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

This study has been completed.
Sponsor:
Information provided by:
Pfizer
ClinicalTrials.gov Identifier:
NCT00548262
First received: October 19, 2007
Last updated: December 15, 2010
Last verified: December 2010
  Purpose

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.


Condition Intervention Phase
Candidemia
Invasive Candidiasis
Drug: Anidulafungin
Drug: Voriconazole
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Open-Label, Non-Comparative, Study Of Intravenous Anidulafungin, Followed Optionally By Oral Voriconazole, For Treatment Of Documented Candidemia/Invasive Candidiasis In Hospitalized Patients

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Number of Participants for Global Response (Based on Clinical and Microbiological Success or Failure) at End of Treatment [ Time Frame: End of Treatment (EOT) (up to Day 42) ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • Number of Participants for Global Response (Based on Clinical and Microbiological Success or Failure) [ Time Frame: End of Intravenous Treatment (EIVT) (up to Day 42), Week 2 Follow-up ] [ Designated as safety issue: No ]
    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).

  • Number of Participants for Global Response Per Type of Candida Species Isolated at Baseline: EIVT [ Time Frame: Baseline, EIVT (up to Day 42) ] [ Designated as safety issue: No ]
    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.

  • Number of Participants for Global Response Per Type of Candida Species Isolated at Baseline: EOT [ Time Frame: Baseline, EOT (up to Day 42) ] [ Designated as safety issue: No ]
    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.

  • Number of Participants for Global Response Per Type of Candida Species Isolated at Baseline: Week 2 Follow-up [ Time Frame: Baseline, Week 2 Follow-up ] [ Designated as safety issue: No ]
    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.

  • Number of Participants for Global Response for Pre-specified Baseline Risk Factors Subgroups of Interest: EOT [ Time Frame: Baseline, EOT (up to Day 42) ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants for Global Response for Baseline Risk Factors for Candidemia and Invasive Candidiasis: EIVT [ Time Frame: EIVT (up to Day 42) ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants for Global Response for Baseline Risk Factors for Candidemia and Invasive Candidiasis: Week 2 Follow-up [ Time Frame: Baseline, Week 2 Follow-up (F/U) ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants for Global Response by Acute Physiological Assessment and Chronic Health Evaluation II (APACHE II) Score [ Time Frame: EIVT (up to Day 42), EOT (up to Day 42), Week 2 Follow-up ] [ Designated as safety issue: No ]
    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.

  • Number of Participants Per Survival Status (Alive or Dead) on Day 30 [ Time Frame: Day 30 ] [ Designated as safety issue: No ]
  • Number of Participants With Death Attributable (Yes or No) to Candidemia or Invasive Candidiasis [ Time Frame: Baseline to Week 6 Follow-up ] [ Designated as safety issue: Yes ]
    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.

  • Time to Negative Blood, Specimen, or Tissue Culture [ Time Frame: Baseline to Week 2 Follow-up ] [ Designated as safety issue: No ]
    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).

  • Duration of Exposure to Intravenous Anidulafungin Prior to Switch to Oral Voriconazole Treatment [ Time Frame: Baseline to Day 42 ] [ Designated as safety issue: No ]
    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.

  • Length of Hospital Stay [ Time Frame: Baseline to Week 6 Follow-up ] [ Designated as safety issue: No ]
    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.

  • Length of Stay in Intensive Care Unit (ICU) [ Time Frame: Baseline up to Week 6 Follow-up ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Vital Signs: Supine Blood Pressure [ Time Frame: Baseline to Week 2 Follow-up ] [ Designated as safety issue: Yes ]
    Supine systolic and diastolic blood pressure BP) measured as millimeters of mercury (mmHg).

  • Change From Baseline in Vital Signs: Supine Heart Rate [ Time Frame: Baseline to Week 2 Follow-up ] [ Designated as safety issue: Yes ]
    Supine heart rate measured as beats per minute (bpm).

  • Change From Baseline in Vital Signs: Weight [ Time Frame: Baseline to Week 2 Follow-up ] [ Designated as safety issue: Yes ]
    Weight measured as kilograms (kg).

  • Change From Baseline in Vital Signs: Temperature [ Time Frame: Baseline to Week 2 Follow-up ] [ Designated as safety issue: Yes ]
    Temperature measured as degrees of Celsius (C).

  • Change From Baseline in Vital Signs: Respiration Rate [ Time Frame: Baseline to Week 2 Follow-up ] [ Designated as safety issue: Yes ]
    Respiration rate measured as respirations per minute (resp/min).

  • Change From Baseline in Chemistry Laboratory Test Data (Measured as mg/dL) [ Time Frame: Baseline to Week 2 Follow-up ] [ Designated as safety issue: Yes ]
    Chemistry laboratory test data measured as milligrams per deciliter (mg/dL).

  • Change From Baseline in Chemistry Laboratory Test Data (Measured as IU/L) [ Time Frame: Baseline to Week 2 Follow-up ] [ Designated as safety issue: Yes ]
    Chemistry laboratory test data measured as international units per (IU/L).


Enrollment: 54
Study Start Date: February 2008
Study Completion Date: October 2009
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: Anidulafungin
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.
Other Name: Eraxis
Drug: Voriconazole
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).
Other Name: Vfend

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00548262

Locations
Brazil
Pfizer Investigational Site
Brasilia, DF, Brazil, 70710-905
Pfizer Investigational Site
Curitiba, PR, Brazil, 80060-900
Pfizer Investigational Site
Rio de Janeiro, RJ, Brazil, 21941-913
Pfizer Investigational Site
Porto Alegre, RS, Brazil, 90020-090
Pfizer Investigational Site
Porto Alegre, RS, Brazil, 90110-270
Pfizer Investigational Site
Sao Jose do Rio Preto, SP, Brazil, 15090-000
Chile
Pfizer Investigational Site
Independencia, Santiago, RM, Chile, 8380456
Colombia
Pfizer Investigational Site
Bogota DC, Cundinamarca, Colombia, 0000
Pfizer Investigational Site
Cali, Valle Del Cauca, Colombia, 0000
Mexico
Pfizer Investigational Site
Leon, Guanajuato, Mexico, 37320
Pfizer Investigational Site
Guadalajara, Jalisco, Mexico, 44280
Pfizer Investigational Site
San Luis Potosi, Mexico, 78240
Panama
Pfizer Investigational Site
Panama, Panama
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer, Inc.
ClinicalTrials.gov Identifier: NCT00548262     History of Changes
Other Study ID Numbers: A8851015
Study First Received: October 19, 2007
Results First Received: October 6, 2010
Last Updated: December 15, 2010
Health Authority: Brazil: Agencia Nacional de Vigilância Sanitária / Conselho Nacional de Ética em Pesquisa

Keywords provided by Pfizer:
Open-label
non-comparative study to evaluate short course of IV anidulafungin
followed by oral voriconazole
for tx of candidemia/invasive candidiasis.

Additional relevant MeSH terms:
Candidemia
Candidiasis
Candidiasis, Invasive
Fungemia
Infection
Inflammation
Mycoses
Pathologic Processes
Sepsis
Systemic Inflammatory Response Syndrome
Anidulafungin
Echinocandins
Voriconazole
14-alpha Demethylase Inhibitors
Anti-Infective Agents
Antifungal Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014