Invasive AspergillosisVORIGENENCT03067350
Influence of a Combined Pharmacogenetic Score on Through Plasma Voriconazole Concentrations in Haematological Patients
An observational study of Invasive Aspergillosis and Haematological Cancer Patients, run by University Hospital, Grenoble at 1 site in France.
Trial summary
Hypothesis: A pharmacogenetic score integrating both CYP3A genotypes could be influence initial trough voriconazole plasma concentrations and thus useful to adapt a priori voriconazole dosing in order to get adequate voriconazole exposure as possible after starting treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Invasive Aspergillosis, Haematological Cancer Patients, Voriconazole
- How many people
- 47 participants
- Where
- 1 siteFrance
- Study dates
- Jan 2015to Jan 2019
- 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: patients suffering from haematological cancer Followed at the hematolofic clinic of Grenoble University Hospital Starting treatment by voriconazole whatever the route of administration
Who may be able to join
- patients suffering from haematological cancer
Who cannot join
- less than 18-years old
Trial locations and contacts
1 site in 1 country.
About this study
Hypothesis: A pharmacogenetic score integrating both CYP3A genotypes could be influence initial trough voriconazole plasma concentrations and thus useful to adapt a priori voriconazole dosing in order to get adequate voriconazole exposure as possible after starting treatment.
Main Objective: To determine predictive value of a combined pharmacogenetic score on onset of trough voriconazole plasma concentration inferior than lower therapeutic target.
Read the detailed description
Voriconazole (VRC), the gold-standard treatment of invasive aspergillosis is characterized by variables and nonlinear pharmacokinetics, causing many under- or over-dosing. A link exist between trough plasma concentrations (Cmin) of VRC and effectiveness but also its toxicity. Thus the longitudinal therapeutic drug monitoring of VRC is now recommended with a therapeutic range between 1 and 5 mg/L. The pharmacokinetic variability of VRC is in part explained by its metabolism, mainly dependent on cytochrome P 450 (CYP), particularly CYP2C19, 3A4, 3A5; all these CYP exhibiting genetic polymorphisms. The authors, recently shown, and for the first time , in a retrospective study conducted in 29 patients allogeneic hematopoietic stem cell that initial VRC Cmin adjusted the dose was not only influenced by the route of administration but also by a pharmacogenetics score whose determination is to assign each genotype CYP2C19 and CYP3A a score expressed in a arbitrary units.
The combined pharmacogenetic score was strongly correlated with the original Cmin (r= -0.748; p = 0.002) and was the only independent predictor of initial Cmin (after adjusting the dose and the route of administration). In addition, none of the patients having a genetic score <2 (ie metabolizing capacity of reduced VRC) did not show an initial Cmin below 1 mg/L, while the initial Cmin was below this threshold efficiency in 47% of patients with a genetic score >2. The aim of this new study is to confirm the impact of the pharmacogenetic score on the initial VRC Cmin over a larger prospective cohort of 60 adult patients with onco-hematological diseases.
- Keywords
- voriconazole, pharmacogenetics, pharmacokinetics, therapeutic drug monitoring
What is being measured
The primary outcome is the main question the study is designed to answer.
number of initial voriconazole trough plasma concentration in the therapeutic range (1-4mg/l)
Initial voriconazole trough plasma concentration
Measured: concentration measured between 5 to 10 days after voriconazole treatment initiation
Secondary outcomes (3)
initial voriconazole trough plasma concentrations adjusted on the dose
Initial voriconazole trough plasma concentration
Measured: concentration measured between 5 to 10 days after voriconazole treatment initiation
number of patients with therapeutic success
treatment outcome determined 3 months after voriconazole initiation (failure, stable response, success)
Measured: 3 months after voriconazole therapy initiation
number of patients with adverse effects
adverse effects include neurological disorders such as visual disturbance and/or hallucinations and hepatotoxicity (evaluated by ALAT/ASAT, bilirubin and γ-GT levels),
Measured: duration of voriconazole treatment (maximum length of follow-up : 3 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2017
- Study startJan 2015
- Primary completionJan 2019
- Study completionJan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Invasive AspergillosisStudies of the same condition, open and under way.
- More trials run by University Hospital, GrenobleThe 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
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Grenoble
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Elodie GAUTIER, Principal investigator, University Hospital, Grenoble
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03067350
- Sponsor's protocol ID
- 38RC15.168
- Acronym
- VORIGENE
- Status last verified
- Feb 2019
- First submitted
- 6 Feb 2017
- Last updated
- 18 Feb 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Gautier-Veyret E, Fonrose X, Tonini J, Thiebaut-Bertrand A, Bartoli M, Quesada JL, Bulabois CE, Cahn JY, Stanke-Labesque F. Variability of voriconazole plasma concentrations after allogeneic hematopoietic stem cell transplantation: impact of cytochrome p450 polymorphisms and comedications on initial and subsequent trough levels. Antimicrob Agents Chemother. 2015 Apr;59(4):2305-14. doi: 10.1128/AAC.04838-14. Epub 2015 Feb 2.
PubMed 25645831Gautier-Veyret E, Fonrose X, Stanke-Labesque F. A genetic score combining CYP450 2C19 and 3A4 genotypes to predict voriconazole plasma exposure? Int J Antimicrob Agents. 2016 Aug;48(2):221-2. doi: 10.1016/j.ijantimicag.2016.05.002. Epub 2016 Jun 7. No abstract available.
PubMed 27318623Tonini J, Bailly S, Gautier-Veyret E, Wambergue C, Pelloux H, Thiebaut-Bertrand A, Cornet M, Stanke-Labesque F, Maubon D. Contribution of a Simple Bioassay in Effective Therapeutic Drug Monitoring of Posaconazole and Voriconazole. Ther Drug Monit. 2015 Oct;37(5):685-8. doi: 10.1097/FTD.0000000000000199.
PubMed 26384041Tonini J, Thiebaut A, Jourdil JF, Berruyer AS, Bulabois CE, Cahn JY, Stanke-Labesque F. Therapeutic drug monitoring of posaconazole in allogeneic hematopoietic stem cell transplantation patients who develop gastrointestinal graft-versus-host disease. Antimicrob Agents Chemother. 2012 Oct;56(10):5247-52. doi: 10.1128/AAC.00815-12. Epub 2012 Jul 30.
PubMed 22850515Jourdil JF, Tonini J, Stanke-Labesque F. Simultaneous quantitation of azole antifungals, antibiotics, imatinib, and raltegravir in human plasma by two-dimensional high-performance liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2013 Mar 1;919-920:1-9. doi: 10.1016/j.jchromb.2012.12.028. Epub 2013 Jan 9.
PubMed 23384531
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Influence of a Combined Pharmacogenetic Score on Through Plasma Voriconazole Concentrations in Haematological Patients
- ClinicalTrials.gov ID
- NCT03067350
- Acronym / sponsor ID
- VORIGENE / 38RC15.168
- Keywords
- voriconazole, pharmacogenetics, pharmacokinetics, therapeutic drug monitoring
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- University Hospital, GrenobleUniversity, hospital or other
- Study start
- Jan 2015 (actual)
- Primary completion
- Jan 2019 (actual)
- Study completion
- Jan 2019 (actual)
- First posted
- 1 Mar 2017 (actual)
- 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.
Hypothesis: A pharmacogenetic score integrating both CYP3A genotypes could be influence initial trough voriconazole plasma concentrations and thus useful to adapt a priori voriconazole dosing in order to get adequate voriconazole exposure as possible after starting treatment.
Main Objective: To determine predictive value of a combined pharmacogenetic score on onset of trough voriconazole plasma concentration inferior than lower therapeutic target.
Detailed description
Voriconazole (VRC), the gold-standard treatment of invasive aspergillosis is characterized by variables and nonlinear pharmacokinetics, causing many under- or over-dosing. A link exist between trough plasma concentrations (Cmin) of VRC and effectiveness but also its toxicity. Thus the longitudinal therapeutic drug monitoring of VRC is now recommended with a therapeutic range between 1 and 5 mg/L. The pharmacokinetic variability of VRC is in part explained by its metabolism, mainly dependent on cytochrome P 450 (CYP), particularly CYP2C19, 3A4, 3A5; all these CYP exhibiting genetic polymorphisms. The authors, recently shown, and for the first time , in a retrospective study conducted in 29 patients allogeneic hematopoietic stem cell that initial VRC Cmin adjusted the dose was not only influenced by the route of administration but also by a pharmacogenetics score whose determination is to assign each genotype CYP2C19 and CYP3A a score expressed in a arbitrary units.
The combined pharmacogenetic score was strongly correlated with the original Cmin (r= -0.748; p = 0.002) and was the only independent predictor of initial Cmin (after adjusting the dose and the route of administration). In addition, none of the patients having a genetic score <2 (ie metabolizing capacity of reduced VRC) did not show an initial Cmin below 1 mg/L, while the initial Cmin was below this threshold efficiency in 47% of patients with a genetic score >2. The aim of this new study is to confirm the impact of the pharmacogenetic score on the initial VRC Cmin over a larger prospective cohort of 60 adult patients with onco-hematological diseases.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- patients suffering from haematological cancer Followed at the hematolofic clinic of Grenoble University Hospital Starting treatment by voriconazole whatever the route of administration
Key inclusion criteria (1 listed)
- patients suffering from haematological cancer
Key exclusion criteria (1 listed)
- less than 18-years old
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
number of initial voriconazole trough plasma concentration in the therapeutic range (1-4mg/l)
Time frame: concentration measured between 5 to 10 days after voriconazole treatment initiation
Initial voriconazole trough plasma concentration
3 secondary outcomes
initial voriconazole trough plasma concentrations adjusted on the dose
Time frame: concentration measured between 5 to 10 days after voriconazole treatment initiation
number of patients with therapeutic success
Time frame: 3 months after voriconazole therapy initiation
number of patients with adverse effects
Time frame: duration of voriconazole treatment (maximum length of follow-up : 3 months)
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 18 Feb 2019.
- Background: PubMed 25645831Gautier-Veyret E, Fonrose X, Tonini J, Thiebaut-Bertrand A, Bartoli M, Quesada JL, Bulabois CE, Cahn JY, Stanke-Labesque F. Variability of voriconazole plasma concentrations after allogeneic hematopoietic stem cell transplantation: impact of cytochrome p450 polymorphisms and comedications on initial and subsequent trough levels. Antimicrob Agents Chemother. 2015 Apr;59(4):2305-14. doi: 10.1128/AAC.04838-14. Epub 2015 Feb 2.
- Background: PubMed 27318623Gautier-Veyret E, Fonrose X, Stanke-Labesque F. A genetic score combining CYP450 2C19 and 3A4 genotypes to predict voriconazole plasma exposure? Int J Antimicrob Agents. 2016 Aug;48(2):221-2. doi: 10.1016/j.ijantimicag.2016.05.002. Epub 2016 Jun 7. No abstract available.
- Background: PubMed 26384041Tonini J, Bailly S, Gautier-Veyret E, Wambergue C, Pelloux H, Thiebaut-Bertrand A, Cornet M, Stanke-Labesque F, Maubon D. Contribution of a Simple Bioassay in Effective Therapeutic Drug Monitoring of Posaconazole and Voriconazole. Ther Drug Monit. 2015 Oct;37(5):685-8. doi: 10.1097/FTD.0000000000000199.
- Background: PubMed 22850515Tonini J, Thiebaut A, Jourdil JF, Berruyer AS, Bulabois CE, Cahn JY, Stanke-Labesque F. Therapeutic drug monitoring of posaconazole in allogeneic hematopoietic stem cell transplantation patients who develop gastrointestinal graft-versus-host disease. Antimicrob Agents Chemother. 2012 Oct;56(10):5247-52. doi: 10.1128/AAC.00815-12. Epub 2012 Jul 30.
- Background: PubMed 23384531Jourdil JF, Tonini J, Stanke-Labesque F. Simultaneous quantitation of azole antifungals, antibiotics, imatinib, and raltegravir in human plasma by two-dimensional high-performance liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2013 Mar 1;919-920:1-9. doi: 10.1016/j.jchromb.2012.12.028. Epub 2013 Jan 9.
- Individual participant dataSharing planned: No
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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.
Elodie GAUTIER principal investigator
University Hospital, Grenoble
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 Invasive Aspergillosis and Haematological Cancer Patients, run by University Hospital, Grenoble at 1 site in France.
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: finished, as of the sponsor's last update on 18 Feb 2019. 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 France. 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.
What does the primary outcome measure?
number of initial voriconazole trough plasma concentration in the therapeutic range (1-4mg/l) (time frame: concentration measured between 5 to 10 days after voriconazole treatment initiation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03067350, which also lists 5 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 18 Feb 2019; AzTrials last refreshed its copy on 7 Nov 2026.