Aspergillosis
Conditions
Keywords
invasive aspergillosis, opportunistic mold infection
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.
Interventions
DRUGvoriconazole
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).
DRUGanidulafungin
Loading dose of 200 mg QD followed by maintenance dose of 100 mg QD for up to a total of 28 days therapy
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Summary of Global Response at End of Treatment (EOT) | End of Treatment (Day 42) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Summary of Global Response at Week 2, Week 4, and Week 6 | Week 2, Week 4, 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. |
| Summary of Mortality | Up to Week 6 | Number of subects with documented mortality (death). |
| Galactomannan Titer Assay Levels and Global Response | Up to Week 6 | 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. |
| Voriconazole Trough Levels With Intravenous and Oral Dosing | Week 1 through Week 6 | Voriconazole trough plasma concentrations measured as nanograms per milliliter (ng/mL). |
Countries
United States
Participant flow
Pre-assignment details
Study was closed due to an overall low rate of enrollment after only 6 subjects enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Anidulalfungin and Voriconazole Voriconazole: subjects with creatinine clearance at least 50 milliliters per minute (ml/min) will receive initial treatment with intravenous (IV) (loading dose of 6 milligrams per kilogram \[mg/kg\] every 12 hours \[Q12h\]) followed by maintenance dose of 4 mg/kg Q12h or oral (PO) (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).
Anidulafungin: loading dose of 200 mg once daily (QD) followed by maintenance dose of 100 mg QD for up to a total of 28 days therapy.
Subjects remain on combination therapy for minimum of 14 days and a maximum of 28 days; after combination therapy complete, subjects may remain on a maintenance dose of Voriconazole monotherapy until Day 42. | 6 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Anidulalfungin and Voriconazole |
|---|---|
| Age, Customized Between 57 and 83 years | 6 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 6 / 6 |
| serious Total, serious adverse events | 4 / 6 |
Outcome results
Primary
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.
Time frame: End of Treatment (Day 42)
Population: Intent-to-treat (ITT): includes all subjects who received at least 1 dose of study medication. No descriptive or inferential analysis was completed due to low enrollment and subsequent early termination of study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anidulalfungin and Voriconazole | Summary of Global Response at End of Treatment (EOT) | Failure (No response) | 1 participants |
| Anidulalfungin and Voriconazole | Summary of Global Response at End of Treatment (EOT) | Partial response | 3 participants |
| Anidulalfungin and Voriconazole | Summary of Global Response at End of Treatment (EOT) | Stable response | 0 participants |
| Anidulalfungin and Voriconazole | Summary of Global Response at End of Treatment (EOT) | Complete response | 2 participants |
Secondary
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.
Time frame: Up to Week 6
Population: ITT. No descriptive or inferential analysis was completed due to low enrollment and subsequent early termination of study.
Secondary
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.
Time frame: Week 2, Week 4, Week 6
Population: ITT; due to low study enrollment, data not summarized by global response at Week 2, Week 4, and Week 6. Cross-reference outcome measure: Summary of Global Response at End of Treatment (EOT).
Secondary
Summary of Mortality
Number of subects with documented mortality (death).
Time frame: Up to Week 6
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anidulalfungin and Voriconazole | Summary of Mortality | 1 participants |
Secondary
Voriconazole Trough Levels With Intravenous and Oral Dosing
Voriconazole trough plasma concentrations measured as nanograms per milliliter (ng/mL).
Time frame: Week 1 through Week 6
Population: ITT; only 1 pharmacokinetic sample was collected for each subject, therefore a comprehensive analysis of trough plasma concentrations was not completed due to insufficient data.