- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00893555
Pharmacologic Optimization of Voriconazole (VORI911)
Pharmacologic Optimization of Voriconazole - a Prospective Clustered Group-randomized Cross-over Trial of Therapeutic Drug Monitoring
Study Overview
Status
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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-
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Groningen, Netherlands, 9713GZ
- University Medical Center Groningen
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- allergic to voriconazole or its excipients
- age below 18 years
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: control
Voriconazole dosing based on SPC
|
No serum concentrations are determined
Other Names:
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Experimental: TDM
Voriconazole serum concentration based dosing
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TDM (through level of 2-5mg/L).
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
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28 days
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Overall mortality
Time Frame: 7 and 28 days; 12 weeks
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7 and 28 days; 12 weeks
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% of serum concentrations within 2-5mg/L
Time Frame: 7 and 28 days; 12 weeks
|
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
|
7 and 28 days; 12 weeks
|
Side effects
Time Frame: 7 and 28 days; 12 weeks
|
7 and 28 days; 12 weeks
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Time to global response
Time Frame: 7 and 28 days; 12 weeks
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7 and 28 days; 12 weeks
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Cost-effectiveness of TDM
Time Frame: 7 and 28 days; 12 weeks
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7 and 28 days; 12 weeks
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Chair: J GW Kosterink, PharmD, PhD, University Medical Center Groningen
- Principal Investigator: J WC Alffenaar, PharmD PhD, University Medical Center Groningen
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Infections
- Neoplasms by Site
- Hematologic Diseases
- Bacterial Infections and Mycoses
- Neoplasms
- Hematologic Neoplasms
- Mycoses
- Invasive Fungal Infections
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 Enzyme Inhibitors
- Hormone Antagonists
- Antifungal Agents
- Steroid Synthesis Inhibitors
- 14-alpha Demethylase Inhibitors
- Voriconazole
Other Study ID Numbers
- VORI911
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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