Invasive Fungal InfectionPhase 3VORI911NCT00893555
Pharmacologic Optimization of Voriconazole
A Phase 3 study testing voriconazole and voriconazole (dosing according to the SPC) in people with Invasive Fungal Infection and Hematological Malignancy, run by Jan-Willem C Alffenaar at 1 site in Netherlands.
Trial summary
The objective of this study proposal is to determine whether pharmacologic optimization of voriconazole by means of therapeutic drug monitoring (TDM) results in improved patient outcomes (efficacy and safety) and is more cost-effective compared to the current standard of care. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Invasive Fungal Infection, Hematological Malignancy
- What is being tested?
- voriconazole and voriconazole (dosing according to the SPC)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 189 participants
- Where
- 1 siteNetherlands
- Study dates
- Apr 2009to Jan 2017
- Phase
- Phase 3
- 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
Who may be able to join
- are at least 18 years of age
- have received chemotherapy for haematological malignancies or have received a hematopoietic stem cell transplant
- proven, probable or possible invasive fungal disease according to the EORTC/MSG criteria
- treatment with voriconazole
Who cannot join
- allergic to voriconazole or its excipients
- age below 18 years
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
University Medical Center Groningen
Groningen, Provincie Groningen, 9713GZ
About this study
Official title: Pharmacologic Optimization of Voriconazole - a Prospective Clustered Group-randomized Cross-over Trial of Therapeutic Drug Monitoring
The objective of this study proposal is to determine whether pharmacologic optimization of voriconazole by means of therapeutic drug monitoring (TDM) results in improved patient outcomes (efficacy and safety) and is more cost-effective compared to the current standard of care.
Read the detailed description
Patients with haematological malignancies and chemotherapy-induced prolonged neutropenia are at risk for severe bacterial and fungal infections. These opportunistic infections can result in prolonged hospital stay, increases costs and greater mortality. Voriconazole has now been recommended as the first line agent for invasive pulmonary aspergillosis. Retrospective observational studies of voriconazole serum concentration suggest that serum concentration correlate with toxicity and clinical response. These observations were however made in small series of patients and data were collected retrospectively. These inherent methodological flaws make it impossible to draw definite conclusions about the effect of voriconazole serum level monitoring on the outcome of IA, and therefore considered insufficient proof to recommend voriconazole concentration determination in blood as standard of care. The impact that so called serum concentration guided dosing of voriconazole will have on treatment success can only be evaluated through a prospective randomized clinical trial.
For this purpose, we designed a prospective stratified cluster randomized cross-over trial of therapeutic drug monitoring in patients with haematological disease who have developed IA. The order of periods (TDM or standard of care, each 12 months) will be randomized per centre. During the TDM episode, the voriconazole dosage will be adjusted to achieve trough blood concentrations in a predefined window of 2-5 mg/L. A sample size of n=192 is needed to detect a 20% absolute reduction in the number of treatment failures (40% to 20 %) compared to control.
- Being tested
- voriconazole, voriconazole (dosing according to the SPC)
- Keywords
- Invasive fungal infection, hematological malignancy, voriconazole, therapeutic drug monitoring
- Medical subject headings
- Invasive Fungal Infections, Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
voriconazoleDrug
Also called Vfend
TDM (through level of 2-5mg/L).
voriconazole (dosing according to the SPC)Drug
Also called Vfend
No serum concentrations are determined
| Study group | Role | What they receive |
|---|---|---|
| control | Active comparator | Voriconazole dosing based on SPC Receives: Drug: voriconazole (dosing according to the SPC) |
| TDM | Experimental | Voriconazole serum concentration based dosing Receives: Drug: voriconazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary clinical endpoint will be a global response consisting of a combined endpoint of toxicity and response to therapy (clinical, microbiologic and radiologic responses) 28 days after starting treatment with voriconazole.
Measured: 28 days
Secondary outcomes (6)
Overall mortality
Measured: 7 and 28 days; 12 weeks
% of serum concentrations within 2-5mg/L
Measured: 7 and 28 days; 12 weeks
% switched to salvage therapy or measured concentration level in control arm
Measured: 7 and 28 days; 12 weeks
Side effects
Measured: 7 and 28 days; 12 weeks
Time to global response
Measured: 7 and 28 days; 12 weeks
Cost-effectiveness of TDM
Measured: 7 and 28 days; 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2009 (estimated)
- Study startApr 2009
- Primary completionNov 2016
- Study completionJan 2017
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 Invasive Fungal InfectionStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 189 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jan-Willem C Alffenaar
- Sponsor type
- University, hospital or other
- Collaborators
- University Medical Center Nijmegen, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Amsterdam UMC, location VUmc, Leiden University Medical Center, UMC Utrecht, Erasmus Medical Center, St. Antonius Hospital, Meander Medical Center, Haga Hospital, Klinikum Oldenburg gGmbH
- Responsible party
- Sponsor-investigator, Jan-Willem C Alffenaar, University Medical Center Groningen
- Investigators
- J GW Kosterink, PharmD, PhD, Study chair, University Medical Center GroningenJ WC Alffenaar, PharmD PhD, Principal investigator, University Medical Center Groningen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00893555
- Sponsor's protocol ID
- VORI911
- Acronym
- VORI911
- Status last verified
- Jan 2017
- First submitted
- 4 May 2009
- Last updated
- 12 Jan 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Klomp SD, Veringa A, Alffenaar JC, de Boer MGJ, Span LFR, Guchelaar HJ, Swen JJ. Inflammation altered correlation between CYP2C19 genotype and CYP2C19 activity in patients receiving voriconazole. Clin Transl Sci. 2024 Jul;17(7):e13887. doi: 10.1111/cts.13887.
PubMed 39010708Veringa A, Bruggemann RJ, Span LFR, Biemond BJ, de Boer MGJ, van den Heuvel ER, Klein SK, Kraemer D, Minnema MC, Prakken NHJ, Rijnders BJA, Swen JJ, Verweij PE, Wondergem MJ, Ypma PF, Blijlevens N, Kosterink JGW, van der Werf TS, Alffenaar JC; Voriconazole ZonMw Study Group. Therapeutic drug monitoring-guided treatment versus standard dosing of voriconazole for invasive aspergillosis in haematological patients: a multicentre, prospective, cluster randomised, crossover clinical trial. Int J Antimicrob Agents. 2023 Feb;61(2):106711. doi: 10.1016/j.ijantimicag.2023.106711. Epub 2023 Jan 13.
PubMed 36642232
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacologic Optimization of Voriconazole - a Prospective Clustered Group-randomized Cross-over Trial of Therapeutic Drug Monitoring
- ClinicalTrials.gov ID
- NCT00893555
- Acronym / sponsor ID
- VORI911 / VORI911
- Keywords
- Invasive fungal infection, hematological malignancy, voriconazole, therapeutic drug monitoring
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 189 participants (actual)
- Lead sponsor
- Jan-Willem C AlffenaarUniversity, hospital or other
- Collaborators
- University Medical Center Nijmegen, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Amsterdam UMC, location VUmc, Leiden University Medical Center, UMC Utrecht, Erasmus Medical Center, St. Antonius Hospital, Meander Medical Center, Haga Hospital, Klinikum Oldenburg gGmbH
- Study start
- Apr 2009
- Primary completion
- Nov 2016 (actual)
- Study completion
- Jan 2017 (actual)
- First posted
- 6 May 2009 (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.
The objective of this study proposal is to determine whether pharmacologic optimization of voriconazole by means of therapeutic drug monitoring (TDM) results in improved patient outcomes (efficacy and safety) and is more cost-effective compared to the current standard of care.
Detailed description
Patients with haematological malignancies and chemotherapy-induced prolonged neutropenia are at risk for severe bacterial and fungal infections. These opportunistic infections can result in prolonged hospital stay, increases costs and greater mortality. Voriconazole has now been recommended as the first line agent for invasive pulmonary aspergillosis. Retrospective observational studies of voriconazole serum concentration suggest that serum concentration correlate with toxicity and clinical response. These observations were however made in small series of patients and data were collected retrospectively. These inherent methodological flaws make it impossible to draw definite conclusions about the effect of voriconazole serum level monitoring on the outcome of IA, and therefore considered insufficient proof to recommend voriconazole concentration determination in blood as standard of care. The impact that so called serum concentration guided dosing of voriconazole will have on treatment success can only be evaluated through a prospective randomized clinical trial.
For this purpose, we designed a prospective stratified cluster randomized cross-over trial of therapeutic drug monitoring in patients with haematological disease who have developed IA. The order of periods (TDM or standard of care, each 12 months) will be randomized per centre. During the TDM episode, the voriconazole dosage will be adjusted to achieve trough blood concentrations in a predefined window of 2-5 mg/L. A sample size of n=192 is needed to detect a 20% absolute reduction in the number of treatment failures (40% to 20 %) compared to control.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| control | Active comparator | Drug: voriconazole (dosing according to the SPC)Voriconazole dosing based on SPC |
| TDM | Experimental | Drug: voriconazoleVoriconazole serum concentration based dosing |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- are at least 18 years of age
- have received chemotherapy for haematological malignancies or have received a hematopoietic stem cell transplant
- proven, probable or possible invasive fungal disease according to the EORTC/MSG criteria
- treatment with voriconazole
Key exclusion criteria (2 listed)
- allergic to voriconazole or its excipients
- age below 18 years
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 |
|---|---|---|
| voriconazoleAlso: VfendTDM (through level of 2-5mg/L). | Drug | TDM |
| voriconazole (dosing according to the SPC)Also: VfendNo serum concentrations are determined | Drug | control |
Primary outcome
The primary clinical endpoint will be a global response consisting of a combined endpoint of toxicity and response to therapy (clinical, microbiologic and radiologic responses) 28 days after starting treatment with voriconazole.
Time frame: 28 days
6 secondary outcomes
Overall mortality
Time frame: 7 and 28 days; 12 weeks
% of serum concentrations within 2-5mg/L
Time frame: 7 and 28 days; 12 weeks
% switched to salvage therapy or measured concentration level in control arm
Time frame: 7 and 28 days; 12 weeks
Side effects
Time frame: 7 and 28 days; 12 weeks
Time to global response
Time frame: 7 and 28 days; 12 weeks
Cost-effectiveness of TDM
Time frame: 7 and 28 days; 12 weeks
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 12 Jan 2017.
- Derived from this study: PubMed 39010708Klomp SD, Veringa A, Alffenaar JC, de Boer MGJ, Span LFR, Guchelaar HJ, Swen JJ. Inflammation altered correlation between CYP2C19 genotype and CYP2C19 activity in patients receiving voriconazole. Clin Transl Sci. 2024 Jul;17(7):e13887. doi: 10.1111/cts.13887.
- Derived from this study: PubMed 36642232Veringa A, Bruggemann RJ, Span LFR, Biemond BJ, de Boer MGJ, van den Heuvel ER, Klein SK, Kraemer D, Minnema MC, Prakken NHJ, Rijnders BJA, Swen JJ, Verweij PE, Wondergem MJ, Ypma PF, Blijlevens N, Kosterink JGW, van der Werf TS, Alffenaar JC; Voriconazole ZonMw Study Group. Therapeutic drug monitoring-guided treatment versus standard dosing of voriconazole for invasive aspergillosis in haematological patients: a multicentre, prospective, cluster randomised, crossover clinical trial. Int J Antimicrob Agents. 2023 Feb;61(2):106711. doi: 10.1016/j.ijantimicag.2023.106711. Epub 2023 Jan 13.
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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.
J GW Kosterink, PharmD, PhD study chair
University Medical Center Groningen
J WC Alffenaar, PharmD PhD principal investigator
University Medical Center Groningen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing voriconazole and voriconazole (dosing according to the SPC) in people with Invasive Fungal Infection and Hematological Malignancy, run by Jan-Willem C Alffenaar at 1 site in Netherlands.
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 4 inclusion and 2 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 12 Jan 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 Netherlands. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
The primary clinical endpoint will be a global response consisting of a combined endpoint of toxicity and response to therapy (clinical, microbiologic and radiologic responses) 28 days after starting treatment with voriconazole. (time frame: 28 days). 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 NCT00893555, 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 12 Jan 2017.