| Exclusion Criteria: | 1) Known history of allergy, hypersensitivity or serious reaction to azole or echinocandin antifungals;
2) Female patients who are pregnant or lactating;
3) Patients with sarcoidosis, aspergilloma, or allergic bronchopulmonary aspergillosis (ABPA);
4) Patients with chronic invasive aspergillosis with a duration of symptoms or radiological finding for more than 4 weeks prior to study entry;
5) Patients who are receiving and cannot discontinue the following drugs at least 24 hours prior to randomization: terfenadine, astemizole, cisapride, pimozide or quinidine (because of the possibility of QT prolongation);
6) Patients receiving any of the following medications: sirolimus, rifampin, rifabutin, carbamazepine, long-acting barbiturates (eg, phenobarbital, mephobarbital), ritonavir, efavirenz, or ergot alkaloids (eg, ergotamine, dihydroergotamine);
7) There are other potentially clinically relevant interactions between voriconazole and some commonly prescribed drugs. While these drugs have not been contraindicated, advice on monitoring or dosage adjustments is made in the protocol.
8) Receipt of systemic antifungal treatment for the current episode of invasive aspergillosis fora duration of greater than 96 hours. NOTE: Patients receiving mold active prophylaxis may be enrolled provided that they meet criteria for proven or probable IA at the time of enrollment.
9) Severe liver dysfunction (defined as total bilirubin >10x upper limit of normal, or AST, ALT, or alkaline phosphatase >5x upper limit of normal). Local laboratory results may be used to qualify individuals for enrollment. However, if laboratory values drawn at the Baseline visit exceed the above limits for exclusion, the medical monitor must be contacted without delay to discuss continuation of study treatment;
10) Patients on artificial ventilation;
11) 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;
12) Patients who are receiving, or are likely to receive, any Phase I investigational drug. Patients receiving Phase II or Phase III investigational drugs may be enrolled only with the prior approval of the medical monitor. Patients receiving investigational drugs that are currently licensed for other indications may be enrolled;
13) The inclusion of a patient more than once in this trial is not permissible;
14) Patients not expected to survive for at least 5 days or who have a Karnofsky score of less than or equal to 20 ;
15) Patients with a high likelihood of death due to factors unrelated to aspergillosis (eg, due to relapsed malignancy, severe graft versus host disease, other underlying diseases, etc.) within 30 days following planned enrollment (investigator's discretion);
16) Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study;
17) Concomitant administration of systemic agents active against Aspergillus species is not permissible. |