Clinical trial NCT00548262: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Candidemia
Invasive Candidiasis
Keywords: Open-label
non-comparative study to evaluate short course of IV anidulafungin
followed by oral voriconazole
for tx of candidemia/invasive candidiasis.
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2007-10-23
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: Number of Participants for Global Response (Based on Clinical and Microbiological Success or Failure) at End of Treatment
timeFrame: End of Treatment (EOT) (up to Day 42)
Secondary outcomes:
measure: Number of Participants for Global Response (Based on Clinical and Microbiological Success or Failure)
timeFrame: End of Intravenous Treatment (EIVT) (up to Day 42), Week 2 Follow-up
measure: Number of Participants for Global Response Per Type of Candida Species Isolated at Baseline: EIVT
timeFrame: Baseline, EIVT (up to Day 42)
measure: Number of Participants for Global Response Per Type of Candida Species Isolated at Baseline: EOT
timeFrame: Baseline, EOT (up to Day 42)
measure: Number of Participants for Global Response Per Type of Candida Species Isolated at Baseline: Week 2 Follow-up
timeFrame: Baseline, Week 2 Follow-up
measure: Number of Participants for Global Response for Pre-specified Baseline Risk Factors Subgroups of Interest: EOT
timeFrame: Baseline, EOT (up to Day 42)
measure: Number of Participants for Global Response for Baseline Risk Factors for Candidemia and Invasive Candidiasis: EIVT
timeFrame: EIVT (up to Day 42)
measure: Number of Participants for Global Response for Baseline Risk Factors for Candidemia and Invasive Candidiasis: Week 2 Follow-up
timeFrame: Baseline, Week 2 Follow-up (F/U)
measure: Number of Participants for Global Response by Acute Physiological Assessment and Chronic Health Evaluation II (APACHE II) Score
timeFrame: EIVT (up to Day 42), EOT (up to Day 42), Week 2 Follow-up
measure: Number of Participants Per Survival Status (Alive or Dead) on Day 30
timeFrame: Day 30
measure: Number of Participants With Death Attributable (Yes or No) to Candidemia or Invasive Candidiasis
timeFrame: Baseline to Week 6 Follow-up
measure: Time to Negative Blood, Specimen, or Tissue Culture
timeFrame: Baseline to Week 2 Follow-up
measure: Duration of Exposure to Intravenous Anidulafungin Prior to Switch to Oral Voriconazole Treatment
timeFrame: Baseline to Day 42
measure: Length of Hospital Stay
timeFrame: Baseline to Week 6 Follow-up
measure: Length of Stay in Intensive Care Unit (ICU)
timeFrame: Baseline up to Week 6 Follow-up
measure: Change From Baseline in Vital Signs: Supine Blood Pressure
timeFrame: Baseline to Week 2 Follow-up
measure: Change From Baseline in Vital Signs: Supine Heart Rate
timeFrame: Baseline to Week 2 Follow-up
measure: Change From Baseline in Vital Signs: Weight
timeFrame: Baseline to Week 2 Follow-up
measure: Change From Baseline in Vital Signs: Temperature
timeFrame: Baseline to Week 2 Follow-up
measure: Change From Baseline in Vital Signs: Respiration Rate
timeFrame: Baseline to Week 2 Follow-up
measure: Change From Baseline in Chemistry Laboratory Test Data (Measured as mg/dL)
timeFrame: Baseline to Week 2 Follow-up
measure: Change From Baseline in Chemistry Laboratory Test Data (Measured as IU/L)
timeFrame: Baseline to Week 2 Follow-up
Other outcomes:
Locations:
city: Brasilia
country: Brazil
facility: Pfizer Investigational Site
state: DF
city: Curitiba
country: Brazil
facility: Pfizer Investigational Site
state: PR
city: Rio de Janeiro
country: Brazil
facility: Pfizer Investigational Site
state: RJ
city: Porto Alegre
country: Brazil
facility: Pfizer Investigational Site
state: RS
city: Porto Alegre
country: Brazil
facility: Pfizer Investigational Site
state: RS
city: Sao Jose do Rio Preto
country: Brazil
facility: Pfizer Investigational Site
state: SP
city: Independencia
country: Chile
facility: Pfizer Investigational Site
state: Santiago, RM
city: Bogota DC
country: Colombia
facility: Pfizer Investigational Site
state: Cundinamarca
city: Cali
country: Colombia
facility: Pfizer Investigational Site
state: Valle Del Cauca
city: Leon
country: Mexico
facility: Pfizer Investigational Site
state: Guanajuato
city: Guadalajara
country: Mexico
facility: Pfizer Investigational Site
state: Jalisco
city: San Luis Potosi
country: Mexico
facility: Pfizer Investigational Site
city: Panama
country: Panama
facility: Pfizer Investigational Site
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Sganga G, Wang M, Capparella MR, Tawadrous M, Yan JL, Aram JA, Montravers P. Evaluation of anidulafungin in the treatment of intra-abdominal candidiasis: a pooled analysis of patient-level data from 5 prospective studies. Eur J Clin Microbiol Infect Dis. 2019 Oct;38(10):1849-1856. doi: 10.1007/s10096-019-03617-9. Epub 2019 Jul 6.
citation: 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.
citation: 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.
citation: Nucci M, Colombo AL, Petti M, Magana M, Abreu P, Schlamm HT, Sanchez SP. An open-label study of anidulafungin for the treatment of candidaemia/invasive candidiasis in Latin America. Mycoses. 2014 Jan;57(1):12-8. doi: 10.1111/myc.12094. Epub 2013 May 26.