Study Will Evaluate The Safety And Efficacy Of Anidulafungin In Patients With Candidemia Or Invasive Candidiasis

Study Overview
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Brief Summary
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The purpose of this study is to further evaluate the safety and effectiveness of intravenous anidulafungin (Eraxis™) in patients with a diagnosis of candidemia or invasive candidiasis, which is a fungus infection of the blood or tissue. Currently the drug is approved for treatment using a daily dose of IV medication until 14 days after the fungus disappears from the blood. This study will evaluate the effectiveness of intravenous anidulafungin when it is administered for 5-28 days followed by oral antifungal medication. Study patients will be assessed for response to treatment throughout the study drug treatment period.

Official Title
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Phase IV Open Label Non Comparative Trial Of IV Anidulafungin Followed By Oral Azole Therapy For The Treatment Of Candidemia And Invasive Candidiasis

Conditions
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Candidiasis

Intervention / Treatment
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* Drug: Eraxis (anidulafungin)
* Drug: Diflucan (fluconazole)
* Drug: Vfend (voriconazole)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects > or equal to 18 years of age. Presence of candidemia (positive blood culture) or invasive candidiasis (histopathologic or cytopathologic examination of a needle aspiration or biopsy specimen from a normally sterile site excluding mucous membranes showing yeast cells) obtained within the prior 96 hours of the screening visit. Subjects who received no more than one prior dose of an echinocandin or polyene. Exclusion Criteria: Subjects with hypersensitivity to anidulafungin, other echinocandins or azoles. Presence of confirmed or suspected Candida osteomyelitis, endocarditis or meningitis. Subjects with infected prosthetic devices which cannot be removed within 24 hours

Ages Eligible for Study
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Minimum Age: 18 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1.<br>Subjects receive anidulafungin IV followed by oral therapy with fluconazole or voriconazole. | Drug: Eraxis (anidulafungin)<br>* Subjects will receive IV anidulafungin (200 mg loading dose followed by 100 mg maintenance doses QD) for 5-28 days. This will be followed by oral therapy with fluconazole at 400 mg once daily or voriconazole at 200 mg twice daily until 14 days after the last positive culture. Fluconazole will be used if the baseline cultures are positive for C. albicans or C. parapsilosis while voriconazole will be used if cultures are positive for C. glabrata or other non-albicans species.<br>Drug: Diflucan (fluconazole)<br>* Subjects will receive IV anidulafungin (200 mg loading dose followed by 100 mg maintenance doses QD) for 5-28 days. This will be followed by oral therapy with fluconazole at 400 mg once daily or voriconazole at 200 mg twice daily until 14 days after the last positive culture. Fluconazole will be used if the baseline cultures are positive for C. albicans or C. parapsilosis.<br>Drug: Vfend (voriconazole)<br>* Subjects will receive IV anidulafungin (200 mg loading dose followed by 100 mg maintenance doses QD) for 5-28 days. This will be followed by oral therapy with fluconazole at 400 mg once daily or voriconazole at 200 mg twice daily until 14 days after the last positive culture. Fluconazole will be used if the baseline cultures are positive for C. albicans or C. parapsilosis while voriconazole will be used if cultures are positive for C. glabrata or other non-albicans species.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Global Response of Success or Failure (Based on Clinical and Microbiological Response) at End of Treatment (EOT) | Success: Clinical response=Cure (no signs, symptoms [s/s] of Candida) or Improvement (significant, incomplete resolution of s/s) and Microbiological response=Eradication (follow up [f/u] culture negative) or Presumed Eradication (f/u culture not available [n/a] and response of clinical success). Failure: Clinical response=Failure (≥3 doses Anidulafungin with no significant improvement in s/s or death due to Candida) and Microbiological response=Persistence (positive culture for ≥1 baseline Candida species [spp]) or Presumed Persistence (f/u culture n/a and clinical outcome= failure). | End of Treatment (Day 5 up to Day 42) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Clinical Response at EOT | Clinical Success=Cure: resolution of Candida s/s or Improvement: significant but incomplete resolution of s/s; Clinical Failure: at least 3 doses Anidulafungin with no significant improvement in s/s or death due to Candida. | End of Treatment (Day 5 up to Day 42) | 
| Number of Participants With Microbiological Response at EOT | Microbiological Success=Eradication: negative culture for baseline Candida spp or Presumed Eradication: f/u culture n/a and clinical outcome defined as success (cure or improvement); Microbiological Failure=Persistence: positive culture for at least 1 baseline Candida spp or Presumed Persistence: f/u culture n/a and clinical outcome defined as failure (≥3 doses Anidulafungin with no significant improvement in s/s or death due to Candida). | End of Treatment (Day 5 up to Day 42) | 
| Number of Participants With Global Response of Success or Failure (Based on Clinical and Microbiological Response) at End of Intravenous Treatment (EOIV) | Success: Clinical response=Cure (s/s of Candida) or Improvement (significant, incomplete resolution of s/s) and Microbiological response=Eradication (f/u culture negative) or Presumed Eradication (f/u culture n/a and response of clinical success). Failure: Clinical response=Failure (≥3 doses Anidulafungin with no significant improvement in s/s or death due to Candida) and Microbiological response=Persistence (positive culture for ≥1 baseline Candida spp) or Presumed Persistence (f/u culture n/a and clinical outcome= failure). | End of Intravenous treatment (Day 5 up to Day 28) | 
| Number of Participants With Clinical Response at EOIV | Clinical Success=Cure: resolution of Candida s/s or Improvement: significant but incomplete resolution of s/s; Clinical Failure: at least 3 doses Anidulafungin with no significant improvement in s/s or death due to Candida. | End of Intravenous treatment (Day 5 up to Day 28) | 
| Number of Participants With Microbiological Response at EOIV | Microbiological Success=Eradication: negative culture for baseline Candida spp or Presumed Eradication: f/u culture n/a and clinical outcome defined as success (cure or improvement); Microbiological Failure=Persistence: positive culture for at least 1 baseline Candida spp or Presumed Persistence: f/u culture n/a and clinical outcome defined as failure (≥3 doses Anidulafungin with no significant improvement in s/s or death due to Candida). | End of Intravenous treatment (Day 5 up to Day 28) | 
| Number of Participants With Sustained (Continued) Global Response of Success or Failure (Based on Clinical and Microbiological Response) at Week 2 Follow-up | Success: Clinical response=Cure (s/s of Candida) or Improvement (significant, incomplete resolution of s/s) and Microbiological response=Eradication (f/u culture negative) or Presumed Eradication (f/u culture n/a and response of clinical success). Failure: Clinical response=Failure (≥3 doses Anidulafungin with no significant improvement in s/s or death due to Candida) and Microbiological response=Persistence (positive culture for ≥1 baseline Candida spp) or Presumed Persistence (f/u culture n/a and clinical outcome= failure). | Week 2 Follow-up | 
| Number of Participants With Sustained (Continued) Clinical Response at Week 2 Follow-up | Clinical Success=Cure: resolution of Candida s/s or Improvement: significant but incomplete resolution of s/s; Clinical Failure: at least 3 doses Anidulafungin with no significant improvement in s/s or death due to Candida. | Week 2 follow-up | 
| Number of Participants With Sustained (Continued) Microbiological Response at Week 2 Follow-up | Microbiological Success=Eradication: negative culture for baseline Candida spp or Presumed Eradication: f/u culture n/a and clinical outcome defined as success (cure or improvement); Microbiological Failure=Persistence: positive culture for at least 1 baseline Candida spp or Presumed Persistence: f/u culture n/a and clinical outcome defined as failure (≥3 doses Anidulafungin with no significant improvement in s/s or death due to Candida). | Week 2 Follow-up | 
| Number of Participants With Sustained (Continued) Global Response of Success or Failure (Based on Clinical and Microbiological Response) at Week 6 Follow-up (End of Study [EOS]) | Success: Clinical response=Cure (s/s of Candida) or Improvement (significant, incomplete resolution of s/s) and Microbiological response=Eradication (f/u culture negative) or Presumed Eradication (f/u culture n/a and response of clinical success). Failure: Clinical response=Failure (≥3 doses Anidulafungin with no significant improvement in s/s or death due to Candida) and Microbiological response=Persistence (positive culture for ≥1 baseline Candida spp) or Presumed Persistence (f/u culture n/a and clinical outcome= failure). | Week 6 Follow-up (EOS) | 
| Number of Participants With Sustained (Continued) Clinical Response at Week 6 Follow-up (EOS) | Clinical Success=Cure: resolution of Candida s/s or Improvement: significant but incomplete resolution of s/s; Clinical Failure: at least 3 doses Anidulafungin with no significant improvement in s/s or death due to Candida. | Week 6 follow-up (EOS) | 
| Number of Participants With Sustained (Continued) Microbiological Response at Week 6 Follow-up (EOS) | Microbiological Success=Eradication: negative culture for baseline Candida spp or Presumed Eradication: f/u culture n/a and clinical outcome defined as success (cure or improvement); Microbiological Failure=Persistence: positive culture for at least 1 baseline Candida spp or Presumed Persistence: f/u culture n/a and clinical outcome defined as failure (≥3 doses Anidulafungin with no significant improvement in s/s or death due to Candida). | Week 6 Follow-up (EOS) | 
| Number of Participants With Global Response of Success or Failure (Based on Clinical and Microbiological Response) at EOT for Participants With Non-albicans Candida at Baseline | Success: Clinical response=Cure (s/s of Candida) or Improvement (significant, incomplete resolution of s/s) and Microbiological response=Eradication (f/u culture negative) or Presumed Eradication (f/u culture n/a and response of clinical success). Failure: Clinical response=Failure (≥3 doses Anidulafungin with no significant improvement in s/s or death due to Candida) and Microbiological response=Persistence (positive culture for ≥1 baseline Candida spp) or Presumed Persistence (f/u culture n/a and clinical outcome= failure). | End of Treatment (Day 5 up to Day 42) | 
| Number of Participants With Global Response of Success or Failure (Based on Clinical and Microbiological Response) at EOIV for Participants With Non-albicans Candida at Baseline | Success: Clinical response=Cure (s/s of Candida) or Improvement (significant, incomplete resolution of s/s) and Microbiological response=Eradication (f/u culture negative) or Presumed Eradication (f/u culture n/a and response of clinical success). Failure: Clinical response=Failure (≥3 doses Anidulafungin with no significant improvement in s/s or death due to Candida) and Microbiological response=Persistence (positive culture for ≥1 baseline Candida spp) or Presumed Persistence (f/u culture n/a and clinical outcome= failure). | End of Intravenous treatment (Day 5 up to Day 28) | 
| Number of Participants With Global Response of Success or Failure (Based on Clinical and Microbiological Response) at Week 2 Follow-up for Participants With Non-albicans Candida at Baseline | Success: Clinical response=Cure (s/s of Candida) or Improvement (significant, incomplete resolution of s/s) and Microbiological response=Eradication (f/u culture negative) or Presumed Eradication (f/u culture n/a and response of clinical success). Failure: Clinical response=Failure (≥3 doses Anidulafungin with no significant improvement in s/s or death due to Candida) and Microbiological response=Persistence (positive culture for ≥1 baseline Candida spp) or Presumed Persistence (f/u culture n/a and clinical outcome= failure). | Week 2 Follow-up | 
| Number of Participants With Global Response of Success or Failure (Based on Clinical and Microbiological Response) at Week 6 Follow-up (EOS) for Participants With Non-albicans Candida at Baseline | Success: Clinical response=Cure (s/s of Candida) or Improvement (significant, incomplete resolution of s/s) and Microbiological response=Eradication (f/u culture negative) or Presumed Eradication (f/u culture n/a and response of clinical success). Failure: Clinical response=Failure (≥3 doses Anidulafungin with no significant improvement in s/s or death due to Candida) and Microbiological response=Persistence (positive culture for ≥1 baseline Candida spp) or Presumed Persistence (f/u culture n/a and clinical outcome= failure). | Week 6 Follow-up (EOS) | 
| Time (75% Quartile Point Estimate) to Negative Blood and / or Tissue Culture for Candida Species | Participants with a negative culture on Day 1 were not included in the analysis. For participants with a positive culture on Day 1, the first day on which there was a negative culture was determined and then compared to the result of the next culture. If the next culture was also negative, or the next culture was positive but the interval between the 2 cultures was > 3 days, the earlier of the 2 cultures was the day of first negative blood culture. If next culture was positive and taken within 3 days of the previous culture, the process was repeated with the next negative blood culture. | Baseline (Day 1) up to Week 6 Follow-up (EOS) | 
| Medical Resource Utilization (MRU): Duration of Hospital Stay (Days) | Measured as time to dischargeable (medically dischargeable status) and as time to discharge (actual discharge). Analysis of length of hospital stay based on Kaplan-Meier survival techniques. | Baseline up to 6 Week Follow-up (EOS) | 
| Medical Resource Utilization (MRU): Duration of Intensive Care Unit or Critical Care Unit Stay (Days) | Analysis of length of hospital stay based on Kaplan-Meier survival techniques. | Baseline up to 6 Week Follow-up (EOS) | 
| Medical Resource Utilization (MRU): Duration of Intravenous Therapy (Days) | Analysis of length of hospital stay based on Kaplan-Meier survival techniques. | Baseline up to End of Intravenous treatment (Day 5 up to Day 28) | 
| Medical Resource Utilization (MRU): Duration of Overall Therapy (Days) | Overall therapy includes Intravenous and Oral therapy. Participants were to receive at least 5 days and a maximum of 28 days of IV anidulafungin. After that, participants could continue treatment with oral fluconazole or voriconazole for at least 14 days from the day of last positive culture. | Baseline up to End of Treatment (Day 5 up to Day 42) | 
| Number of Participants Per Specified Cause of Death | Cause of death (includes all-cause and attributable to Candida infection) reported based on death due to Serious Adverse Events (SAEs). SAEs are any untoward medical occurrence at any dose that results in death, is life threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, results in congenital anomaly or birth defect. Participants may be counted with > 1 cause of death if multiple causes were present. | Baseline up to Week 6 Follow-up (EOS) or 30 days after last dose of study drug (whichever was later) | 
| Number of Participants With Non-serious and Serious Adverse Events | AEs are any untoward medical occurrence in a clinical investigation subject administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. SAEs are any untoward medical occurrence at any dose that results in death, is life threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, results in congenital anomaly or birth defect. | Baseline up to Week 6 Follow-up (EOS) or 30 days after last dose of study drug (whichever was later) | 
| Number of Participants Who Died |  | Baseline up to Week 6 Follow-up (EOS) or 30 days after last dose of study drug (whichever was later) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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candidemia, invasive candidiasis, fungal bloodstream infection