Clinical trial NCT00413218: Isavuconazole (BAL8557) in the Treatment of Candidemia and Other Invasive Candida Infections
Official title: A Phase III, Double-blind, Randomized Study to Evaluate the Safety and Efficacy of BAL8557 Versus a Caspofungin Followed by Voriconazole Regimen in the Treatment of Candidemia and Other Invasive Candida Infections
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Candidiasis, Invasive
Candidemia
Mycoses
Keywords: Invasive Candida infections
BAL8557
ASP9766
Isavuconazole
Candidemia
Candidemia and other invasive candida infections
Phase III study
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
Collaborators: name: Basilea Pharmaceutica
First posted: 2006-12-19
Enrollment: 450
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to compare the safety and efficacy of isavuconazole versus caspofungin followed by voriconazole in the treatment of candidemia and other invasive Candida infections.

Detailed description: Candida infections, representing approximately 80% of all major systemic fungal infections, are the fourth most common cause of nosocomial bloodstream infections, with a mortality rate of 40%. Isavuconazole is not yet approved for the treatment of fungal infections. This study investigates the efficacy and safety of intravenous and oral isavuconazole. Patients are randomized to isavuconazole and the reference regimen. Patients with a positive blood- or deep tissue culture of candida fungi can be included.

Eligibility criteria: Inclusion Criteria:

* Patients with candidemia or with an invasive Candida infection
* Presence of fever, hypothermia or other appropriate local sign of infection
* Female patients must be non-lactating and at no risk of pregnancy

Exclusion Criteria:

* Patients with a sole diagnosis of mucocutaneous candidiasis, i.e. oropharyngeal, esophageal or genital candidiasis; or candidal lower urinary tract infection or Candida isolated solely from respiratory tract specimens
* Patients with candidemia who failed a previous antifungal therapy for the same infection
* Patients previously enrolled in a phase III study with isavuconazole
* Patients with a body weight \<40kg

Primary outcomes:
measure: Percentage of Participants With Overall Response of Success at the End of Intravenous Therapy (EOIV) as Determined by the Data Review Committee (DRC) Based on the Assessments of Clinical and Mycological Responses as Well as Alternative Systemic AFT Use
timeFrame: End of Intravenous Treatment (EOIV) (Days 11-56)
Secondary outcomes:
measure: Percentage of Participants With Overall Response of Success at Follow Up Visit 1 (FU1-2 Weeks After End of Treatment (EOT)) as Determined by the DRC Based on the Assessments of Clinical, Mycological Responses and Antifungal Therapy (AFT)
timeFrame: End of Treatment (EOT) (Day 56) and FU1 (2 weeks after end of treatment)
measure: Percentage of Participants With Overall Response of Success at EOT and Follow Up Visit 2 (FU2) as Determined by the DRC Based on the Assessments of Clinical and Mycological Responses as Well as Alternative Systemic AFT Use at EOT and FU2
timeFrame: EOT (Day 56) and FU2 (6 weeks after end of treatment)
measure: Percentage of Participants With Clinical Response of Success at EOIV, EOT, FU1 and FU2 as Determined by the Data Review Committee (DRC)
timeFrame: EOIV (Days 11-56), EOT (Day 56), FU1 (2 weeks after end of treatment) and FU2 (6 weeks after end of treatment)
measure: Percentage of Participants With Mycological Response of Success at EOIV, EOT, FU1 and FU2 as Determined by the Data Review Committee (DRC)
timeFrame: EOIV (Days 11-56), EOT (Day 56), FU1 (2 weeks after end of treatment) and FU2 (6 weeks after end of treatment)
measure: Percentage of Participants With Mycological Response of Success at Day 7 and EOT as Determined by The Investigator
timeFrame: Day 7 and EOT (Day 56)
measure: Percentage of Participants With Clinical Response of Success at Day 7 and EOT as Determined by The Investigator
timeFrame: Day 7 and EOT (Day 56)
measure: All-Cause Mortality (ACM) at Day 14 and Day 56
timeFrame: Day 14 and Day 56
measure: Time to First Confirmed Negative Culture
timeFrame: Day 1 up to FU1 (2 weeks after EOT (Day 56))
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Palm Desert
country: United States
facility: Somero Research Corporation
state: California
city: Sacramento
country: United States
facility: University of California Davis Health System
state: California
city: San Francisco
country: United States
facility: University of California at San Francisco
state: California
city: Idaho Falls
country: United States
facility: Idaho Falls Infectious Diseases PLLC
state: Idaho
city: Maywood
country: United States
facility: Loyola University Hospital
state: Illinois
city: Springfield
country: United States
facility: Springfield Clinic LLP
state: Illinois
city: Indianapolis
country: United States
facility: Infectious Disease of Indiana
state: Indiana
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland School of Medicine
state: Maryland
city: Worcester
country: United States
facility: UMASS Memorial Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Butte
country: United States
facility: Mercury Street Medical Group
state: Montana
city: Neptune
country: United States
facility: Jersey Shore University Medical Center
state: New Jersey
city: New York
country: United States
facility: New York Presbyterian Hospital
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Lima
country: United States
facility: Regional Infection Diseases Infusion Center Inc.
state: Ohio
city: Philadelphia
country: United States
facility: Temple University Health Sciences
state: Pennsylvania
city: Capital Federal
country: Argentina
facility: Hospital Britanico de Buenos Aires
city: Capital Federal
country: Argentina
facility: Hospital General de Agudos Dr. Carlos G. Durand
city: Ciudad Autonoma
country: Argentina
facility: Hospital Italiano de Buenos Aires
city: Ciudad Autonoma
country: Argentina
facility: Instituto Medico Especializado Alexander Fleming
city: La Boca
country: Argentina
facility: Hospital General de Agudos Dr. Cosme Argerich
city: Fremantle
country: Australia
facility: Fremantle Hospital
city: South Brisbane
country: Australia
facility: Mater Adult Hospital
city: Westmead
country: Australia
facility: Westmead Hospital
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Brussels
country: Belgium
facility: Universitair Ziekenhuis Brussel
city: Bruxelles
country: Belgium
facility: ULB Hôpital Erasme
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven
city: Belo Horizonte
country: Brazil
facility: Hospital Felicio Rocho
city: Belo Horizonte
country: Brazil
facility: Hospital das Clinicas da Universidade Federal de Minas Gerai
city: Belo Horizonte
country: Brazil
facility: Santa Casa de Misericordia de Belo Horizonte
city: Curitiba
country: Brazil
facility: Hospital das Clinicas da UFPR
city: Curitiba
country: Brazil
facility: Hospital Nossa Senhora das Gracas
city: Porto Alegre
country: Brazil
facility: Hospital Sao Lucas - PUCRS
city: Porto Alegre
country: Brazil
facility: Irmandade da Santa Casa de Misericordia de Porto Alegre
city: Rio de Janeiro
country: Brazil
facility: Hospital Universitario Clementino Fraga Filho
city: Santa Maria
country: Brazil
facility: Hospital Universitario de Santa Maria
city: São Paulo
country: Brazil
facility: Universidade Federal de Sao Paulo - UNIFESP
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Hamilton
country: Canada
facility: Hamilton Health Sciences - Henderson Site
state: Ontario
city: Kingston
country: Canada
facility: Queen's University
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital - General Campus
state: Ontario
city: Toronto
country: Canada
facility: University Health Network - Toronto General Hospital
state: Ontario
city: Montreal
country: Canada
facility: Hôpital Maisonneuve - Rosemont
state: Quebec
city: Puente Alto Santiago
country: Chile
facility: Hospital Dr. Sotero del Rio
city: Santiago
country: Chile
facility: Hospital del Salvador
city: Temuco
country: Chile
facility: Hospital Dr. Hernan Henriquez Aravena
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
city: Shanghai
country: China
facility: Huashan Hospital Fudan University
city: Strasbourg
country: France
facility: Hôpital Hautepierre
city: Vandoeuvre les Nancy
country: France
facility: Hôpital de Brabois Adultes
city: Berlin
country: Germany
facility: Charite Campus Mitte
city: Freiburg
country: Germany
facility: Universitaetsklinikum Freiburg
city: Koeln
country: Germany
facility: Universitaet Koeln
city: Leipzig
country: Germany
facility: Klinikum St. Georg
city: Leipzig
country: Germany
facility: Universitaetsklinik Leipzig
city: Luebeck
country: Germany
facility: Universitaetsklinikum Leipzig
city: Wuerzburg
country: Germany
facility: Universitaetsklinikum Wuerzburg
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum
city: Györ
country: Hungary
facility: Petz Aladar Megyei Oktato Korhaz
city: New Delhi
country: India
facility: Max Super Speciality Hospital
state: Delhi
city: Noida
country: India
facility: Metro Centre for Respiratory Diseases
state: Delhi
city: Mangalore
country: India
facility: Kasturba Medical College and Hospital
state: Karna
city: Manipal
country: India
facility: Kasturba Medical College K. M. C. Hospital
state: Karna
city: Cochin
country: India
facility: Amrita Institute Of Medical Science
state: Kerala
city: Pune
country: India
facility: Deenanath Mangeshkar Hospital and Research Centre
state: Mahara
city: Chennai
country: India
facility: Apollo Hospitals Educational & Research Foundation
city: Hyderabad
country: India
facility: Nizam's Institute of Medical Sciences
city: Kolkata
country: India
facility: AMRI Hospital
city: Vellore Tamilnadu
country: India
facility: Christian Medical College & Hospital
city: Afula
country: Israel
facility: Ha Emek Medical Center
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Holon
country: Israel
facility: Wolfson Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Universtiy Hospital - Ein Kerem
city: Kfar-Saba
country: Israel
facility: Sapir Medical Center, Meir Hospital
city: Petah
country: Israel
facility: Rabin MC
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Sourasky MC Ichilov Hospital Tel Aviv
city: Bologna
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Ma
city: Brescia
country: Italy
facility: Azienda Ospedaliera Spedali Civili di Brescia
city: Genova
country: Italy
facility: Ente Ospedaliero Ospedeli Galliera
city: Genova
country: Italy
facility: Azienda Ospedaliero Universitaria San Martino
city: Verona
country: Italy
facility: Azienda Ospedaliera di Verona-Ospedale Civile Maggiore
city: Beirut
country: Lebanon
facility: AUB Medical Center
city: Beirut
country: Lebanon
facility: Rafik Hariri Uni Hospital
city: Ampang
country: Malaysia
facility: Hospital Ampang
city: Kuala Lumpur
country: Malaysia
facility: Pusat Perubatan Universiti Kebangsaan Malaysia
city: Guadalajara
country: Mexico
facility: Hospital Civil de Guadalajara Fray Antonio Alcalde
city: Guadalajara
country: Mexico
facility: Hospital Civil de Guadalajara Dr Juan I Menchaca
city: Mexico
country: Mexico
facility: Instituto Nacional de Ciencias Medicas y Nutricion Salvador
city: Monterrey
country: Mexico
facility: Hospital Universitario Dr Jose Eleuterio Gonzalez
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Hamilton
country: New Zealand
facility: Waikato Urology Research Ltd
city: Cavite City
country: Philippines
facility: De La Salle Health Sciences Institute- DLSUMC
city: Manila
country: Philippines
facility: Philippine General Hospital
city: Moscow
country: Russian Federation
facility: S.I. Russian Oncological Research Center n.a. N.N. Blokhin
city: Moscow
country: Russian Federation
facility: State Institution "Hematology Research Center" RAMS
city: Singapore
country: Singapore
facility: Singapore General Hospital - Parent
city: Singapore
country: Singapore
facility: National Neuroscience Institute
city: Lyttelton Centurion
country: South Africa
facility: Unitas Hospital
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Geneva
country: Switzerland
facility: Hôpitaux Universitaires de Genève - HUG
city: Zurich
country: Switzerland
facility: Universitaetsspital Zuerich
city: Bangkoknoi
country: Thailand
facility: Siriraj Hospital
city: Hat Yai
country: Thailand
facility: Songklanagarind Hospital
city: Muang
country: Thailand
facility: Maharat Nakhon Ratchasima Hospital
city: Muang
country: Thailand
facility: Srinagarind Hospital
city: Muang
country: Thailand
facility: Maharaj Nakorn Chiang Mai Hospital
city: Ratchathewi
country: Thailand
facility: Ramathibodi Hospital
Study officials:
affiliation: Astellas Pharma Global Development
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Kullberg BJ, Viscoli C, Pappas PG, Vazquez J, Ostrosky-Zeichner L, Rotstein C, Sobel JD, Herbrecht R, Rahav G, Jaruratanasirikul S, Chetchotisakd P, Van Wijngaerden E, De Waele J, Lademacher C, Engelhardt M, Kovanda L, Croos-Dabrera R, Fredericks C, Thompson GR. Isavuconazole Versus Caspofungin in the Treatment of Candidemia and Other Invasive Candida Infections: The ACTIVE Trial. Clin Infect Dis. 2019 May 30;68(12):1981-1989. doi: 10.1093/cid/ciy827.
citation: McCormack PL. Isavuconazonium: first global approval. Drugs. 2015 May;75(7):817-22. doi: 10.1007/s40265-015-0398-6.