Trial Outcomes & Findings for 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) (NCT NCT00620074)
NCT ID: NCT00620074
Last Updated: 2010-02-15
Results Overview
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.
TERMINATED
PHASE4
6 participants
End of Treatment (Day 42)
2010-02-15
Participant Flow
Study was closed due to an overall low rate of enrollment after only 6 subjects enrolled.
Participant milestones
| Measure |
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.
|
|---|---|
|
Overall Study
STARTED
|
6
|
|
Overall Study
COMPLETED
|
5
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
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.
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|---|---|
|
Overall Study
Adverse Event
|
1
|
Baseline Characteristics
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)
Baseline characteristics by cohort
| Measure |
Anidulalfungin and Voriconazole
n=6 Participants
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.
|
|---|---|
|
Age, Customized
Between 57 and 83 years
|
6 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Anidulalfungin and Voriconazole
n=6 Participants
Anidulafungin and voriconazole in combination followed by monotherapy.
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|---|---|
|
Summary of Global Response at End of Treatment (EOT)
Failure (No response)
|
1 participants
|
|
Summary of Global Response at End of Treatment (EOT)
Partial response
|
3 participants
|
|
Summary of Global Response at End of Treatment (EOT)
Stable response
|
0 participants
|
|
Summary of Global Response at End of Treatment (EOT)
Complete response
|
2 participants
|
SECONDARY outcome
Timeframe: Week 2, Week 4, Week 6Population: 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).
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to Week 6Population: ITT
Number of subects with documented mortality (death).
Outcome measures
| Measure |
Anidulalfungin and Voriconazole
n=6 Participants
Anidulafungin and voriconazole in combination followed by monotherapy.
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|---|---|
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Summary of Mortality
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1 participants
|
SECONDARY outcome
Timeframe: Up to Week 6Population: ITT. No descriptive or inferential analysis was completed due to low enrollment and subsequent early termination of study.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Week 1 through Week 6Population: 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.
Voriconazole trough plasma concentrations measured as nanograms per milliliter (ng/mL).
Outcome measures
Outcome data not reported
Adverse Events
Anidulalfungin and Voriconazole
Serious adverse events
| Measure |
Anidulalfungin and Voriconazole
n=6 participants at risk
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.
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|---|---|
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General disorders
Disease progression
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16.7%
1/6
|
|
Renal and urinary disorders
Renal failure acute
|
16.7%
1/6
|
|
Respiratory, thoracic and mediastinal disorders
Hydropneumothorax
|
16.7%
1/6
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
16.7%
1/6
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
16.7%
1/6
|
Other adverse events
| Measure |
Anidulalfungin and Voriconazole
n=6 participants at risk
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.
|
|---|---|
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Blood and lymphatic system disorders
Anaemia
|
16.7%
1/6
|
|
Blood and lymphatic system disorders
Leukocytosis
|
16.7%
1/6
|
|
Cardiac disorders
Cardiac failure congestive
|
33.3%
2/6
|
|
Gastrointestinal disorders
Diarrhoea
|
16.7%
1/6
|
|
Gastrointestinal disorders
Haematemesis
|
16.7%
1/6
|
|
Gastrointestinal disorders
Nausea
|
16.7%
1/6
|
|
Gastrointestinal disorders
Vomiting
|
33.3%
2/6
|
|
General disorders
Pyrexia
|
16.7%
1/6
|
|
Infections and infestations
Oropharyngeal candidiasis
|
16.7%
1/6
|
|
Investigations
Blood glucose increased
|
16.7%
1/6
|
|
Investigations
Blood magnesium decreased
|
16.7%
1/6
|
|
Investigations
Blood potassium increased
|
16.7%
1/6
|
|
Metabolism and nutrition disorders
Acidosis
|
16.7%
1/6
|
|
Metabolism and nutrition disorders
Hyperphosphataemia
|
16.7%
1/6
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
16.7%
1/6
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
16.7%
1/6
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
16.7%
1/6
|
|
Metabolism and nutrition disorders
Metabolic alkalosis
|
16.7%
1/6
|
|
Psychiatric disorders
Anxiety
|
16.7%
1/6
|
|
Psychiatric disorders
Mental status changes
|
16.7%
1/6
|
|
Skin and subcutaneous tissue disorders
Decubitus ulcer
|
16.7%
1/6
|
|
Skin and subcutaneous tissue disorders
Subcutaneous emphysema
|
16.7%
1/6
|
|
Vascular disorders
Deep vein thrombosis
|
16.7%
1/6
|
|
Vascular disorders
Subclavian vein thrombosis
|
16.7%
1/6
|
|
Vascular disorders
Venous thrombosis limb
|
16.7%
1/6
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of \< 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), \< 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER