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

NCT01416025 | Completed Phase 4 Results

• 1 other identifier: NA_00041916
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

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.

Conditions

Fungal Infection

Keywords

Voriconazole; Therapeutic drug monitoring; Hematopoietic stem cell transplant; Hematologic malignancy; Invasive mould infection

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment Failure

  The primary endpoint of the study will be a binary outcome, called Failure, defined as one of the following: measured at 42 days from initiation of drug administration: 1. Progression of underlying infection (clinical failure) 2. Death 3. Development of a voriconazole-associated SAE: LFTs, Rash, Visual disturbance, Neurologic abnormality (e.g: hallucinations)

  42 days

Study Arms (2)

Prospective TDM Arm

EXPERIMENTAL

Voriconazole dose will be adjusted based on per protocol obtained TDM levels

Drug: Prospective TDM Arm

Standard dosing

NO INTERVENTION

Standard doses of voriconazole will be used

Interventions

Prospective TDM Arm DRUG

Voriconazole dose will be adjusted based on per protocol obtained TDM levels

Also known as: VFEND

Prospective TDM Arm

Eligibility Criteria

• Age: 12 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Johns Hopkins University: lead
• Pfizer: collaborator

Study Sites (1)

Johns Hopkins

Baltimore, Maryland, 21205, United States

Location

MeSH Terms

Conditions

Mycoses; Hematologic Neoplasms

Interventions

Voriconazole

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections; Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Darin Ostrander
• Organization: JohnHopkinsU

dostrander@jhu.edu

(443) 287-6217

Study Officials

• Kieren Marr, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine and Oncology

Study Record Dates

• First Submitted: August 11, 2011
• First Posted: August 12, 2011
• Study Start: January 1, 2012
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: August 18, 2016
• Results First Posted: May 23, 2016

Record last verified: 2016-07

Locations

US (1)