Pharmacologic Optimization of Voriconazole

Hematological Malignancy Clinical Trial

— VORI911  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00893555
• Other study ID #: VORI911
• Status: Completed
• Phase: Phase 3
• First received: May 4, 2009
• Last updated: January 11, 2017
• Start date: April 2009
• Est. completion date: January 2017

Study information

• Verified date: January 2017
• Source: University Medical Center Groningen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 189
• Est. completion date: January 2017
• Est. primary completion date: November 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hematological Malignancy
• Invasive Fungal Infection
• Mycoses
• Neoplasms

Intervention

Drug:
• voriconazole
TDM (through level of 2-5mg/L).
• voriconazole (dosing according to the SPC)
No serum concentrations are determined

Locations

Country	Name	City	State
Netherlands	University Medical Center Groningen	Groningen

Sponsors (11)

Lead Sponsor	Collaborator
Jan-Willem C Alffenaar	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Erasmus Medical Center, Haga Hospital, Leyweg, Klinikum Oldenburg gGmbH, Leiden University Medical Center, Meander Medical Center, St. Antonius Hospital, UMC Utrecht, University Medical Center Nijmegen, VU University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		28 days	Yes
Secondary	Overall mortality		7 and 28 days; 12 weeks	Yes
Secondary	% of serum concentrations within 2-5mg/L		7 and 28 days; 12 weeks	Yes
Secondary	% switched to salvage therapy or measured concentration level in control arm		7 and 28 days; 12 weeks	Yes
Secondary	Side effects		7 and 28 days; 12 weeks	Yes
Secondary	Time to global response		7 and 28 days; 12 weeks	No
Secondary	Cost-effectiveness of TDM		7 and 28 days; 12 weeks	Yes