An Observational Analysis of Voriconazole Therapeutic Drug Concentration Monitoring, Pharmacogenomics and Clinical Outcome Correlations in High-risk Hematology Patients

A Prospective, Observational Analysis of Voriconazole (VOR) Therapeutic Drug Concentration Monitoring, Pharmacogenomics and Clinical Outcome Correlations in High-risk Hematology Patients at Princess Margaret Hospital

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT01321372

Enrollment

Registered

2011-03-23

Start date

2007-06-30

Completion date

2011-06-30

Last updated

2013-03-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Acute Leukemia

Brief summary

Hematology patients are at high risk for invasive fungal infection (IFI) and are being treated with voriconazole (VOR) at Princess Margaret Hospital (PMH). It is critical that patients' serum drug levels are within therapeutic ranges when undergoing treatment. The primary objective of this study is to determine whether clinical responses (complete/partial/failure) directly correlate with patients' blood VOR drug levels. In patients whose disease progression is associated with inadequate voriconazole (VOR) drug levels, serum drug level determination can allow for dose adjustment, thereby preventing disease progression. Patients who are extensive metabolizers may have subtherapeutic VOR levels leading to treatment failure whereas, poor metabolizers may have high drug levels that cause toxicity. Isoenzyme such as CYP2C19 exhibits genetic polymorphism. Genotyping tests can also be helpful in determining patient risk subjecting to extreme spectrum of drug levels.

Interventions

None listed

Study design

Observational model

COHORT

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Healthy volunteers

Inclusion criteria

* Acute leukemia (including myelogenous and lymphocytic) patients for remission induction chemotherapy, reinduction chemotherapy and consolidation chemotherapy whose antifungal treatment include voriconazole. * Patients have been subscribed voriconazole for probable or proven fungal infections by microbiological/cytohistological evidence from fine needle aspirate or bronchoalveolarlavage means. * Patients will also have imaging positive from lose dose CT results depicting halo signs or crescent signs suggestive of invasive fungal infections. * Patients must be able to tolerate oral intake of medications.

Exclusion criteria

* Patients unable to tolerate oral administration with any combinations of severe mucositis (\> or = grade 3), nausea/vomiting (\> or = grade 3), diarrhea (\> or =grade 2), neutropenic enterocolitis (\> or = grade3).

Design outcomes

Primary

Measure	Time frame	Description
To determine whether clinical responses (complete/partial/failure) directly correlate with patients' blood voriconazole levels.	4 years	The primary outcome measure is defined by the following endpoints: 1. abefrile for at least 48 hours 2. no breakthrough fungal infection 3. resolution or improvement of radiological findings

Secondary

Measure	Time frame	Description
The secondary objective of this study will focus on clinical toxicity, organ involvement and survival.	4 years	The secondary outcome of the study is defined as resolution of renal or hepatic dysfunction and survival.

Countries

Canada

Outcome results