75 to < 85 years)
Adults (85 years and over)

Special population of interest

Immunocompromised

Estimated number of subjects

35000
Study design details

Main study objective

This multicenter observational cohort study proposes to establish the risks of short and long-term outcomes in users of parenteral micafungin and in users of other parenteral antifungal agents from 2005 through 2012 with follow-up until 2016.

Outcomes

Three 30-day outcomes (a, b, and c) and one long-term outcome (d) identified during up to 12 years following treatment. a. Treatment-emergent hepatic injury or dysfunctionb. Treatment-emergent renal failure or dysfunctionc. Rehospitalization for the parenteral treatment of fungal infectionsd. Death from hepatocellular carcinoma (HCC)

Data analysis plan

Study outcomes will be identified in the short term (up to 30 days) and the long term (up to 12 years).Survival analysis will compare the occurrence of each 30-day outcome among the parenteral antifungal agents and will employ multivariate propensity score methods to adjust for possible confounding effects of age, gender, race, and comorbid conditions . A further assessment of potential for residual effects due to patient characteristics obtained through chart review of cases and a random sample of the cohort will be conducted. The occurrence of the long-term outcome (HCC mortality) will analogously employ survival analysis and propensity score techniques.