This Is An Open-Label, Non-Comparative Study Designed To Evaluate A Short Course Of IV Anidulafungin, Followed Optionally By Oral Voriconazole, For The Treatment Of Candidemia And Invasive Candidiasis

Study Overview
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Brief Summary
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The primary objective is to estimate global response rate. Clinical, microbiological and global response rates and its 95% confidence intervals will be computed. No hypotheses will be tested.

Official Title
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Open-Label, Non-Comparative, Study Of Intravenous Anidulafungin, Followed Optionally By Oral Voriconazole, For Treatment Of Documented Candidemia/Invasive Candidiasis In Hospitalized Patients

Conditions
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Candidemia, Invasive Candidiasis

Intervention / Treatment
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* Drug: Anidulafungin
* Drug: Voriconazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patient 18 years of age and older. If female, must be post-menopausal, surgically sterile or using adequate contraception,not lactating, and have a negative urine or blood pregnancy test at screening, prior to administration of study medication. 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 to study entry ((informed consent provided). Presence of one or more of the following signs and symptoms of acute fungal infection within the prior 48 hours to initiation of study treatment: Fever defined as oral temperature greater than or equal to 38 degrees C (100.4 degrees F); rectal or core temperature greater than or equal to 38.6 degrees C (101.4 degrees F), or axillary temperature greater than or equal to 37.5 degrees Celsius (99.5 degrees F). Hypothermia defined as rectal or core temperature less than 36.0 degrees C (96.8 degrees F). Hypotension (systolic blood pressure [SBP] less than 100 mmHg, or SBP decrease greater than or equal to 30 mm Hg from baseline. Localized signs and symptoms of inflammation (swelling, heat, erythema or purulence at a site infected with Candida spp.). Patient is classified in one of following categories based on previous antifungal treatment: received less than 48 hours of previous systemic antifungal therapy and no more than a single dose of echinocandin therapy prior to study entry; intolerant to infusion related toxicities of amphotericin B preparations despite appropriate supportive measures or serum creatinine increased by >1.5 mg/dl while receiving conventional or lipid amphotericin B therapy; or lack of clinical response and/or persistent positive blood culture after at least seven days of systemic antifungal treatment with a polyene or fluconazole at an adequate dose. APACHE II 9 score < 25 at study entry. Patients willing and able to give informed consent, or have a legally authorized representative willing to give informed consent on the patients behalf. Expected survival (in the opinion of the investigator) greater than 4 days. Exclusion Criteria: Hypersensitivity to anidulafungin, other echinocandins or azoles. Participation presently or within the last 30 days in a trial with other investigational drug(s). Patients on antiretroviral or chemotherapy regimens which include an investigational drug may participate provided that there has been no change in their therapy during the past 4 weeks and no change in treatment is anticipated during study participation. Chronic refractory neutropenia defined as absolute neutrophils count <500 cells/mm3 for 28 days prior to the baseline visit. Confirmed or suspected Candida osteomyelitis, endocarditis or meningitis. Poor venous access that would preclude IV drug delivery or multiple blood draws. Prosthetic devices at a suspected site of infection unless the device is removed within 24 hours of study entry. Fungal endophthalmitis confirmed by fundoscopy. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration that may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the Patient inappropriate for entry into this trial.

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> | Drug: Anidulafungin<br>* All patients will receive anidulafungin 200 mg IV dose on Day 1. On Day 2 and daily thereafter the patients will receive one daily IV dose of 100 mg of anidulafungin.<br>* Other names: Eraxis;Drug: Voriconazole<br>* Patients who complete a minimum of 5 days of IV treatment with anidulafungin may be switched to oral voriconazole 200 mg BID (or 100 mg BID if <40 kg body weight) therapy on Day 5 and thereafter, starting with a loading dose of 400 mg BID (or 200 mg BID if <40 kg body weight).<br>* Other names: Vfend;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants for Global Response (Based on Clinical and Microbiological Success or Failure) at End of Treatment | Clinical Success (cure=resolution of Candida signs and symptoms [s/s] or improvement=significant but incomplete resolution of s/s) or Failure (at least 3 doses Anidulafungin with no significant improvement in s/s or death due to Candida) and Microbiological Success (eradication=negative culture for baseline Candida species (spp) or presumed eradication=follow-up (f/u) culture not available (n/a) and clinical outcome defined as success) or 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). | End of Treatment (EOT) (up to Day 42) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants for Global Response (Based on Clinical and Microbiological Success or Failure) | Clinical Success (cure=resolution of Candida signs and symptoms [s/s] or improvement=significant but incomplete resolution of s/s) or Failure (at least 3 doses Anidulafungin with no significant improvement in s/s or death due to Candida) and Microbiological Success (eradication=negative culture for baseline Candida species (spp) or presumed eradication=follow-up (f/u) culture not available (n/a) and clinical outcome defined as success) or 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). | End of Intravenous Treatment (EIVT) (up to Day 42), Week 2 Follow-up | 
| Number of Participants for Global Response Per Type of Candida Species Isolated at Baseline: EIVT | Global response based on assessments of Clinical Success or Failure and Microbiological Success or Failure. Categorized as global Success if both clinical and microbiological response=success; Failure defined as all other combinations. Global response at EIVT was assessed per the type of Candida species that was isolated at the baseline visit. | Baseline, EIVT (up to Day 42) | 
| Number of Participants for Global Response Per Type of Candida Species Isolated at Baseline: EOT | Global response based on assessments of Clinical Success or Failure and Microbiological Success or Failure. Categorized as global Success if both clinical and microbiological response=success; Failure defined as all other combinations. Global response at EOT was assessed per the type of Candida species that was isolated at the baseline visit. | Baseline, EOT (up to Day 42) | 
| Number of Participants for Global Response Per Type of Candida Species Isolated at Baseline: Week 2 Follow-up | Global response based on assessments of Clinical Success or Failure and Microbiological Success or Failure. Categorized as global Success if both clinical and microbiological response=success; Failure defined as all other combinations. Global response at Week 2 Follow-up was assessed per the type of Candida species that was isolated at the baseline visit. | Baseline, Week 2 Follow-up | 
| Number of Participants for Global Response for Pre-specified Baseline Risk Factors Subgroups of Interest: EOT | Global response based on assessments of Clinical Success or Failure and Microbiological Success or Failure. Global response at EOT was assessed for participants categorized with baseline risk factors (Yes or No status) for Intensive Care Unit (ICU) stay ≥ 4 days, mechanical ventilation, broad spectrum antibiotics (antibiotics), central venous (CV) catheter, total parental nutrition (TPN), dialysis, abdominal surgery, solid organ transplant, renal insufficiency, chemotherapy, pancreatitis, systemic steroids or immunosuppressives (Systemic steroids/immunos), neutropenic status, or elderly. | Baseline, EOT (up to Day 42) | 
| Number of Participants for Global Response for Baseline Risk Factors for Candidemia and Invasive Candidiasis: EIVT | Global response based on assessments of Clinical Success or Failure and Microbiological Success or Failure. Global response at EIVT was assessed for participants categorized with baseline risk factors for Candidemia and Invasive Candidiasis: ICU stay ≥ 4 days, mechanical ventilation, broad spectrum antibiotics (antibiotics), central venous (CV) catheter, total parental nutrition (TPN), dialysis, abdominal surgery, solid organ transplant, renal insufficiency, chemotherapy, pancreatitis, systemic steroids or immunosuppressives (Systemic steroids/immunos), neutropenic status, or elderly. | EIVT (up to Day 42) | 
| Number of Participants for Global Response for Baseline Risk Factors for Candidemia and Invasive Candidiasis: Week 2 Follow-up | Global response based on assessments of Clinical Success or Failure and Microbiological Success or Failure. Global response at Week 2 F/U was assessed for participants categorized with baseline risk factors for Candidemia and Invasive Candidiasis: ICU stay ≥ 4 days, mechanical ventilation, broad spectrum antibiotics (antibiotics), central venous (CV) catheter, total parental nutrition (TPN), dialysis, abdominal surgery, solid organ transplant, renal insufficiency, chemotherapy, pancreatitis, systemic steroids or immunosuppressives (Systemic steroids/immunos), neutropenic status, or elderly. | Baseline, Week 2 Follow-up (F/U) | 
| Number of Participants for Global Response by Acute Physiological Assessment and Chronic Health Evaluation II (APACHE II) Score | Global response based on assessments of Clinical Success or Failure and Microbiological Success or Failure. Categorized as global Success if both clinical and microbiological response=success; Failure defined as all other combinations. Global response assessed as APACHE II score <20 (less affected) or ≥20 (more severe). APACHE II assesses severity of illness in acutely ill participants; measurements computed for physiologic variables were transformed to integer score ranging 0 (normal) to 71 (more severe). Higher scores indicate more severe disease and higher risk of death. | EIVT (up to Day 42), EOT (up to Day 42), Week 2 Follow-up | 
| Number of Participants Per Survival Status (Alive or Dead) on Day 30 |  | Day 30 | 
| Number of Participants With Death Attributable (Yes or No) to Candidemia or Invasive Candidiasis | Death is attributable to Candidemia or Invasive Candidiasis if investigator recorded disease under study as cause of death. Candidemia (positive blood culture) or Invasive Cadidiasis (yeast cells in histopathological or cytopathological exam). Week 6 Follow-up visit conducted by phone. | Baseline to Week 6 Follow-up | 
| Time to Negative Blood, Specimen, or Tissue Culture | Defined as time from first drug administratin to date of earliest recorded documentation of negative blood, specimen, or tissue culture (absence of Candidemia or Invasive Candidiasis). Candidemia (positive blood culture) or Invasive Cadidiasis (yeast cells in histopathological or cytopathological exam). | Baseline to Week 2 Follow-up | 
| Duration of Exposure to Intravenous Anidulafungin Prior to Switch to Oral Voriconazole Treatment | Defined as time in days from first intravenous administration of Anidulafungin to the date of earliest recorded documentation of switch to oral Voriconazole treatment. Participants received at least 5 days (and a maximum of 42 days) of IV Anidulafungin; after this, they may continue treatment with oral Voriconazole for at least 14 days from the day of last positive culture up to a maximum of 42 days. | Baseline to Day 42 | 
| Length of Hospital Stay | Defined as the number of days from date of first drug administration to date of first hospital discharge if participant was discharged to home or other location. Week 6 Follow-up visit conducted by phone. | Baseline to Week 6 Follow-up | 
| Length of Stay in Intensive Care Unit (ICU) | Defined as the number of days from date of first drug administration to date of first ICU discharge. Week 6 Follow-up visit conducted by phone. | Baseline up to Week 6 Follow-up | 
| Change From Baseline in Vital Signs: Supine Blood Pressure | Supine systolic and diastolic blood pressure BP) measured as millimeters of mercury (mmHg). | Baseline to Week 2 Follow-up | 
| Change From Baseline in Vital Signs: Supine Heart Rate | Supine heart rate measured as beats per minute (bpm). | Baseline to Week 2 Follow-up | 
| Change From Baseline in Vital Signs: Weight | Weight measured as kilograms (kg). | Baseline to Week 2 Follow-up | 
| Change From Baseline in Vital Signs: Temperature | Temperature measured as degrees of Celsius (C). | Baseline to Week 2 Follow-up | 
| Change From Baseline in Vital Signs: Respiration Rate | Respiration rate measured as respirations per minute (resp/min). | Baseline to Week 2 Follow-up | 
| Change From Baseline in Chemistry Laboratory Test Data (Measured as mg/dL) | Chemistry laboratory test data measured as milligrams per deciliter (mg/dL). | Baseline to Week 2 Follow-up | 
| Change From Baseline in Chemistry Laboratory Test Data (Measured as IU/L) | Chemistry laboratory test data measured as international units per (IU/L). | Baseline to Week 2 Follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Open-label, non-comparative study to evaluate short course of IV anidulafungin, followed by oral voriconazole, for tx of candidemia/invasive candidiasis.