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Completed

NCT Number: NCT00893555

Pharmacologic Optimization of Voriconazole

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.

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Key information

Conditions

Invasive Fungal Infection Bacterial Infections and Mycoses Hematologic Diseases Hematologic Neoplasms Hematological Malignancy Hemic and Lymphatic Diseases Infections Invasive Fungal Infections Mycoses Neoplasms Neoplasms by Site

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

University Medical Center Groningen

Groningen, Provincie Groningen, 9713GZ, Netherlands

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Voriconazole

Drug

TDM (through level of 2-5mg/L).

Other names: Vfend

voriconazole (dosing according to the SPC)

Drug

No serum concentrations are determined

Other names: Vfend

Primary outcomes

  1. 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 outcomes

  1. Overall mortality

    Time frame: 7 and 28 days; 12 weeks

  2. % of serum concentrations within 2-5mg/L

    Time frame: 7 and 28 days; 12 weeks

  3. % switched to salvage therapy or measured concentration level in control arm

    Time frame: 7 and 28 days; 12 weeks

  4. Side effects

    Time frame: 7 and 28 days; 12 weeks

  5. Time to global response

    Time frame: 7 and 28 days; 12 weeks

  6. Cost-effectiveness of TDM

    Time frame: 7 and 28 days; 12 weeks

Sponsors and collaborators

Lead sponsor

Jan-Willem C Alffenaar

Other

Collaborators

  • Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
  • Amsterdam UMC, location VUmc
  • Erasmus Medical Center
  • Haga Hospital
  • Klinikum Oldenburg gGmbH
  • Leiden University Medical Center
  • Meander Medical Center
  • St. Antonius Hospital
  • UMC Utrecht
  • University Medical Center Nijmegen

Registry information

Official study title

Pharmacologic Optimization of Voriconazole - a Prospective Clustered Group-randomized Cross-over Trial of Therapeutic Drug Monitoring

Acronym: VORI911

Important dates

Study start
2009
Primary completion
2016
Study completion
2017
First posted
May 6, 2009
Registry last updated
Jan 12, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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