Pharmacologic Optimization of Voriconazole (VORI911)
Primary Purpose
Invasive Fungal Infection, Hematological Malignancy
Status
Completed
Phase
Phase 3
Locations
Netherlands
Study Type
Interventional
Intervention
voriconazole
voriconazole (dosing according to the SPC)
Sponsored by
About this trial
This is an interventional treatment trial for Invasive Fungal Infection focused on measuring Invasive fungal infection, hematological malignancy, voriconazole, therapeutic drug monitoring
Eligibility Criteria
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
Sites / Locations
- University Medical Center Groningen
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
control
TDM
Arm Description
Voriconazole dosing based on SPC
Voriconazole serum concentration based dosing
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Overall mortality
% of serum concentrations within 2-5mg/L
% switched to salvage therapy or measured concentration level in control arm
Side effects
Time to global response
Cost-effectiveness of TDM
Full Information
NCT ID
NCT00893555
First Posted
May 4, 2009
Last Updated
January 11, 2017
Sponsor
Jan-Willem C Alffenaar
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
1. Study Identification
Unique Protocol Identification Number
NCT00893555
Brief Title
Pharmacologic Optimization of Voriconazole
Acronym
VORI911
Official Title
Pharmacologic Optimization of Voriconazole - a Prospective Clustered Group-randomized Cross-over Trial of Therapeutic Drug Monitoring
Study Type
Interventional
2. Study Status
Record Verification Date
January 2017
Overall Recruitment Status
Completed
Study Start Date
April 2009 (undefined)
Primary Completion Date
November 2016 (Actual)
Study Completion Date
January 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Jan-Willem C Alffenaar
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
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Invasive Fungal Infection, Hematological Malignancy
Keywords
Invasive fungal infection, hematological malignancy, voriconazole, therapeutic drug monitoring
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
189 (Actual)
8. Arms, Groups, and Interventions
Arm Title
control
Arm Type
Active Comparator
Arm Description
Voriconazole dosing based on SPC
Arm Title
TDM
Arm Type
Experimental
Arm Description
Voriconazole serum concentration based dosing
Intervention Type
Drug
Intervention Name(s)
voriconazole
Other Intervention Name(s)
Vfend
Intervention Description
TDM (through level of 2-5mg/L).
Intervention Type
Drug
Intervention Name(s)
voriconazole (dosing according to the SPC)
Other Intervention Name(s)
Vfend
Intervention Description
No serum concentrations are determined
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
Overall mortality
Time Frame
7 and 28 days; 12 weeks
Title
% of serum concentrations within 2-5mg/L
Time Frame
7 and 28 days; 12 weeks
Title
% switched to salvage therapy or measured concentration level in control arm
Time Frame
7 and 28 days; 12 weeks
Title
Side effects
Time Frame
7 and 28 days; 12 weeks
Title
Time to global response
Time Frame
7 and 28 days; 12 weeks
Title
Cost-effectiveness of TDM
Time Frame
7 and 28 days; 12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
J GW Kosterink, PharmD, PhD
Organizational Affiliation
University Medical Center Groningen
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
J WC Alffenaar, PharmD PhD
Organizational Affiliation
University Medical Center Groningen
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Medical Center Groningen
City
Groningen
ZIP/Postal Code
9713GZ
Country
Netherlands
12. IPD Sharing Statement
Learn more about this trial
Pharmacologic Optimization of Voriconazole
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