Anidulafungin Plus Voriconazole Versus Voriconazole For The Treatment Of Invasive Aspergillosis

Study Overview
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Brief Summary
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This study compares the effectiveness and safety of the combination of anidulafungin and voriconazole compared to that of voriconazole alone (which is generally considered the standard of care) for the treatment of Invasive Aspergillosis.

Official Title
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A Prospective, Randomized Trial Comparing The Efficacy Of Anidulafungin And Voriconazole In Combination To That Of Voriconazole Alone When Used For Primary Therapy Of Proven Or Probable Invasive Aspergillosis

Conditions
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Aspergillosis

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Immunocompromised state due to either 1. receipt of hematopoeitic stem cell transplantation or 2. hematologic malignancy; Diagnosis of possible, probable, or proven invasive aspergillosis. Exclusion Criteria: Patients with aspergilloma or chronic aspergillosis Receipt of 4 or more days of systemic antifungal treatment for the current episode of invasive aspergillosis Anticipated survival of less than 5 days or Karnofsky score <=20

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Voriconazole<br>Voriconazole monotherapy | Drug: voriconazole<br>* First week: Voriconazole 6 mg/kg IV bid for the first 24 hours, followed by 4 mg/kg IV BID plus anidulafungin placebo IV qd. Second week: Voriconazole 4 mg/kg IV bid or 300 mg PO bid plus anidulafungin placebo IV qd. Third and fourth weeks: Voriconazole 4 mg/kg IV bid OR 300 mg PO bid plus anidulafungin placebo IV qd, OR Voriconazole 4 mg/kg IV bid or 300 mg PO bid monotherapy. Fifth and sixth weeks: Voriconazole 4 mg/kg IV bid or 300 mg PO bid monotherapy.<br>* Other names: Vfend;|
| Experimental: Voriconazole and Anidulafungin<br>Combination therapy with voriconazole and anidulafungin | Drug: anidulafungin<br>* First week: Voriconazole 6 mg/kg IV bid for the first 24 hours, followed by 4 mg/kg IV bid plus anidulafungin 200 mg IV on day 1, followed by 100 mg IV qd thereafter. Second week: Voriconazole 4 mg/kg IV bid or 300 mg PO bid plus anidulafungin 100 mg IV qd. Third and fourth weeks: Voriconazole 4 mg/kg IV bid OR 300 mg PO bid plus anidulafungin 100 mg IV qd, OR Voriconazole 4 mg/kg IV bid or 300 mg PO bid monotherapy. Fifth and sixth weeks: Voriconazole 4 mg/kg IV bid or 300 mg PO bid monotherapy.<br>* Other names: Eraxis;Drug: voriconazole<br>* First week: Voriconazole 6 mg/kg IV bid for the first 24 hours, followed by 4 mg/kg IV bid plus anidulafungin 200 mg IV on day 1, followed by 100 mg IV qd thereafter. Second week: Voriconazole 4 mg/kg IV bid or 300 mg PO bid plus anidulafungin 100 mg IV qd. Third and fourth weeks: Voriconazole 4 mg/kg IV bid OR 300 mg PO bid plus anidulafungin 100 mg IV qd, OR Voriconazole 4 mg/kg IV bid or 300 mg PO bid monotherapy. Fifth and sixth weeks: Voriconazole 4 mg/kg IV bid or 300 mg PO bid monotherapy.<br>* Other names: Vfend;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause Mortality at Week 6 in Participants With Proven or Probable Invasive Aspergillosis | Number of deaths measured 6 weeks after start of treatment. Time to death defined as date of death minus first treatment date + 1. | Day 1 to Day 42 (Week 6) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global Response at Week 6 | Number of participants with a successful response (complete or partial global response). Complete response = resolution of all clinical signs and symptoms and >90% of lesions due to IA that were visible on radiologic studies at baseline (BL); partial response = clinical improvement and >50% improvement in radiological findings present at BL. | Baseline, Day 42 (Week 6) | 
| All-cause Mortality at Week 6 in Participants With Possible, Probable, or Proven Invasive Aspergillosis (IA) | Number of deaths due to any cause measured 6 weeks after start of treatment. Time to death defined as date of death minus first treatment date + 1. | Day 1 to Day 42 (Week 6) | 
| All-cause Mortality at Week 12 in Participants With Probable or Proven Invasive Aspergillosis (IA) | Number of deaths due to any cause measured 12 weeks after start of treatment. Time to death defined as date of death minus first treatment date + 1. | Day 1 to Day 84 (Week 12) | 
| Mortality Due to Invasive Aspergillosis (IA) at Week 6 in Participants With Probable or Proven IA | Number of deaths due to Invasive Aspergillosis measured 6 weeks after start of treatment. Time to death defined as date of death minus first treatment date + 1. | Day 1 to Day 42 (Week 6) | 
| Time to Death: All-Cause Mortality | Survival time from start of treatment. Time to death defined as date of death due to any cause minus first treatment date + 1. | Day 1 to Day 84 (Week 12) | 
| Time to Death Due to Invasive Aspergillosis (IA) | Survival time from start of treatment. Time to death defined as date of death due to IA minus first treatment date + 1. | Day 1 to Day 84 (Week 12) |