Clinical trial NCT00106288: Micafungin Versus AmBisome in Invasive Candidiasis and Candidemia
Official title: A Multicenter, Double Blind, Comparative, Randomized Study to Evaluate the Efficacy and Safety of Micafungin (FK463) Versus Liposomal Amphotericin B (AmBisome) in the Treatment of Invasive Candidiasis and Candidemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Candidiasis
Keywords: Candidaemia
Micafungin
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2005-03-23
Enrollment: 637
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the efficacy and safety of micafungin (FK463) versus liposomal amphotericin B (AmBisome) in treating neutropenic and non-neutropenic patients with confirmed invasive candidiasis or candidemia. Enrollment will include adult and pediatric patients.

Detailed description: A phase III, multicenter, double-blind, comparative, parallel, randomized study. Enrollment will include adult and pediatric patients. The adult population is sized to test for non-inferiority. For the pediatric population, descriptive analyses are planned.

Eligibility criteria: Inclusion Criteria:

Patients either non-neutropenic with absolute neutrophil counts \>= 500 cells/mm3 or neutropenic with absolute neutrophil counts \< 500 cells/mm3 must have:

* Candidemia or invasive candidiasis,
* Confirmation and typical clinical signs and symptoms by fungal culture and/or histology,
* Positive culture obtained no more than four days prior to the first dose of study medication.

Exclusion Criteria:

* Patient is pregnant or nursing
* Patients with evidence of liver disease as defined by: a) SGOT/AST or SGPT/ALT \> 10 times the upper limit of normal (ULN); or b) Total bilirubin \> 5 times ULN.
* Patients whose sole diagnosis is oropharyngeal and/or esophageal candidiasis and/or with positive cultures of urine specimens, sputum specimens, bronchoalveolar-lavage specimens or samples from indwelling drains.
* Patients who have received prophylactic/empiric therapy with azoles or conventional amphotericin B for more than three days within one week prior to enrollment. Neutropenic patients, however, may have received prophylactic azoles without time restrictions.

Primary outcomes:
measure: Investigator's assessment of overall treatment success. Success is defined as clinical (complete or partial) and mycological (eradication or presumed eradication) response at the End of Therapy.
timeFrame: 6 and 12 weeks post treatment
Secondary outcomes:
measure: Clinical response (complete, partial, stabilization, progression) during the treatment period and the post-treatment period
timeFrame: During the 2 to 8 week treatment period and the 12 week post treatment followup period
measure: Mycological response (eradication, presumed eradication, persistence) during the treatment period and the post-treatment period
timeFrame: During the 2 to 8 week treatment period and the 12 week post treatment followup period
measure: Overall incidence of emergent and recurrent fungal infections at the End of Study
timeFrame: End of the 12 week post treatment followup peroid
measure: Independent Efficacy Review Committee's assessment of overall treatment success
timeFrame: Prior to database lock
measure: Peak change of estimated glomerular filtration rate during the treatment period compared to Baseline
timeFrame: During the 2 to 8 week treatment period
measure: Incidence of acute infusion related reactions as pre-defined
timeFrame: During the 2 to 8 week treatment period
measure: Patient survival at the End of Therapy and at the End of Study
timeFrame: End of the 2 to 8 week treatment period and end of the 12 week post treatment followup period
measure: Overall incidence of Adverse Events (AE)
timeFrame: Throughout study and post treatment followup period
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Orange
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Washington, DC
country: United States
state: District of Columbia
city: Jacksonville
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Hinsdale
country: United States
state: Illinois
city: Maywood
country: United States
state: Illinois
city: Kansas City
country: United States
state: Kansas
city: Lexington
country: United States
state: Kentucky
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Boston
country: United States
state: Massachusetts
city: Detroit
country: United States
state: Michigan
city: Minneapolis
country: United States
state: Minnesota
city: New York
country: United States
state: New York
city: New York
country: United States
state: New York
city: New York
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Valhalla
country: United States
state: New York
city: Durham
country: United States
state: North Carolina
city: Philadelphia
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Provo
country: United States
state: Utah
city: Calgary
country: Canada
state: Alberta
city: Vancouver
country: Canada
state: British Columbia
city: Winnipeg
country: Canada
state: Manitoba
city: Halifax
country: Canada
state: Nova Scotia
city: Hamilton
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Montreal
country: Canada
state: Quebec
city: Regina
country: Canada
state: Saskatchewan
city: Quebec
country: Canada
Study officials:
affiliation: Astellas Pharma Europe B.V.
name: Use Central Contact
role: STUDY_CHAIR
References:
citation: Kuse ER, Chetchotisakd P, da Cunha CA, Ruhnke M, Barrios C, Raghunadharao D, Sekhon JS, Freire A, Ramasubramanian V, Demeyer I, Nucci M, Leelarasamee A, Jacobs F, Decruyenaere J, Pittet D, Ullmann AJ, Ostrosky-Zeichner L, Lortholary O, Koblinger S, Diekmann-Berndt H, Cornely OA; Micafungin Invasive Candidiasis Working Group. Micafungin versus liposomal amphotericin B for candidaemia and invasive candidosis: a phase III randomised double-blind trial. Lancet. 2007 May 5;369(9572):1519-1527. doi: 10.1016/S0140-6736(07)60605-9.
citation: Queiroz-Telles F, Berezin E, Leverger G, Freire A, van der Vyver A, Chotpitayasunondh T, Konja J, Diekmann-Berndt H, Koblinger S, Groll AH, Arrieta A; Micafungin Invasive Candidiasis Study Group. Micafungin versus liposomal amphotericin B for pediatric patients with invasive candidiasis: substudy of a randomized double-blind trial. Pediatr Infect Dis J. 2008 Sep;27(9):820-6. doi: 10.1097/INF.0b013e31817275e6.
citation: Horn DL, Ostrosky-Zeichner L, Morris MI, Ullmann AJ, Wu C, Buell DN, Kovanda LL, Cornely OA. Factors related to survival and treatment success in invasive candidiasis or candidemia: a pooled analysis of two large, prospective, micafungin trials. Eur J Clin Microbiol Infect Dis. 2010 Feb;29(2):223-9. doi: 10.1007/s10096-009-0843-0. Epub 2009 Dec 15.
citation: Shorr AF, Wu C, Kothari S. Outcomes with micafungin in patients with candidaemia or invasive candidiasis due to Candida glabrata and Candida krusei. J Antimicrob Chemother. 2011 Feb;66(2):375-80. doi: 10.1093/jac/dkq446. Epub 2010 Dec 8.
citation: Dupont BF, Lortholary O, Ostrosky-Zeichner L, Stucker F, Yeldandi V. Treatment of candidemia and invasive candidiasis in the intensive care unit: post hoc analysis of a randomized, controlled trial comparing micafungin and liposomal amphotericin B. Crit Care. 2009;13(5):R159. doi: 10.1186/cc8117. Epub 2009 Oct 5.