Aspergillosis InvasivePhase 4VORIPRECINCT06582186
Individualized First Maintenance Doses of Voriconazole Through a Multiparametric Algorithm
A Phase 4 study testing Individualization of first voriconazole maintenance doses in people with Aspergillosis Invasive and Fungal Infection, run by University Hospital, Grenoble at 1 site in France.
Trial summary
The goal of this interventional single-arm study is to evaluate the interest of a multiparametric algorithm for individualization of first voriconazole maintenance doses for improvement of initial voriconazole exposure in adult patients with haematological malignancies. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Aspergillosis Invasive, Fungal Infection, Hematologic Malignancy
- What is being tested?
- Individualization of first voriconazole maintenance doses
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteFrance
- Study dates
- Oct 2024to Oct 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
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
Who may be able to join
- adult patient suffering from haematological malignancy
- followed in the clinical hematology department or in the hematology day hospital of the Grenoble Alps University Hospital
- consenting to carrying out CYP2C19 genotyping
- likely to start treatment with voriconazole (for curative or prophylactic purposes as part of care)
- having signed a written consent to participate
- affiliated to a social security system
Who cannot join
- comedication with strong inhibitors/inducers (valproic acid, phenytoin, carbamazepine, rifampicin)
- Subject during exclusion period from another study,
- Persons referred to in articles L1121-5 to L1121-8 of the CSP (corresponds to all protected persons: pregnant woman, parturient woman, breastfeeding mother, person deprived of liberty by judicial or administrative decision, persons subject to care psychiatric pursuant to articles L. 3212-1 and L. 3213-1 who do not fall under the provisions of article L. 1121-8, persons admitted to a health or social establishment for purposes other than research , minors, person subject to a legal protection measure or unable to express their consent)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Thiebaut-bertrand Anne, MD contact
About this study
Official title: Individualization of First Maintenance Doses of Voriconazole Using a Multiparametric Algorithm in Hematology Patients: a Prospective Single-arm Interventional Study
The goal of this interventional single-arm study is to evaluate the interest of a multiparametric algorithm for individualization of first voriconazole maintenance doses for improvement of initial voriconazole exposure in adult patients with haematological malignancies. The main objective it aims is to determine the percentage of patients with initial voriconazole trough concentrations in the therapeutic range after individualization of first maintenance doses.
Participants will benefited from individualization of first voriconazole maintenance doses through a previously developed and validated multiparametric algorithm (publication in progress) taking into account CYP2C19 genotype, C reactive protein level and age.
Read the detailed description
The currently recommended therapeutic drug monitoring of voriconazole has improved the efficacy of this treatment and reduced its adverse effects, especially for treatment and prophylaxis of invasive aspergillosis. However, dose adjustments made as part of this therapeutic drug monitoring only occur at the earliest 3 to 5 days after the initiation of treatment, whereas it is essential to achieve effective concentrations from the start of treatment. Simple a priori dose adjustment approaches based on CYP2C19 genotype have been shown to improve voriconazole exposure and treatment response. However other factors such as the patient\'s inflammatory status or age also influence voriconazole exposure, suggesting that strategies for individualizing initial voriconazole doses could be improved by integrating all covariates influencing voriconazole pharmacokinetics. In this line, a previous multicenter and international study has developped and validated an algorithm for calculating the first maintenance doses integrating not only the CYP2C19 genotype, but also the inflammatory status, the patient\'s age, and the presence (or not) of hematological malignancy. Here, the investigators propose to evaluate the interest of this multiparametric algorithm for improving initial exposure (within the first 4 days) to voriconazole in patients suffering from haematological malignancies.
- Being tested
- Individualization of first voriconazole maintenance doses
- Keywords
- model-informed precision dosing, single-arm prospective interventional study, Simon design
- Medical subject headings
- Mycoses, Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Individualization of first voriconazole maintenance dosesDrug
Individualization of first voriconazole maintenance doses
| Study group | Role | What they receive |
|---|---|---|
| individualized maintenance doses | Experimental | Individualization of first maintenance doses through a multiparametric algorithm integrating CYP2C19 genotype, C reactive protein level and age Receives: Drug: Individualization of first voriconazole maintenance doses |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of patients with initial plasma voriconazole trough concentration in the therapeutic range
Measured: Day 5 +/-2
Secondary outcomes (7)
Frequency of initial plasma voriconazole trough concentrations above the therapeutic range
Measured: Day 5 +/-2
Frequency of initial plasma voriconazole trough concentrations below the therapeutic range
Measured: Day 5 +/-2
Voriconazole area under the curve (AUC0-12h) after the first maintenance dose individualized
Measured: Day 2
Time to get the therapeutic range
Measured: through study completion, an average of 3 months
Treatment outcome in patients curatively treated
Measured: At month 3 +/- 15 days
Frequency of side effects
Measured: through study completion, an average of 3 months
Percentage of patients with initial plasma voriconazole trough concentration in the therapeutic range
comparison with an historic cohort
Measured: Day 5 +/-2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2024
- Study startOct 2024 (estimated)
- Primary completionOct 2027 (estimated)
- Study completionOct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Aspergillosis InvasiveStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Grenoble
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Gautier-Veyret Elodie, Principal investigator, Grenoble Alps University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06582186
- Sponsor's protocol ID
- 38RC23.0230
- Other IDs
- 2024-A01425-42
- Acronym
- VORIPRECI
- Status last verified
- Aug 2024
- First submitted
- 22 Aug 2024
- Last updated
- 3 Sep 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Gautier-Veyret E, Thiebaut-Bertrand A, Roustit M, Bolcato L, Depeisses J, Schacherer M, Schummer G, Fonrose X, Stanke-Labesque F. Optimization of voriconazole therapy for treatment of invasive aspergillosis: Pharmacogenomics and inflammatory status need to be evaluated. Br J Clin Pharmacol. 2021 Jun;87(6):2534-2541. doi: 10.1111/bcp.14661. Epub 2020 Dec 13.
PubMed 33217017Bolcato L, Khouri C, Veringa A, Alffenaar JWC, Yamada T, Naito T, Lamoureux F, Fonrose X, Stanke-Labesque F, Gautier-Veyret E. Combined Impact of Inflammation and Pharmacogenomic Variants on Voriconazole Trough Concentrations: A Meta-Analysis of Individual Data. J Clin Med. 2021 May 13;10(10):2089. doi: 10.3390/jcm10102089.
PubMed 34068031
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Individualization of First Maintenance Doses of Voriconazole Using a Multiparametric Algorithm in Hematology Patients: a Prospective Single-arm Interventional Study
- ClinicalTrials.gov ID
- NCT06582186
- Acronym / sponsor ID
- VORIPRECI / 38RC23.0230
- Keywords
- model-informed precision dosing, single-arm prospective interventional study, Simon design
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- University Hospital, GrenobleUniversity, hospital or other
- Study start
- Oct 2024 (estimated)
- Primary completion
- Oct 2027 (estimated)
- Study completion
- Oct 2027 (estimated)
- First posted
- 3 Sep 2024 (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.
The goal of this interventional single-arm study is to evaluate the interest of a multiparametric algorithm for individualization of first voriconazole maintenance doses for improvement of initial voriconazole exposure in adult patients with haematological malignancies. The main objective it aims is to determine the percentage of patients with initial voriconazole trough concentrations in the therapeutic range after individualization of first maintenance doses.
Participants will benefited from individualization of first voriconazole maintenance doses through a previously developed and validated multiparametric algorithm (publication in progress) taking into account CYP2C19 genotype, C reactive protein level and age.
Detailed description
The currently recommended therapeutic drug monitoring of voriconazole has improved the efficacy of this treatment and reduced its adverse effects, especially for treatment and prophylaxis of invasive aspergillosis. However, dose adjustments made as part of this therapeutic drug monitoring only occur at the earliest 3 to 5 days after the initiation of treatment, whereas it is essential to achieve effective concentrations from the start of treatment. Simple a priori dose adjustment approaches based on CYP2C19 genotype have been shown to improve voriconazole exposure and treatment response. However other factors such as the patient\'s inflammatory status or age also influence voriconazole exposure, suggesting that strategies for individualizing initial voriconazole doses could be improved by integrating all covariates influencing voriconazole pharmacokinetics. In this line, a previous multicenter and international study has developped and validated an algorithm for calculating the first maintenance doses integrating not only the CYP2C19 genotype, but also the inflammatory status, the patient\'s age, and the presence (or not) of hematological malignancy. Here, the investigators propose to evaluate the interest of this multiparametric algorithm for improving initial exposure (within the first 4 days) to voriconazole in patients suffering from haematological malignancies.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| individualized maintenance doses | Experimental | Drug: Individualization of first voriconazole maintenance dosesIndividualization of first maintenance doses through a multiparametric algorithm integrating CYP2C19 genotype, C reactive protein level and age |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- adult patient suffering from haematological malignancy
- followed in the clinical hematology department or in the hematology day hospital of the Grenoble Alps University Hospital
- consenting to carrying out CYP2C19 genotyping
- likely to start treatment with voriconazole (for curative or prophylactic purposes as part of care)
- having signed a written consent to participate
Key exclusion criteria (3 listed)
- comedication with strong inhibitors/inducers (valproic acid, phenytoin, carbamazepine, rifampicin)
- Subject during exclusion period from another study,
- Persons referred to in articles L1121-5 to L1121-8 of the CSP (corresponds to all protected persons: pregnant woman, parturient woman, breastfeeding mother, person deprived of liberty by judicial or administrative decision, persons subject to care psychiatric pursuant to articles L. 3212-1 and L. 3213-1 who do not fall under the provisions of article L. 1121-8, persons admitted to a health or social establishment for purposes other than research , minors, person subject to a legal protection measure or unable to express their consent)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Individualization of first voriconazole maintenance dosesIndividualization of first voriconazole maintenance doses | Drug | individualized maintenance doses |
Primary outcome
Percentage of patients with initial plasma voriconazole trough concentration in the therapeutic range
Time frame: Day 5 +/-2
7 secondary outcomes
Frequency of initial plasma voriconazole trough concentrations above the therapeutic range
Time frame: Day 5 +/-2
Frequency of initial plasma voriconazole trough concentrations below the therapeutic range
Time frame: Day 5 +/-2
Voriconazole area under the curve (AUC0-12h) after the first maintenance dose individualized
Time frame: Day 2
Time to get the therapeutic range
Time frame: through study completion, an average of 3 months
Treatment outcome in patients curatively treated
Time frame: At month 3 +/- 15 days
Frequency of side effects
Time frame: through study completion, an average of 3 months
Percentage of patients with initial plasma voriconazole trough concentration in the therapeutic range
Time frame: Day 5 +/-2
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2024.
- Background: PubMed 33217017Gautier-Veyret E, Thiebaut-Bertrand A, Roustit M, Bolcato L, Depeisses J, Schacherer M, Schummer G, Fonrose X, Stanke-Labesque F. Optimization of voriconazole therapy for treatment of invasive aspergillosis: Pharmacogenomics and inflammatory status need to be evaluated. Br J Clin Pharmacol. 2021 Jun;87(6):2534-2541. doi: 10.1111/bcp.14661. Epub 2020 Dec 13.
- Background: PubMed 34068031Bolcato L, Khouri C, Veringa A, Alffenaar JWC, Yamada T, Naito T, Lamoureux F, Fonrose X, Stanke-Labesque F, Gautier-Veyret E. Combined Impact of Inflammation and Pharmacogenomic Variants on Voriconazole Trough Concentrations: A Meta-Analysis of Individual Data. J Clin Med. 2021 May 13;10(10):2089. doi: 10.3390/jcm10102089.
- 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.
Thiebaut-bertrand Anne, MD contact
Gautier-Veyret Elodie principal investigator
Grenoble Alps University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Individualization of first voriconazole maintenance doses in people with Aspergillosis Invasive and Fungal Infection, 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 6 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: opening soon, as of the sponsor's last update on 3 Sep 2024. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Gautier-Veyret Elodie, PharmD, PhD (+33476765492, Egautier@chu-grenoble.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of patients with initial plasma voriconazole trough concentration in the therapeutic range (time frame: Day 5 +/-2). 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 NCT06582186, which also lists 2 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 3 Sep 2024; AzTrials last refreshed its copy on 30 Oct 2026.