A Trial Comparing Efficacy and Safety of Voriconazole Administered With Therapeutic Drug Monitoring vs. Standard Dosing
Condition: Fungal Infection
MeSH terms: Mycoses
Intervention: Prospective TDM Arm
Intervention description: Voriconazole dose will be adjusted based on per protocol obtained TDM levels
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: All
Minimum age: 12 Years
Maximum age: 100 Years
Healthy volunteers: No
Keywords: Voriconazole; Therapeutic drug monitoring; Hematopoietic stem cell transplant; Hematologic malignancy; Invasive mould infection

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.
    

Eligibility criteria:

        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.