Isavuconazole (BAL8557) in the Treatment of Candidemia and Other Invasive Candida Infections
- Conditions
- MycosesCandidiasis, InvasiveCandidemia
- Interventions
- Registration Number
- NCT00413218
- Lead Sponsor
- Astellas Pharma Inc
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 450
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Isavuconazole (ISA) Isavuconazole Participants received 3 intravenous (IV) loading doses of 200 mg of isavuconazole on days 1 and 2, followed by an IV maintenance dose of 200 mg once daily from day 3 to day 56. On day 11 at the discretion of the investigator, non-neutropenic patients could switch from IV to oral therapy. Oral therapy consisted of 200 mg isavuconazole twice daily. Caspofungin (CAS)/Voriconazole Caspofungin Participants received 1 intravenous (IV) loading dose of 70 mg CAS on day 1, followed by an IV maintenance dose of 50 mg CAS from day 2 to day 56. On day 11 at the discretion of the investigator, non-neutropenic patients could switch from IV CAS to oral voriconazole comprising of a loading dose of 400 mg twice daily (BID) on the first day of oral therapy followed by standard dosing of 200 mg BID thereafter. Caspofungin (CAS)/Voriconazole Voriconazole Participants received 1 intravenous (IV) loading dose of 70 mg CAS on day 1, followed by an IV maintenance dose of 50 mg CAS from day 2 to day 56. On day 11 at the discretion of the investigator, non-neutropenic patients could switch from IV CAS to oral voriconazole comprising of a loading dose of 400 mg twice daily (BID) on the first day of oral therapy followed by standard dosing of 200 mg BID thereafter.
- Primary Outcome Measures
Name Time Method 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 End of Intravenous Treatment (EOIV) (Days 11-56) A Data Review Committee (DRC) was established from independent experts in the field of fungal infections to determine diagnosis and outcomes independently of the investigators and sponsor. Success was defined as clinical response (complete or partial) and mycological response (eradication or presumed eradication) without the use of alternative systemic antifungal therapy (AFT) within 48 hours after the last dose of IV study medication.
- Secondary Outcome Measures
Name Time Method 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 EOT (Day 56) and FU2 (6 weeks after end of treatment) A data review committee (DRC) was established from independent experts in the field of fungal infections to determine diagnosis and outcomes independently of the investigators and sponsor. Success was defined as clinical response (complete or partial) and mycological response (eradication or presumed eradication), without the use of alternative systemic antifungal therapy AFT within 48 hours after the last dose of IV study medication (for EOT analysis) or for continued treatment of the primary infection, or for recurrent or emergent infection by FU2, with no recurrent or emergent infection by FU2 (for FU2 analysis).
Percentage of Participants With Clinical Response of Success at EOIV, EOT, FU1 and FU2 as Determined by the Data Review Committee (DRC) EOIV (Days 11-56), EOT (Day 56), FU1 (2 weeks after end of treatment) and FU2 (6 weeks after end of treatment) A data review committee (DRC) was established from independent experts in the field of fungal infections to determine diagnosis and outcomes independently of the investigators and sponsor. Success was defined as clinical response (complete or partial).
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) End of Treatment (EOT) (Day 56) and FU1 (2 weeks after end of treatment) A data review committee (DRC) was established from independent experts in the field of fungal infections to determine diagnosis and outcomes independently of the investigators and sponsor. Success was defined as clinical response (complete or partial) and mycological response (eradication or presumed eradication), without the use of alternative systemic AFT within 48 hours after the last dose of IV study medication.
Percentage of Participants With Mycological Response of Success at Day 7 and EOT as Determined by The Investigator Day 7 and EOT (Day 56) Success was defined as mycological response (eradication or presumed eradication).
Percentage of Participants With Mycological Response of Success at EOIV, EOT, FU1 and FU2 as Determined by the Data Review Committee (DRC) EOIV (Days 11-56), EOT (Day 56), FU1 (2 weeks after end of treatment) and FU2 (6 weeks after end of treatment) A data review committee (DRC) was established from independent experts in the field of fungal infections to determine diagnosis and outcomes independently of the investigators and sponsor. Success was defined as mycological response (Eradication or Presumed Eradication).
Percentage of Participants With Clinical Response of Success at Day 7 and EOT as Determined by The Investigator Day 7 and EOT (Day 56) Investigators defined clinical response as success if participants exhibited complete or partial clinical response after evaluation of clinical signs and symptoms.
All-Cause Mortality (ACM) at Day 14 and Day 56 Day 14 and Day 56 All-cause mortality is represented as the percentage of participants who died on or before the analysis day. Participants who were lost to follow-up (i.e., unknown survival status) before the analysis day were counted as death. All-cause mortality was examined on Day 14 and Day 56.
Time to First Confirmed Negative Culture Day 1 up to FU1 (2 weeks after EOT (Day 56)) The first confirmed negative blood culture was defined as the first negative blood culture on or after first dose followed by a second negative blood culture at least 24 hours apart without any positive blood cultures in between. A participant without a confirmed negative blood culture was censored on the participant's last visit day. This endpoint was analyzed for mITT participants with candidemia only using the Kaplan-Meier method. Only participants with at least one positive blood culture on or prior to first dose and the culture not resolved prior to first dose were included in this analysis
Trial Locations
- Locations (113)
Idaho Falls Infectious Diseases PLLC
🇺🇸Idaho Falls, Idaho, United States
Somero Research Corporation
🇺🇸Palm Desert, California, United States
Loyola University Hospital
🇺🇸Maywood, Illinois, United States
Springfield Clinic LLP
🇺🇸Springfield, Illinois, United States
Jersey Shore University Medical Center
🇺🇸Neptune, New Jersey, United States
Hospital General de Agudos Dr. Cosme Argerich
🇦🇷La Boca, Argentina
Fremantle Hospital
🇦🇺Fremantle, Australia
Mater Adult Hospital
🇦🇺South Brisbane, Australia
Westmead Hospital
🇦🇺Westmead, Australia
Princess Alexandra Hospital
🇦🇺Woolloongabba, Australia
Hospital Universitario de Santa Maria
🇧🇷Santa Maria, Brazil
Hospital Dr. Hernan Henriquez Aravena
🇨🇱Temuco, Chile
Universitaetsklinik Leipzig
🇩🇪Leipzig, Germany
Universitaetsklinikum Leipzig
🇩🇪Luebeck, Germany
Rabin MC
🇮🇱Petah, Israel
Ente Ospedaliero Ospedeli Galliera
🇮🇹Genova, Italy
AUB Medical Center
🇱🇧Beirut, Lebanon
Hospital Ampang
🇲🇾Ampang, Malaysia
Pusat Perubatan Universiti Kebangsaan Malaysia
🇲🇾Kuala Lumpur, Malaysia
Auckland City Hospital
🇳🇿Auckland, New Zealand
Philippine General Hospital
🇵ðŸ‡Manila, Philippines
Singapore General Hospital - Parent
🇸🇬Singapore, Singapore
Hospital del Mar
🇪🇸Barcelona, Spain
Siriraj Hospital
🇹ðŸ‡Bangkoknoi, Thailand
Maharat Nakhon Ratchasima Hospital
🇹ðŸ‡Muang, Thailand
Srinagarind Hospital
🇹ðŸ‡Muang, Thailand
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
University of Maryland School of Medicine
🇺🇸Baltimore, Maryland, United States
UMASS Memorial Medical Center
🇺🇸Worcester, Massachusetts, United States
Mercury Street Medical Group
🇺🇸Butte, Montana, United States
Instituto Medico Especializado Alexander Fleming
🇦🇷Ciudad Autonoma, Argentina
Hospital Britanico de Buenos Aires
🇦🇷Capital Federal, Argentina
Hospital General de Agudos Dr. Carlos G. Durand
🇦🇷Capital Federal, Argentina
Hospital Italiano de Buenos Aires
🇦🇷Ciudad Autonoma, Argentina
Institut Jules Bordet
🇧🇪Brussels, Belgium
Universitair Ziekenhuis Brussel
🇧🇪Brussels, Belgium
ULB Hôpital Erasme
🇧🇪Bruxelles, Belgium
Universitair Ziekenhuis Gent
🇧🇪Gent, Belgium
Universitaire Ziekenhuizen Leuven
🇧🇪Leuven, Belgium
Irmandade da Santa Casa de Misericordia de Porto Alegre
🇧🇷Porto Alegre, Brazil
Hospital Felicio Rocho
🇧🇷Belo Horizonte, Brazil
Hospital das Clinicas da Universidade Federal de Minas Gerai
🇧🇷Belo Horizonte, Brazil
Santa Casa de Misericordia de Belo Horizonte
🇧🇷Belo Horizonte, Brazil
Hospital das Clinicas da UFPR
🇧🇷Curitiba, Brazil
Hospital Nossa Senhora das Gracas
🇧🇷Curitiba, Brazil
Hospital Sao Lucas - PUCRS
🇧🇷Porto Alegre, Brazil
Hospital Universitario Clementino Fraga Filho
🇧🇷Rio de Janeiro, Brazil
Hôpital Maisonneuve - Rosemont
🇨🇦Montreal, Quebec, Canada
Hospital del Salvador
🇨🇱Santiago, Chile
Hamilton Health Sciences - Henderson Site
🇨🇦Hamilton, Ontario, Canada
Universidade Federal de Sao Paulo - UNIFESP
🇧🇷São Paulo, Brazil
University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
Hôpital de Brabois Adultes
🇫🇷Vandoeuvre les Nancy, France
Queen's University
🇨🇦Kingston, Ontario, Canada
University Health Network - Toronto General Hospital
🇨🇦Toronto, Ontario, Canada
Hospital Dr. Sotero del Rio
🇨🇱Puente Alto Santiago, Chile
West China Hospital of Sichuan University
🇨🇳Chengdu, China
Hôpital Hautepierre
🇫🇷Strasbourg, France
The Ottawa Hospital - General Campus
🇨🇦Ottawa, Ontario, Canada
Huashan Hospital Fudan University
🇨🇳Shanghai, China
Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum
ðŸ‡ðŸ‡ºDebrecen, Hungary
Charite Campus Mitte
🇩🇪Berlin, Germany
Universitaetsklinikum Freiburg
🇩🇪Freiburg, Germany
Klinikum St. Georg
🇩🇪Leipzig, Germany
Universitaet Koeln
🇩🇪Koeln, Germany
Universitaetsklinikum Wuerzburg
🇩🇪Wuerzburg, Germany
Petz Aladar Megyei Oktato Korhaz
ðŸ‡ðŸ‡ºGyör, Hungary
Kasturba Medical College and Hospital
🇮🇳Mangalore, Karna, India
Kasturba Medical College K. M. C. Hospital
🇮🇳Manipal, Karna, India
Amrita Institute Of Medical Science
🇮🇳Cochin, Kerala, India
Deenanath Mangeshkar Hospital and Research Centre
🇮🇳Pune, Mahara, India
Apollo Hospitals Educational & Research Foundation
🇮🇳Chennai, India
Nizam's Institute of Medical Sciences
🇮🇳Hyderabad, India
Rambam Health Care Campus
🇮🇱Haifa, Israel
Chaim Sheba Medical Center
🇮🇱Ramat Gan, Israel
AMRI Hospital
🇮🇳Kolkata, India
Christian Medical College & Hospital
🇮🇳Vellore Tamilnadu, India
Ha Emek Medical Center
🇮🇱Afula, Israel
Hadassah Universtiy Hospital - Ein Kerem
🇮🇱Jerusalem, Israel
Instituto Nacional de Ciencias Medicas y Nutricion Salvador
🇲🇽Mexico, Mexico
Wolfson Medical Center
🇮🇱Holon, Israel
Sapir Medical Center, Meir Hospital
🇮🇱Kfar-Saba, Israel
Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Ma
🇮🇹Bologna, Italy
Sourasky MC Ichilov Hospital Tel Aviv
🇮🇱Tel Aviv, Israel
Azienda Ospedaliera Spedali Civili di Brescia
🇮🇹Brescia, Italy
Azienda Ospedaliero Universitaria San Martino
🇮🇹Genova, Italy
Azienda Ospedaliera di Verona-Ospedale Civile Maggiore
🇮🇹Verona, Italy
Rafik Hariri Uni Hospital
🇱🇧Beirut, Lebanon
Hospital Civil de Guadalajara Dr Juan I Menchaca
🇲🇽Guadalajara, Mexico
De La Salle Health Sciences Institute- DLSUMC
🇵ðŸ‡Cavite City, Philippines
State Institution "Hematology Research Center" RAMS
🇷🇺Moscow, Russian Federation
Hospital Civil de Guadalajara Fray Antonio Alcalde
🇲🇽Guadalajara, Mexico
Hospital Universitario Dr Jose Eleuterio Gonzalez
🇲🇽Monterrey, Mexico
S.I. Russian Oncological Research Center n.a. N.N. Blokhin
🇷🇺Moscow, Russian Federation
Waikato Urology Research Ltd
🇳🇿Hamilton, New Zealand
Hôpitaux Universitaires de Genève - HUG
🇨ðŸ‡Geneva, Switzerland
Universitaetsspital Zuerich
🇨ðŸ‡Zurich, Switzerland
National Neuroscience Institute
🇸🇬Singapore, Singapore
Unitas Hospital
🇿🇦Lyttelton Centurion, South Africa
Ramathibodi Hospital
🇹ðŸ‡Ratchathewi, Thailand
Songklanagarind Hospital
🇹ðŸ‡Hat Yai, Thailand
Maharaj Nakorn Chiang Mai Hospital
🇹ðŸ‡Muang, Thailand
Temple University Health Sciences
🇺🇸Philadelphia, Pennsylvania, United States
Regional Infection Diseases Infusion Center Inc.
🇺🇸Lima, Ohio, United States
Metro Centre for Respiratory Diseases
🇮🇳Noida, Delhi, India
Max Super Speciality Hospital
🇮🇳New Delhi, Delhi, India
New York Presbyterian Hospital
🇺🇸New York, New York, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
University of California Davis Health System
🇺🇸Sacramento, California, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
University of California at San Francisco
🇺🇸San Francisco, California, United States
Infectious Disease of Indiana
🇺🇸Indianapolis, Indiana, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States