The Influence of CYP2C19 Polymorphisms on the Safety and Efficacy of Voriconazole
1 other identifier
observational
34
1 country
1
Brief Summary
Voriconazole is a drug used to treat invasive fungal infections. The amount of voriconazole in a person's blood helps to determine how effectively it treats an infection, and how safe it is. Patients respond differently when receiving the same dose - some clearly benefit, other patients experience side effects, and others see limited improvement in their infection. Voriconazole is broken down in the liver mainly by an enzyme called CYP2C19, before being excreted from the body. The activity of CYP2C19 differs between people because of variation in the DNA that encodes the body's instructions to make CYP2C19. If CYP2C19 activity is very high, voriconazole blood levels may remain below the target range when a patient receives a standard dose of voriconazole, which may be insufficient to treat their infection. By contrast, decreased CYP2C19 activity due to genetic variation may result in excessively high voriconazole blood levels, predisposing to serious side effects. Therefore, knowing a patient's CYP2C19 genetic makeup is very important for predicting their response to voriconazole. Thus, the investigators aim to determine the influence of genetic variation in CYP2C19 on the frequency and severity of side effects related to voriconazole, and on the effectiveness of voriconazole for treating serious fungal infections. The findings from this study will contribute to determining the optimal dose of voriconazole that patients with different genetic variants in CYP2C19 should be started on, and will take us one step closer to both understanding the genetic structure of CYP2C19 in the Turkish population, and to 'personalised medicine'.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for all trials
Started Nov 2019
Typical duration for all trials
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
November 1, 2019
CompletedFirst Submitted
Initial submission to the registry
September 7, 2020
CompletedFirst Posted
Study publicly available on registry
September 14, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
October 31, 2022
CompletedSeptember 16, 2020
September 1, 2020
2.2 years
September 7, 2020
September 14, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Frequency and severity of voriconazole related adverse drug reactions
Voriconazole related adverse drug reactions of grade 3-5 systematically evaluated using Liverpool Causality Assessment Tool identified during study follow up. Severity of all adverse events will be graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0
Follow up period for primary outcome is 30 days for each participant
Secondary Outcomes (3)
Non-response to voriconazole
Follow up period for this outcome is 60 days for each participant
Voriconazole trough concentration
30 minutes before the 9th dose of voriconazole
Survival
On days 30 and 60
Study Arms (1)
Voriconazole
All eligible patients will be followed up for voriconazole related adverse drug events and efficacy
Interventions
This is an observational study and only the patients already on voriconazole treatment will be included in the study.
Eligibility Criteria
Patients aged 18 and over that are hospitalized in Dokuz Eylul University Hospital Hematology Service due to a hematological malignancy, and are receiving voriconazole for the management of IFI, which is diagnosed based on EORTC/MSG criteria
You may qualify if:
- ≥ 18 years old
- Receiving voriconazole for the treatment of an invasive fungal infection (IFI) and are within the first five days of the treatment course, OR are receiving voriconazole for the secondary prophylaxis against IFI during or after chemotherapy
- Agree to give one additional blood sample twice during the study for the purposes of pharmacogenetic analysis and determination of the serum trough voriconazole concentration, whilst their blood is being collected during normal clinical follow up without the requirement for any additional intravenous intervention
- Are willing and able to give informed consent and sign the informed consent form
You may not qualify if:
- Have previously had CYP2C19 PGx testing performed
- Pregnant/breastfeeding
- Have cognitive impairment and/or psychiatric disorders and/or any other condition that will draw into question their capacity to provide informed consent
- Have severe hepatic insufficiency (Child-Pugh Class C) and have renal failure (estimated GFR \<15ml/min /1,73m2)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Dokuz Eylul Universitylead
- University of Liverpoolcollaborator
Study Sites (1)
Dokuz Eylul University Hospital
Izmir, 35340, Turkey (Türkiye)
Biospecimen
9 mL of blood sample collected into an EDTA (Ethylenediaminetetraacetic Acid) tube for PGx analysis 9 mL of blood sample collected into an EDTA (Ethylenediaminetetraacetic Acid) tube for voriconazole TDM
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Mukaddes Gumustekin, Professor, MD, PhD
Dokuz Eylul University
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- COHORT
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Full Professor
Study Record Dates
First Submitted
September 7, 2020
First Posted
September 14, 2020
Study Start
November 1, 2019
Primary Completion
December 31, 2021
Study Completion
October 31, 2022
Last Updated
September 16, 2020
Record last verified: 2020-09