PharmacologyNCT00359541
Voriconazole Blood Levels and Toxicity
An observational study of Pharmacology, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
This study will look at how voriconazole, a drug used to treat or protect against fungal infections, affects the body. Adverse effects associated with voriconazole include skin problems and temporary changes in vision, mental status and liver function. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Pharmacology
- How many people
- 98 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Jan 2006to 25 Jun 2010
- 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 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients, at least 12 years old with no restriction of gender, race or disabilities, followed by the National Institute of Allergy and Infectious Diseases (NIAID), National Cancer Institute (NCI) and National Heart Lung and Blood Institute (NHLBI) who begin treatment with voriconazole either oral or intravenous.
- Patients who have a previous voriconazole course at least 7 days before current course.
Who cannot join
- Time elapsed greater than 15 days from initiation of voriconazole treatment for inpatients and greater than 30 days from initiation of voriconazole treatment for outpatients.
- Patients who the medical staffs caring for the patient not want entered into the study.
- Patients unable to give informed consent, due to the severity of their medical condition (Comatose patients, ICU patients under sedation).
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Voriconazole Plasma Concentration and Toxicity
This study will look at how voriconazole, a drug used to treat or protect against fungal infections, affects the body. Adverse effects associated with voriconazole include skin problems and temporary changes in vision, mental status and liver function. There is some evidence that these side effects may be more intense when there are high levels of the drug in the blood. The amount of voriconazole in the body is determined by how much of the drug the patient receives and by the patient's ability to inactivate and excrete it, which may be determined in part by genes. This study will examine: 1) side effects patients develop from voriconazole; 2) whether the side effects experienced are related to the concentration of drug in the body; and 3) the role of genes in determining how quickly the body inactivates and excretes the drug.
Patients 12 and older who are participating in studies in the National Institute of Allergy and Infectious Diseases (NIAID), the National Cancer Institute (NCI) or the National Heart, Lung, and Blood Institute (NHLBI) and have been treated with voriconazole for 15 days or less may be eligible for this study.
Read more
Participation involves the following:
- Identification and recording of adverse effects patients experience due to voriconazole treatment
- Collection of basic information about the patient's medical history and treatment
- Blood draws once a week during the patient's hospitalization
- Collection of routine laboratory test results ordered by the patient's doctor
- Blood draw to identify genes responsible for voriconazole inactivation
- Weekly monitoring for the possibility of voriconazole adverse effects
- Blood draw to measure blood levels of voriconazole when the drug is stopped, if it is stopped because of an adverse effect
- Evaluations at outpatient visits, including a blood draw to measure voriconazole blood levels
Participation in the study ends 7 days after voriconazole treatment is stopped because it is no longer needed.
Read the detailed description
Voriconazole (Vfend(Registered Trademark), Pfizer) has achieved common usage at the NIH (National Institutes of Health) Clinical Research Center for the treatment of fungal infections in immunosuppressed patients. Toxicity includes relatively frequent but reversible changes in vision and more infrequent, potentially serious hepatotoxicity, decreased cognitive function and rash. Incidence of these more serious adverse events has been difficult to ascertain because of the morbidity of underlying disease in patients receiving voriconazole, but a minimum estimate is 10 percent. It is known that voriconazole plasma concentrations vary between patients over a fifty-fold range but it is not known whether toxicity is related to plasma drug exposure. The reason for the differing voriconazole plasma concentrations between normal individuals is partly due to genetic variations in hepatic cytochrome enzymes CYP2C9 and CYP2C19 (Cytochrome P450, family 2, subfamily C, polypeptide 9 and 19, respectively). In patients with underlying illness, drug interactions and decreased hepatic drug clearance may contribute to variability.
The purpose of the study is to record prospectively the adverse effects of voriconazole in Clinical Center patients who have been prescribed the drug by their primary physician. We will ask the primary physician to order a trough voriconazole plasma levels once a week. The test will not be reported to the physician. Because interpretation of the test is unknown, the physicians will be blinded to the report. Rather, the primary objective of the study is to analyze the voriconazole plasma concentrations when the study is completed to determine if there is a concentration and duration of drug exposure that correlates with toxicity. A secondary objective is to determine the 2C9 and 2C19 genotype of patients and search for possible correlations between genotype and plasma voriconazole concentrations. Administration of other drugs given to the patient will be tracked to analyze whether any previously unknown drug interactions seem to have changed the voriconazole plasma concentration. The study will also determine the incidence of adverse effects of voriconazole in our patient population.
- Conditions
- Pharmacology
- Keywords
- CYP2C9, CYP2C19, Pharmacology, Genotype, Metabolism
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2006 (estimated)
- Study start19 Jan 2006
- Study completion25 Jun 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for PharmacologyStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The 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
- Enrolment
- 98 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00359541
- Sponsor's protocol ID
- 060077
- Other IDs
- 06-I-0077
- Status last verified
- 25 Jun 2010
- First submitted
- 1 Aug 2006
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Jantunen E, Ruutu P, Niskanen L, Volin L, Parkkali T, Koukila-Kahkola P, Ruutu T. Incidence and risk factors for invasive fungal infections in allogeneic BMT recipients. Bone Marrow Transplant. 1997 Apr;19(8):801-8. doi: 10.1038/sj.bmt.1700737.
PubMed 9134172Herbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann JW, Kern WV, Marr KA, Ribaud P, Lortholary O, Sylvester R, Rubin RH, Wingard JR, Stark P, Durand C, Caillot D, Thiel E, Chandrasekar PH, Hodges MR, Schlamm HT, Troke PF, de Pauw B; Invasive Fungal Infections Group of the European Organisation for Research and Treatment of Cancer and the Global Aspergillus Study Group. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med. 2002 Aug 8;347(6):408-15. doi: 10.1056/NEJMoa020191.
PubMed 12167683Walsh TJ, Pappas P, Winston DJ, Lazarus HM, Petersen F, Raffalli J, Yanovich S, Stiff P, Greenberg R, Donowitz G, Schuster M, Reboli A, Wingard J, Arndt C, Reinhardt J, Hadley S, Finberg R, Laverdiere M, Perfect J, Garber G, Fioritoni G, Anaissie E, Lee J; National Institute of Allergy and Infectious Diseases Mycoses Study Group. Voriconazole compared with liposomal amphotericin B for empirical antifungal therapy in patients with neutropenia and persistent fever. N Engl J Med. 2002 Jan 24;346(4):225-34. doi: 10.1056/NEJM200201243460403.
PubMed 11807146
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Voriconazole Plasma Concentration and Toxicity
- ClinicalTrials.gov ID
- NCT00359541
- Acronym / sponsor ID
- 060077
- Conditions
- Pharmacology
- Keywords
- CYP2C9, CYP2C19, Pharmacology, Genotype, Metabolism
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 98 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 19 Jan 2006
- Study completion
- 25 Jun 2010
- First posted
- 2 Aug 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.
This study will look at how voriconazole, a drug used to treat or protect against fungal infections, affects the body. Adverse effects associated with voriconazole include skin problems and temporary changes in vision, mental status and liver function. There is some evidence that these side effects may be more intense when there are high levels of the drug in the blood. The amount of voriconazole in the body is determined by how much of the drug the patient receives and by the patient's ability to inactivate and excrete it, which may be determined in part by genes. This study will examine: 1) side effects patients develop from voriconazole; 2) whether the side effects experienced are related to the concentration of drug in the body; and 3) the role of genes in determining how quickly the body inactivates and excretes the drug.
Patients 12 and older who are participating in studies in the National Institute of Allergy and Infectious Diseases (NIAID), the National Cancer Institute (NCI) or the National Heart, Lung, and Blood Institute (NHLBI) and have been treated with voriconazole for 15 days or less may be eligible for this study.
Participation involves the following:
- Identification and recording of adverse effects patients experience due to voriconazole treatment
- Collection of basic information about the patient's medical history and treatment
- Blood draws once a week during the patient's hospitalization
- Collection of routine laboratory test results ordered by the patient's doctor
- Blood draw to identify genes responsible for voriconazole inactivation
- Weekly monitoring for the possibility of voriconazole adverse effects
- Blood draw to measure blood levels of voriconazole when the drug is stopped, if it is stopped because of an adverse effect
- Evaluations at outpatient visits, including a blood draw to measure voriconazole blood levels
Participation in the study ends 7 days after voriconazole treatment is stopped because it is no longer needed.
Detailed description
Voriconazole (Vfend(Registered Trademark), Pfizer) has achieved common usage at the NIH (National Institutes of Health) Clinical Research Center for the treatment of fungal infections in immunosuppressed patients. Toxicity includes relatively frequent but reversible changes in vision and more infrequent, potentially serious hepatotoxicity, decreased cognitive function and rash. Incidence of these more serious adverse events has been difficult to ascertain because of the morbidity of underlying disease in patients receiving voriconazole, but a minimum estimate is 10 percent. It is known that voriconazole plasma concentrations vary between patients over a fifty-fold range but it is not known whether toxicity is related to plasma drug exposure. The reason for the differing voriconazole plasma concentrations between normal individuals is partly due to genetic variations in hepatic cytochrome enzymes CYP2C9 and CYP2C19 (Cytochrome P450, family 2, subfamily C, polypeptide 9 and 19, respectively). In patients with underlying illness, drug interactions and decreased hepatic drug clearance may contribute to variability.
The purpose of the study is to record prospectively the adverse effects of voriconazole in Clinical Center patients who have been prescribed the drug by their primary physician. We will ask the primary physician to order a trough voriconazole plasma levels once a week. The test will not be reported to the physician. Because interpretation of the test is unknown, the physicians will be blinded to the report. Rather, the primary objective of the study is to analyze the voriconazole plasma concentrations when the study is completed to determine if there is a concentration and duration of drug exposure that correlates with toxicity. A secondary objective is to determine the 2C9 and 2C19 genotype of patients and search for possible correlations between genotype and plasma voriconazole concentrations. Administration of other drugs given to the patient will be tracked to analyze whether any previously unknown drug interactions seem to have changed the voriconazole plasma concentration. The study will also determine the incidence of adverse effects of voriconazole in our patient population.
Study design
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- Patients, at least 12 years old with no restriction of gender, race or disabilities, followed by the National Institute of Allergy and Infectious Diseases (NIAID), National Cancer Institute (NCI) and National Heart Lung and Blood Institute (NHLBI) who begin treatment with voriconazole either oral or intravenous.
- Patients who have a previous voriconazole course at least 7 days before current course.
Key exclusion criteria (3 listed)
- Time elapsed greater than 15 days from initiation of voriconazole treatment for inpatients and greater than 30 days from initiation of voriconazole treatment for outpatients.
- Patients who the medical staffs caring for the patient not want entered into the study.
- Patients unable to give informed consent, due to the severity of their medical condition (Comatose patients, ICU patients under sedation).
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 9134172Jantunen E, Ruutu P, Niskanen L, Volin L, Parkkali T, Koukila-Kahkola P, Ruutu T. Incidence and risk factors for invasive fungal infections in allogeneic BMT recipients. Bone Marrow Transplant. 1997 Apr;19(8):801-8. doi: 10.1038/sj.bmt.1700737.
- Background: PubMed 12167683Herbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann JW, Kern WV, Marr KA, Ribaud P, Lortholary O, Sylvester R, Rubin RH, Wingard JR, Stark P, Durand C, Caillot D, Thiel E, Chandrasekar PH, Hodges MR, Schlamm HT, Troke PF, de Pauw B; Invasive Fungal Infections Group of the European Organisation for Research and Treatment of Cancer and the Global Aspergillus Study Group. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med. 2002 Aug 8;347(6):408-15. doi: 10.1056/NEJMoa020191.
- Background: PubMed 11807146Walsh TJ, Pappas P, Winston DJ, Lazarus HM, Petersen F, Raffalli J, Yanovich S, Stiff P, Greenberg R, Donowitz G, Schuster M, Reboli A, Wingard J, Arndt C, Reinhardt J, Hadley S, Finberg R, Laverdiere M, Perfect J, Garber G, Fioritoni G, Anaissie E, Lee J; National Institute of Allergy and Infectious Diseases Mycoses Study Group. Voriconazole compared with liposomal amphotericin B for empirical antifungal therapy in patients with neutropenia and persistent fever. N Engl J Med. 2002 Jan 24;346(4):225-34. doi: 10.1056/NEJM200201243460403.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Pharmacology, run by National Institute of Allergy and Infectious Diseases (NIAID) 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 2 inclusion and 3 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: finished, as of the sponsor's last update on 2 Jul 2017. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
On the ClinicalTrials.gov record for NCT00359541, which also lists 3 linked publications.
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 2 Jul 2017.