Invasive Fungal Infection
Conditions
Keywords
voriconazole, invasive pulmonary aspergillosis, hematologic malignancy, therapeutic drug monitoring, genetic polymorphism, efficacy, safety
Brief summary
Multiple factors are associated with a large variability in voriconazole exposure following standard dose administration, such as non-linear saturable pharmacokinetics, drug-drug interactions, liver disease, patient age, and genetic polymorphism of the metabolic enzymes. Voriconazole is extensively metabolized by the human hepatic enzymes, primarily mediated by CYP2C19. The polymorphisms account for a relatively large portion of inter-individual variance observed in voriconazole plasma concentrations. However, there are limited data on the relationships between voriconazole blood levels and clinical outcomes or safety in Asian populations. The purpose of this study is to investigate the relationships of voriconazole blood levels with genetic polymorphism, safety, and clinical outcomes in immunocompromised patients with invasive pulmonary aspergillosis.
Detailed description
The investigators are trying to establish that routine clinical practice for voriconazole therapeutic drug monitoring can improve the efficacy and safety outcomes. In Korean patients with hematologic malignancy, the investigators also want to propose the optimal dosing guideline of voriconazole with different genetic polymorphisms.
Interventions
DRUGvoriconazole
intravenous, oral administration
Sponsors
Asan Medical Center
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
15 Years to No maximum
Healthy volunteers
No
Inclusion criteria
all items below * male or female ≥ 15 years of age * immunocompromised patients with hematologic disorders * patients received voriconazole due to treat proven, probable invasive (pulmonary) aspergillosis
Exclusion criteria
* severe hepatic dysfunction (t.bil, AST, ALT, ALP \> 5 x upper normal limit) * who experienced hypersensitivity to azoles * pregnant women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Successful outcome at 12 weeks after voriconazole use | 12 weeks | Successful outcome = complete response + partial response Unsuccessful outcome = stable disease + failure of therapy + indeterminate response |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| IFI (invasive fungal infection)-related mortality at 12 weeks | 12 weeks | IFI (invasive fungal infection)-related mortality at 12 weeks |
| Successful outcomes at various time points | 1 week, 2 weeks, 4 weeks, and 8 weeks | Successful outcomes at 1 week,2 weeks,4 weeks, and 8 weeks after voriconazole use |
| Non-IFI (invasive fungal infection)-related mortality at 12 weeks | 12 weeks | Non-IFI (invasive fungal infection)-related mortality at 12 weeks |
| breakthrough IFI | 12 weeks | breakthrough IFI |
| Adverse drug reactions | 12 weeks | Adverse drug reactions (liver function test impairment, visual disturbance, hallucination, photosensitive rash, renal impairment) |
Countries
South Korea
Outcome results
None listed