A Trial Comparing Efficacy and Safety of Voriconazole Administered With Therapeutic Drug Monitoring vs. Standard Dosing

NCT01416025

Last updated date
Study Location
Johns Hopkins
Baltimore, Maryland, 21205, United States
Contact
1-800-718-1021

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Fungal Infection
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
12-100 years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- Indication for voriconazole administration: proven, probable, or possible IMI, excluding zygomycosis (based on the revised EORTC/MSG consensus definitions) [De Pauw, Clin Infect Dis. 2008; 46:1813].

- Male or female ≥12 years of age.

- Evidence of a personally signed and dated informed consent document in accordance with local regulatory and legal requirements indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study.

- Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- Known history of allergy, hypersensitivity or serious reaction to azole antifungals.


- Patients with aspergilloma or allergic bronchopulmonary aspergillosis (ABPA).


- Patients with chronic invasive aspergillosis with duration of symptoms or radiological
finding for more than 4 weeks prior to study entry.


- Patients who are receiving and cannot discontinue the following drugs at least 24
hours prior to randomization: terfenadine, pimozide or quinidine (because of the
possibility of QT prolongation), St John's wort preparation.


- Patients receiving any of the following medications: sirolimus, rifampin, rifabutin,
carbamazepine, long acting barbiturates (e.g., phenobarbital, mephobarbital),
ritonavir, efavirenz, or ergot alkaloids (e.g., ergotamine, dihydroergotamine).


- Receipt of more than 5 days of voriconazole as treatment prior to enrollment.


- Receipt of 7 days or more of systemic antifungal treatment for the current episode of
IMI.


- Severe liver dysfunction (defined as total bilirubin, AST, ALT, or alkaline
phosphatase >5x upper limit of normal). Local laboratory results may be used to
qualify individuals for enrollment.


- Patients with any condition which, in the opinion of the investigator, could affect
patient safety, preclude evaluation of response, or make it unlikely that the proposed
course of therapy can be completed.


- Patients who have already participated in this trial within the last 30 days.


- Patients with a high likelihood of death due to factors unrelated to IA (e.g., due to
relapsed malignancy, severe GVHD, other underlying diseases, etc.) within 30 days
following planned enrollment (investigator's discretion).


- Patients that weigh <45 and >120 kg, respectively, upon enrollment. If patients'
weight is beyond those limits upon serial assessments during the study period, the
study monitor should be contacted and decisions to keep or withdraw subject from the
study will be made.

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Fungal InfectionA Trial Comparing Efficacy and Safety of Voriconazole Administered With Therapeutic Drug Monitoring vs. Standard Dosing
NCT01416025
  1. Baltimore, Maryland
ALL GENDERS
12 Years+
years
MULTIPLE SITES
Fungal InfectionVfend Special Investigation For Prophylaxis
NCT02674685
ALL GENDERS
0+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE A Trial Comparing Efficacy and Safety of Voriconazole Administered With Therapeutic Drug Monitoring vs. Standard Dosing
Official Title  ICMJE A Prospective, Randomized Trial Comparing the Efficacy and Safety of Voriconazole Administered With Therapeutic Drug Monitoring vs. Standard Dosing
Brief Summary This is a prospective, multicenter, randomized trial to study therapeutic drug monitoring (TDM) of voriconazole among patients with an invasive mould infection (IMI). The primary objective of this study will be to assess the effect of prospective voriconazole TDM on the composite of adverse events (AE) and clinical response.
Detailed Description

This is a prospective study of patients who receive voriconazole as treatment for an IMI (proven, probable, and possible by the EORTC/MSG definitions), other than zygomycosis. Patients will be randomized to receive either standard dosing or dosing based on TDM, stratified by whether initial voriconazole therapy is PO or IV. Assessment of outcomes will be made 42 days after start of voriconazole. An additional follow up for safety reporting will be performed 4weeks after completion of voriconazole

The patients will be randomized to:

  • Prospective TDM: voriconazole dose will be adjusted based on per protocol obtained TDM levels, and
  • Standard dosing: standard doses of voriconazole will be used.

In the prospective TDM arm, voriconazole TDM will be performed in real time at each site and results will be reported to treating physicians for dose adjustment. All efforts will be taken to obtain results within 24 hours of blood sample collection. In the standard dosing arm, blood samples will be collected, stored, and batched for voriconazole levels to be tested retrospectively. Voriconazole plasma levels will be measured by validated high performance liquid chromatography (HPLC) assays as detailed. Voriconazole trough levels will be performed on Day Baseline/Screening, 5, 14, 28, and 42.

Voriconazole peak level will be measured on Day 5. Trough voriconazole levels will be obtained in case of an event, defined as suspected drug-associated toxicity and/or clinical failure.

Assessment of AEs for all patients will be monitored during the study and response to treatment will be assessed. The composite of overall AE/clinical failure will be assessed on day 42.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Fungal Infection
Intervention  ICMJE Drug: Prospective TDM Arm
Voriconazole dose will be adjusted based on per protocol obtained TDM levels
Other Name: VFEND
Study Arms  ICMJE
  • Experimental: Prospective TDM Arm
    Voriconazole dose will be adjusted based on per protocol obtained TDM levels
    Intervention: Drug: Prospective TDM Arm
  • No Intervention: Standard dosing
    Standard doses of voriconazole will be used
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 19, 2015)
29
Original Estimated Enrollment  ICMJE
 (submitted: August 11, 2011)
146
Actual Study Completion Date  ICMJE December 2014
Actual Primary Completion Date December 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Indication for voriconazole administration: proven, probable, or possible IMI, excluding zygomycosis (based on the revised EORTC/MSG consensus definitions) [De Pauw, Clin Infect Dis. 2008; 46:1813].
  • Male or female ?12 years of age.
  • Evidence of a personally signed and dated informed consent document in accordance with local regulatory and legal requirements indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study.
  • Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria:

  • Known history of allergy, hypersensitivity or serious reaction to azole antifungals.
  • Patients with aspergilloma or allergic bronchopulmonary aspergillosis (ABPA).
  • Patients with chronic invasive aspergillosis with duration of symptoms or radiological finding for more than 4 weeks prior to study entry.
  • Patients who are receiving and cannot discontinue the following drugs at least 24 hours prior to randomization: terfenadine, pimozide or quinidine (because of the possibility of QT prolongation), St John's wort preparation.
  • Patients receiving any of the following medications: sirolimus, rifampin, rifabutin, carbamazepine, long acting barbiturates (e.g., phenobarbital, mephobarbital), ritonavir, efavirenz, or ergot alkaloids (e.g., ergotamine, dihydroergotamine).
  • Receipt of more than 5 days of voriconazole as treatment prior to enrollment.
  • Receipt of 7 days or more of systemic antifungal treatment for the current episode of IMI.
  • Severe liver dysfunction (defined as total bilirubin, AST, ALT, or alkaline phosphatase >5x upper limit of normal). Local laboratory results may be used to qualify individuals for enrollment.
  • Patients with any condition which, in the opinion of the investigator, could affect patient safety, preclude evaluation of response, or make it unlikely that the proposed course of therapy can be completed.
  • Patients who have already participated in this trial within the last 30 days.
  • Patients with a high likelihood of death due to factors unrelated to IA (e.g., due to relapsed malignancy, severe GVHD, other underlying diseases, etc.) within 30 days following planned enrollment (investigator's discretion).
  • Patients that weigh <45 and >120 kg, respectively, upon enrollment. If patients' weight is beyond those limits upon serial assessments during the study period, the study monitor should be contacted and decisions to keep or withdraw subject from the study will be made.
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 12 Years to 100 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries Canada
 
Administrative Information
NCT Number  ICMJE NCT01416025
Other Study ID Numbers  ICMJE NA_00041916
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Kieren Marr, Johns Hopkins University
Study Sponsor  ICMJE Johns Hopkins University
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Principal Investigator:Kieren Marr, MDJohns Hopkins University
PRS Account Johns Hopkins University
Verification Date July 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP