An Evaluation Of The Effectiveness And Safety Of Anidulafungin Compared To Caspofungin For The Treatment Of Serious Fungal Infection Due To Candida In Patients With A Dysfunctional Immune System

Study Overview
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Brief Summary
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The purpose of this study is to gather information on the use of anidulafungin for the treatment of Candida infection in patients with an abnormal immune system. It is expected that anidulafungin will be at least as safe and as effective as the comparator drug, caspofungin.

Official Title
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Efficacy And Safety Of Eraxis/Ecalta (Anidulafungin) Compared To Cancidas (Caspofungin) In Neutropenic Patients With Invasive Candida Infection

Conditions
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Fungemia, Neutropenia, Candidiasis

Intervention / Treatment
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* Drug: Active Anidulafungin
* Drug: Active Caspofungin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Dysfunctional immune system (reduced neutrophils). Confirmed Candida infection, defined as growth of Candida from a normally sterile site accompanied by signs and symptoms of infection. Male of female ≥16 years of age. Expected hospitalization for at least ten (10) days. Exclusion Criteria: Pregnancy or breast feeding or planning to become pregnant during the study. Recent treatment with one of the study drugs over the last 30 days. Allergy to either study drug or to this class of drugs. Significant liver dysfunction. Suspected Candida osteomyelitis, endocarditis, meningitis or any other infections of the central nervous system.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anidulafungin Arm<br>Subjects were randomized 2:1 (anidulafungin:caspofunin). | Drug: Active Anidulafungin<br>* Subjects in this arm will receive active anidulafungin and placebo caspofungin<br>|
| Experimental: Caspofungin Arm<br>Subjects were randomized 2:1 (anidulafungin:caspofunin). | Drug: Active Caspofungin<br>* Subjects in this arm will receive active caspofungin and placebo anidulafungin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global Response at End of Intravenous Treatment (EOIVT) | Participant counts of global response of success, failure, or indeterminate. Success: clinical response of cure (no signs, symptoms [s/s] of Candida) or improvement (significant, incomplete resolution of s/s) and microbiological response of eradication (follow-up [f/u] culture negative) or presumed eradication (f/u culture not available and clinical success). Failure: clinical response of failure (greater than or equal to [≥3] doses study medication and no significant improvement of s/s or death due to Candida) and/or unsuccessful microbiological response of persistent(positive culture any Candida species [sp]), new infection or relapse at f/u. Indeterminate: clinical and/or microbiological response of indeterminate (evaluation could not be made due to withdrawal from study prior to assessment of cure or failure) and there was neither clinical response of failure nor unsuccessful microbiological response (persistence or new infection or relapse). | Day 10 up to Day 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global Response at End of Treatment (EOT) | Participant counts of global response of success, failure, or indeterminate. Success: clinical response of cure (no s/s of Candida) or improvement (significant, incomplete resolution of s/s) and microbiological response of eradication (f/u culture negative) or presumed eradication (f/u culture not available and clinical success). Failure: clinical response of failure (≥3 doses study medication and no significant improvement of s/s or death due to Candida) and/or unsuccessful microbiological response of persistent (positive culture any Candida sp), new infection or relapse at f/u. Indeterminate: clinical and/or microbiological response of indeterminate (evaluation could not be made due to withdrawal from study prior to assessment of cure or failure) and there was neither clinical response of failure nor unsuccessful microbiological response (persistence or new infection or relapse). | Day 14 up to Day 56 | 
| Global Response at 2-Week Follow-Up Visit | Participant counts of global response of success, failure, or indeterminate. Success: clinical response of cure (no s/s of Candida) or improvement (significant, incomplete resolution of s/s) and microbiological response of eradication (f/u culture negative) or presumed eradication (f/u culture not available and clinical success). Failure: clinical response of failure (≥3 doses study medication and no significant improvement of s/s or death due to Candida) and/or unsuccessful microbiological response of persistent (positive culture any Candida sp), new infection or relapse at f/u. Indeterminate: clinical and/or microbiological response of indeterminate (evaluation could not be made due to withdrawal from study prior to assessment of cure or failure) and there was neither clinical response of failure nor unsuccessful microbiological response (persistence or new infection or relapse). | 2 weeks post treatment | 
| Global Response at 6-Week Follow-Up Visit | Participant counts of global response of success, failure, or indeterminate. Success: clinical response of cure (no s/s of Candida) or improvement (significant, incomplete resolution of s/s) and microbiological response of eradication (f/u culture negative) or presumed eradication (f/u culture not available and clinical success). Failure: clinical response of failure (≥3 doses study medication and no significant improvement of s/s or death due to Candida) and/or unsuccessful microbiological response of persistent (positive culture any Candida sp), new infection or relapse at f/u. Indeterminate: clinical and/or microbiological response of indeterminate (evaluation could not be made due to withdrawal from study prior to assessment of cure or failure) and there was neither clinical response of failure nor unsuccessful microbiological response (persistence or new infection or relapse). | 6 weeks post treatment | 
| Response Based on Clinical Cure and Microbiological Success at EOIVT | Participant counts of clinical cure (no s/s of Candida) and microbiological success (eradication [f/u culture negative] or presumed eradication [f/u culture not available and a clinical response of cure]). | Day 10 up to Day 42 | 
| Response Based on Clinical Cure and Microbiological Success at EOT | Participant counts of clinical cure (no s/s of Candida) and microbiological success (eradication [f/u culture negative] or presumed eradication [f/u culture not available and a clinical response of cure]). | Day 14 up to Day 56 | 
| Response Based on Clinical Cure and Microbiological Success at 2-Week Follow-Up Visit | Participant counts of clinical cure (no s/s of Candida) and microbiological success (eradication [f/u culture negative] or presumed eradication [f/u culture not available and a clinical response of cure]). | 2 weeks post treatment | 
| Response Based on Clinical Cure and Microbiological Success at 6-Week Follow-Up Visit | Participant counts of clinical cure (no s/s of Candida) and microbiological success (eradication [f/u culture negative] or presumed eradication [f/u culture not available and a clinical response of cure]). | 6 weeks post treatment | 
| Clinical Response at Day 10 | Participant counts of clinical response categorized as success, failure, or indeterminate. Success: no s/s of Candida (cure) or significant but incomplete resolution of s/s of Candida; no additional systemic or oral antifungal treatment required (improvement). Failure: worsening of s/s of the Candida infection. Indeterminate: evaluation could not be made due to withdrawal from study prior to assessment of cure or failure. Participants who received fewer than 3 doses of study medication were assigned a clinical efficacy response of indeterminate. | Day 10 | 
| Number of Participants With Recurrence | Participant counts of microbiologic response of recurrence defined as any baseline Candida sp isolated following eradication, or culture data were not available for participants with a clinical response of failure after a previous response of success. Clinical failure defined as ≥3 doses study medication and no significant improvement of s/s or death due to Candida. Clinical success is resolution of s/s and no additional antifungal treatment needed. | 2 and 6 weeks post treatment | 
| Number of Participants With New Infections | Participant counts of microbiologic response of new infection defined as clinical failure with emergence of new Candida sp not identified at baseline at the original site of infection or at a distant site of infection. Clinical failure defined as ≥3 doses study medication and no significant improvement of s/s or death due to Candida. | 2 and 6 weeks post treatment | 
| Time to First Negative Blood Culture for Candida Species | A participant had a negative blood culture, if having determined the day of the first negative blood culture, the subsequent blood culture was also negative, or if positive, the interval between the cultures was at least 2 days. For participants whose blood culture went from positive to negative, the time to negative blood culture defined as: date of first negative blood culture minus first treatment date plus 1. | Baseline up to Day 56 | 
| Time to Death | Time to death defined as: date of death minus first treatment date plus 1. | Day 1 up to Day 98 | 
| All-Cause Mortality | All-cause mortality during study therapy and at follow-up visits reported as unique deaths at EOIVT, end of oral treatment (EOT-oral), 2 Week Follow-Up and 6 Week Follow-Up | Baseline up to 6 weeks post treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Candidiasis; Invasive Candidiasis; Candida; Candidemia; Fungal Infection; Neutropenia