Pharmacologic Optimization of Voriconazole (VORI911)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by University Medical Centre Groningen
Sponsor:
Collaborators:
University Medical Center Nijmegen
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
VU University Medical Center
Leiden University Medical Center
UMC Utrecht
Erasmus Medical Center
Maastricht University Medical Center
Isala Klinieken
Alysis Zorggroep
St. Antonius Hospital
Meander Medical Center
Haga Hospital, Leyweg
Information provided by (Responsible Party):
JWC Alffenaar, University Medical Centre Groningen
ClinicalTrials.gov Identifier:
NCT00893555
First received: May 4, 2009
Last updated: November 12, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Invasive Fungal Infection
Hematological Malignancy
Drug: voriconazole
Drug: voriconazole (dosing according to the SPC)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pharmacologic Optimization of Voriconazole - a Prospective Clustered Group-randomized Cross-over Trial of Therapeutic Drug Monitoring

Resource links provided by NLM:


Further study details as provided by University Medical Centre Groningen:

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. [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Overall mortality [ Time Frame: 7 and 28 days; 12 weeks ] [ Designated as safety issue: Yes ]
  • % of serum concentrations within 2-5mg/L [ Time Frame: 7 and 28 days; 12 weeks ] [ Designated as safety issue: Yes ]
  • % switched to salvage therapy or measured concentration level in control arm [ Time Frame: 7 and 28 days; 12 weeks ] [ Designated as safety issue: Yes ]
  • Side effects [ Time Frame: 7 and 28 days; 12 weeks ] [ Designated as safety issue: Yes ]
  • Time to global response [ Time Frame: 7 and 28 days; 12 weeks ] [ Designated as safety issue: No ]
  • Cost-effectiveness of TDM [ Time Frame: 7 and 28 days; 12 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 200
Study Start Date: April 2009
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: control
Voriconazole dosing based on SPC
Drug: voriconazole (dosing according to the SPC)
No serum concentrations are determined
Other Name: Vfend
Experimental: TDM
Voriconazole serum concentration based dosing
Drug: voriconazole
TDM (through level of 2-5mg/L).
Other Name: Vfend

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00893555

Locations
Netherlands
University Medical Center Groningen Recruiting
Groningen, Netherlands, 9713GZ
Contact: J WC Alffenaar, PharmD    +31-50-3616161      
Principal Investigator: S MG Daenen, MD PhD         
Sponsors and Collaborators
JWC Alffenaar
University Medical Center Nijmegen
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
VU University Medical Center
Leiden University Medical Center
UMC Utrecht
Erasmus Medical Center
Maastricht University Medical Center
Isala Klinieken
Alysis Zorggroep
St. Antonius Hospital
Meander Medical Center
Haga Hospital, Leyweg
Investigators
Study Chair: J GW Kosterink, PharmD, PhD University Medical Centre Groningen
Principal Investigator: J WC Alffenaar, PharmD PhD University Medical Centre Groningen
  More Information

No publications provided

Responsible Party: JWC Alffenaar, PhD PharmD, University Medical Centre Groningen
ClinicalTrials.gov Identifier: NCT00893555     History of Changes
Other Study ID Numbers: VORI911
Study First Received: May 4, 2009
Last Updated: November 12, 2013
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by University Medical Centre Groningen:
Invasive fungal infection
hematological malignancy
voriconazole
therapeutic drug monitoring

Additional relevant MeSH terms:
Neoplasms
Mycoses
Hematologic Neoplasms
Neoplasms by Site
Hematologic Diseases
Voriconazole
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 22, 2014