Liver TransplantNCT00371605
An Assessment of Voriconazole Pharmacokinetics and Pharmacogenetics in Liver Transplant Recipients - Pilot Study
An observational study of Liver Transplant and Fungal Infection, run by University of Pittsburgh at 1 site in United States.
Trial summary
A fixed-dosing regimen of voriconazole is routinely used as prophylaxis against aspergillosis in liver transplant patients admitted to the transplant intensive care unit at UPMC. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Transplant, Fungal Infection
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2006to Apr 2007
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: liver transplant patients getting voriconazole clinically
Who may be able to join
- Consecutive male or female liver transplant recipients, 18 years old, who are initiated on the voriconazole prophylactic regimen by their transplant physician as part of their standard care, will be eligible for inclusion in the study.
Who cannot join
- Transplant recipients receiving voriconazole to treat an active fungal infection will be excluded. Transplant recipients that are concurrently receiving medications that are documented to affect voriconazole pharmacokinetics will be excluded. The agents included, but may not be limited to the following; carbamazepine, phenytoin, omeprazole, rifabutin, rifampin, ketoconazole, itraconazole, fluconazole, St. John's wort extract. Those who require therapy with protease inhibitors for human immunodeficiency virus (HIV) infection may be included in the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
About this study
A fixed-dosing regimen of voriconazole is routinely used as prophylaxis against aspergillosis in liver transplant patients admitted to the transplant intensive care unit at UPMC. We hypothesize that use of a fixed-dosing regimen of voriconazole will lead to a large degree of variability in drug exposure among liver transplant patients due to: 1) variability in absorption and elimination caused by physiological characteristics unique to this patient population 2) its non-linear pharmacokinetics and 3) the potential for polymorphism in the genes that encode for cytochrome P-450 enzymes that metabolize voriconazole. This is a pilot clinical pharmacokinetic evaluation that will: 1) characterize the plasma concentration versus time profile of voriconazole in liver transplant patients receiving a fixed-dosing regimen to assess for extremes in systemic exposure 2) determine the oral bioavailability of voriconazole in liver transplant patients 3) assess for functionally significant allelic variation of the cytochrome P-450 enzymes that metabolize voriconazole (CYP2C9, CYP2C19 and CYP3A4/5) in both recipient blood and allograft tissue that may contribute extremes in systemic exposure among liver transplant patients. This evaluation will allow for an assessment of the adequacy of the prophylactic regimen in achieving therapeutic drug concentrations in all subjects. Additionally, the utility of genotyping as a clinical tool to identify patients at risk for extremes in voriconazole exposure will be evaluated. The characterization of the pharmacokinetics in liver transplant patients may be utilized to define an optimal therapeutic regimen that will be individualized to target specific concentrations to maximize efficacy and minimize side-effects.
Read the detailed description
All liver transplant patients receiving voriconazole prophylaxis are eligible to participate in this study. We propose a single-center, observational study in 15 liver transplant patients who are admitted to the ICU and receiving voriconazole prophylaxis as part of standard care. Each patient will undergo blood sampling (27 mL) on one occasion (Pharmacokinetic Study I), while receiving oral voriconazole. A small portion of blood (1 mL) collected during this blood sampling period will be retained for genotyping (specific aim III).
Voriconazole prophylaxis is most often administered to liver transplant patients via the oral route (200 mg twice daily). However, circumstances may arise necessitating the administration of intravenous doses of voriconazole for a subset of patients, as part of their standard care. . Thus, these patients will undergo blood sampling on a maximum two additional occasions: 1) surrounding an intravenous dose dose (27 mL) 2) surrounding an oral dose (27 mL) .
The amount of voriconazole present in the blood samples will be measured via high pressure liquid chromatography. Individual plasma concentration time profiles will be determined following oral and intravenous dosing, respectively. Pharmacokinetic parameter estimates will be derived via population and individual pharmacokinetic data analysis.
The use, dose, and frequency of the medication voriconazole is up to the clinical staff. We will not be altering the delivery, dose or use of the drug. Therefore we cannot provide you with the requested information because it will all depend on the clinical team. We are not intervening to enroll subjects. Subjects will only be enrolled if they are placed on voriconazole and they agreed to participate.
- Conditions
- Liver Transplant, Fungal Infection
- Keywords
- Voriconazole, Liver Transplant, Fungal Infection
- Medical subject headings
- Mycoses
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2006 (estimated)
- Study startDec 2006
- Study completionApr 2007
Why it stopped: Enrolled requested number of patients and completed study. In analysis
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver TransplantStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Time perspective
- Prospective
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Investigators
- Blair Capitano, Pharm D, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00371605
- Sponsor's protocol ID
- IRB# 0607030
- Status last verified
- Dec 2007
- First submitted
- 31 Aug 2006
- Last updated
- 17 Dec 2007
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2007. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Assessment of Voriconazole Pharmacokinetics and Pharmacogenetics in Liver Transplant Recipients - Pilot Study
- ClinicalTrials.gov ID
- NCT00371605
- Acronym / sponsor ID
- IRB# 0607030
- Conditions
- Liver Transplant, Fungal Infection
- Keywords
- Voriconazole, Liver Transplant, Fungal Infection
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Enrolled requested number of patients and completed study. In analysis
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Study start
- Dec 2006
- Study completion
- Apr 2007 (actual)
- First posted
- 4 Sep 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A fixed-dosing regimen of voriconazole is routinely used as prophylaxis against aspergillosis in liver transplant patients admitted to the transplant intensive care unit at UPMC. We hypothesize that use of a fixed-dosing regimen of voriconazole will lead to a large degree of variability in drug exposure among liver transplant patients due to: 1) variability in absorption and elimination caused by physiological characteristics unique to this patient population 2) its non-linear pharmacokinetics and 3) the potential for polymorphism in the genes that encode for cytochrome P-450 enzymes that metabolize voriconazole. This is a pilot clinical pharmacokinetic evaluation that will: 1) characterize the plasma concentration versus time profile of voriconazole in liver transplant patients receiving a fixed-dosing regimen to assess for extremes in systemic exposure 2) determine the oral bioavailability of voriconazole in liver transplant patients 3) assess for functionally significant allelic variation of the cytochrome P-450 enzymes that metabolize voriconazole (CYP2C9, CYP2C19 and CYP3A4/5) in both recipient blood and allograft tissue that may contribute extremes in systemic exposure among liver transplant patients. This evaluation will allow for an assessment of the adequacy of the prophylactic regimen in achieving therapeutic drug concentrations in all subjects. Additionally, the utility of genotyping as a clinical tool to identify patients at risk for extremes in voriconazole exposure will be evaluated. The characterization of the pharmacokinetics in liver transplant patients may be utilized to define an optimal therapeutic regimen that will be individualized to target specific concentrations to maximize efficacy and minimize side-effects.
Detailed description
All liver transplant patients receiving voriconazole prophylaxis are eligible to participate in this study. We propose a single-center, observational study in 15 liver transplant patients who are admitted to the ICU and receiving voriconazole prophylaxis as part of standard care. Each patient will undergo blood sampling (27 mL) on one occasion (Pharmacokinetic Study I), while receiving oral voriconazole. A small portion of blood (1 mL) collected during this blood sampling period will be retained for genotyping (specific aim III).
Voriconazole prophylaxis is most often administered to liver transplant patients via the oral route (200 mg twice daily). However, circumstances may arise necessitating the administration of intravenous doses of voriconazole for a subset of patients, as part of their standard care. . Thus, these patients will undergo blood sampling on a maximum two additional occasions: 1) surrounding an intravenous dose dose (27 mL) 2) surrounding an oral dose (27 mL) .
The amount of voriconazole present in the blood samples will be measured via high pressure liquid chromatography. Individual plasma concentration time profiles will be determined following oral and intravenous dosing, respectively. Pharmacokinetic parameter estimates will be derived via population and individual pharmacokinetic data analysis.
The use, dose, and frequency of the medication voriconazole is up to the clinical staff. We will not be altering the delivery, dose or use of the drug. Therefore we cannot provide you with the requested information because it will all depend on the clinical team. We are not intervening to enroll subjects. Subjects will only be enrolled if they are placed on voriconazole and they agreed to participate.
Study design
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- liver transplant patients getting voriconazole clinically
Key inclusion criteria (1 listed)
- Consecutive male or female liver transplant recipients, 18 years old, who are initiated on the voriconazole prophylactic regimen by their transplant physician as part of their standard care, will be eligible for inclusion in the study.
Key exclusion criteria (1 listed)
- Transplant recipients receiving voriconazole to treat an active fungal infection will be excluded. Transplant recipients that are concurrently receiving medications that are documented to affect voriconazole pharmacokinetics will be excluded. The agents included, but may not be limited to the following; carbamazepine, phenytoin, omeprazole, rifabutin, rifampin, ketoconazole, itraconazole, fluconazole, St. John's wort extract. Those who require therapy with protease inhibitors for human immunodeficiency virus (HIV) infection may be included in the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study was stopped early (reason given: Enrolled requested number of patients and completed study. In analysis). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2007.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Blair Capitano, Pharm D principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Liver Transplant and Fungal Infection, run by University of Pittsburgh at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 Dec 2007. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Enrolled requested number of patients and completed study. In analysis). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2007.