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

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

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.

Study Overview

• Status: Terminated
• Conditions: Candidiasis; Fungemia; Neutropenia
• Intervention / Treatment: Drug: Active Caspofungin; Drug: Active Anidulafungin

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bosnia and Herzegovina
  • Sarajevo, Bosnia and Herzegovina, 71000
    • Pfizer Investigational Site
• France
  • GRENOBLE Cedex 09, France, 38043
    • Pfizer Investigational Site
  • Strasbourg Cedex, France, 67098
    • Pfizer Investigational Site
• Italy
  • Bologna, Italy, 40138
    • Pfizer Investigational Site
  • Roma, Italy, 00133
    • Pfizer Investigational Site
• Poland
  • Gdansk, Poland, 80-952
    • Pfizer Investigational Site
  • Warszawa, Poland, 02-776
    • Pfizer Investigational Site
  • Wroclaw, Poland, 50-367
    • Pfizer Investigational Site
• Russian Federation
  • Moscow, Russian Federation, 115478
    • Pfizer Investigational Site
• Slovakia
  • Kosice, Slovakia, 04190
    • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Anidulafungin Arm; Subjects were randomized 2:1 (anidulafungin:caspofunin).	Drug: Active Anidulafungin; Subjects in this arm will receive active anidulafungin and placebo caspofungin
EXPERIMENTAL: Caspofungin Arm; Subjects were randomized 2:1 (anidulafungin:caspofunin).	Drug: Active Caspofungin; Subjects in this arm will receive active caspofungin and placebo anidulafungin

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• De Rosa FG, Busca A, Capparella MR, Yan JL, Aram JA. Invasive Candidiasis in Patients with Solid Tumors Treated with Anidulafungin: A Post Hoc Analysis of Efficacy and Safety of Six Pooled Studies. Clin Drug Investig. 2021 Jun;41(6):539-548. doi: 10.1007/s40261-021-01024-7. Epub 2021 Apr 23.
• Kontoyiannis DP, Bassetti M, Nucci M, Capparella MR, Yan JL, Aram J, Hogan PA. Anidulafungin for the treatment of candidaemia caused by Candida parapsilosis: Analysis of pooled data from six prospective clinical studies. Mycoses. 2017 Oct;60(10):663-667. doi: 10.1111/myc.12641. Epub 2017 Jun 9.
• Kullberg BJ, Vasquez J, Mootsikapun P, Nucci M, Paiva JA, Garbino J, Yan JL, Aram J, Capparella MR, Conte U, Schlamm H, Swanson R, Herbrecht R. Efficacy of anidulafungin in 539 patients with invasive candidiasis: a patient-level pooled analysis of six clinical trials. J Antimicrob Chemother. 2017 Aug 1;72(8):2368-2377. doi: 10.1093/jac/dkx116.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (ACTUAL): October 1, 2011
• Study Completion (ACTUAL): October 1, 2011

Study Registration Dates

• First Submitted: November 26, 2008
• First Submitted That Met QC Criteria: December 9, 2008
• First Posted (ESTIMATE): December 10, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): December 20, 2012
• Last Update Submitted That Met QC Criteria: November 20, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: Candidiasis; Invasive Candidiasis; Candida; Candidemia; Fungal Infection; Neutropenia
• Additional Relevant MeSH Terms: Pathologic Processes; Systemic Inflammatory Response Syndrome; Inflammation; Hematologic Diseases; Bacterial Infections and Mycoses; Sepsis; Mycoses; Invasive Fungal Infections; Agranulocytosis; Leukopenia; Leukocyte Disorders; Infections; Candidiasis; Neutropenia; Fungemia; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antifungal Agents; Caspofungin; Anidulafungin
• Other Study ID Numbers: A8851021