Study to Test the Combination of Voriconazole and Anidulafungin in Patients Who Have, or Are Thought to Have, Invasive Aspergillosis and Who Are Unable to Take a Common Antifungal Therapy (Polyene)

Study Overview
=================
Brief Summary
-----------------
This study will test the effectiveness and the safety of giving two antifungal agents (voriconazole and anidulafungin) together to treat invasive aspergillosis in patients who are unable to tolerate polyene therapy.

Detailed Description
-----------------
The study was terminated on January 12, 2009 due to the overall low rate of enrollment. The decision to terminate the trial was not based on any safety concerns. Patients who were enrolled in the study prior to January 12, 2009 were allowed to remain in the study until completing their participation as specified in the protocol.

Official Title
-----------------
Phase IV Open-Label Pilot Study to Evaluate the Combination of Voriconazole and Anidulafungin for the Treatment of Subjects With Proven or Probable Invasive Aspergillosis Who Are Intolerant of Polyene Treatment

Conditions
-----------------
Aspergillosis

Intervention / Treatment
-----------------
* Drug: voriconazole
* Drug: anidulafungin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Proven or probable invasive aspergillosis. Patient is intolerant to polyene therapy. Exclusion Criteria: Patients with invasive aspergillosis for more than 30 days at the time of study entry. Patients with uncontrolled bacterial or viral infection at the time of study entry. Patients with significant liver dysfunction or who are taking certain medications which interact with voriconazole.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: combination 2<br>anidulafungin plus voriconazole | Drug: voriconazole<br>* Subjects with creatinine clearance at least 50 ml/min will receive initial treatment with IV (loading dose of 6 mg/kg Q12h followed by maintenance dose of 4 mg/kg Q12h) or oral (loading dose of 400 mg Q12h followed by maintenance dose of 300 mg Q12h). Subjects with creatinine clearance <50 ml/min will receive oral voriconazole (loading dose of 400 mg Q12h followed by maintenance dose of 300 mg Q12h).<br>* Other names: Vfend;|
| Experimental: combination 1<br>anidulafungin plus voriconazole | Drug: anidulafungin<br>* Loading dose of 200 mg QD followed by maintenance dose of 100 mg QD for up to a total of 28 days therapy<br>* Other names: Eraxis;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Summary of Global Response at End of Treatment (EOT) | Number of subjects with global response consisting of a combination of clinical and radiological findings at the end of therapy. Possible outcome categories: Complete Response: resolution of all clinical signs and symptoms and more than 90% of lesions due to invasive aspergillosis that were visible on radiological studies; Partial Response: clinical improvement and greater than 50% improvement in radiological findings; Stable Response: no change from baseline or an improvement of less than 50% in radiological findings; Failure (no response): worsening disease. | End of Treatment (Day 42) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Summary of Global Response at Week 2, Week 4, and Week 6 | Number of subjects with global response consisting of a combination of clinical and radiological findings at the end of therapy. Possible outcome categories: Complete Response: resolution of all clinical signs and symptoms and more than 90% of lesions due to invasive aspergillosis that were visible on radiological studies; Partial Response: clinical improvement and greater than 50% improvement in radiological findings; Stable Response: no change from baseline or an improvement of less than 50% in radiological findings; Failure (no response): worsening disease. | Week 2, Week 4, Week 6 | 
| Summary of Mortality | Number of subects with documented mortality (death). | Up to Week 6 | 
| Galactomannan Titer Assay Levels and Global Response | Number of subjects per Galactomannan titer level with global response for all subjects (with or without renal impairment). The galactomann assay is an immunological blood serum test used to diagnose invasive aspergillosis and to monitor disease progression. Global response is a composite of clinical and radiological findings summarized as Complete Response: resolution of all clinical signs and symptoms; Partial Response: clinical improvement; Stable Response: no change from baseline or an improvement of less than 50% in radiological findings; Failure (no response): worsening disease. | Up to Week 6 | 
| Voriconazole Trough Levels With Intravenous and Oral Dosing | Voriconazole trough plasma concentrations measured as nanograms per milliliter (ng/mL). | Week 1 through Week 6 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
invasive aspergillosis, opportunistic mold infection