Isavuconazole in the Treatment of Renally Impaired Aspergillosis and Rare Fungi
- Registration Number
- NCT00634049
- Lead Sponsor
- Astellas Pharma Inc
- Brief Summary
The purpose of this study is to investigate the efficacy and safety of isavuconazole in the treatment of renally impaired participants with invasive fungal infections caused by Aspergillus and participants with invasive fungal disease caused by rare fungi.
- Detailed Description
Acute invasive fungal infections caused by aspergillus, rare moulds, yeasts or dimorphic fungi are life threatening diseases. Early treatment with highly effective anti-fungals reduces mortality. This study investigates the safety and efficacy of isavuconazole in participants with aspergillosis and renal impairment, and in participants suffering from invasive infections from rare fungi.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 149
•Participants meeting EORTC/MSG (European Organization for the Research and Treatment of Cancer/Mycoses Study Group) definition of proven or culture positive probable IFD (invasive fungal disease) caused by rare moulds, yeasts, or dimorphic fungi (i.e. fungal pathogens other than Aspergillus fumigatus or Candida species) whether renally impaired or not (including dialysis) who require primary therapy for their IFD at the time of enrollment.
OR
•Participants who had proven or probable zygomycosis, whether renally impaired or not (including dialysis), who require primary therapy. Zygomycosis must be documented by culture or histology / cytology.
OR
•Participants meeting EORTC/MSG definition of proven or culture positive probable IFD caused by rare moulds, yeasts, or dimorphic fungi (i.e., fungal pathogens other than Aspergillus fumigatus or Candida species), whether RI or not (including dialysis), who were refractory to current treatment defined as,
- Clear documentation of progression of disease. Note: radiological progression only in association with white blood cell (WBC) count recovery was not acceptable.
- Failure to improve clinically despite receiving at least 7 days of standard antifungal regimen. Prior to enrolling patients who fell into this category, the Medical Monitor was contacted for approval.
OR
• Participants meeting EORTC/MSG definition of proven or culture positive probable IFD caused by rare moulds, yeasts, or dimorphic fungi (i.e., fungal pathogens other than Aspergillus fumigatus or Candida species), whether RI or not (including dialysis), who were intolerant to current treatment for example:
- Doubling of serum creatinine value to higher than the upper limit of normal (ULN) within 48 hours.
- Serum creatinine > 2.0 mg/mL and current treatment with polyene or IV voriconazole.
- Other significant drug-related adverse reaction(s) to the current antifungal agent, resulting in discontinuation of the treatment, e.g., persistence of visual disturbance, allergic reaction, phototoxicity or severe infusion reaction (hypertensive crisis, severe chills or shock).
- Documented inability to achieve adequate blood levels of posaconazole, voriconazole or itraconazole.
- A known condition of the participants that may jeopardize adherence to the protocol requirements
- Participants who are unlikely to survive 30 days
- Participants with a body weight < 40 kg
- Women who are pregnant or breastfeeding
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Isavuconazole isavuconazole Administration of isavuconazole 3 times a day in the vein (IV) or oral as a capsule for 2 days followed by daily administration of isavuconazole (IV) or oral
- Primary Outcome Measures
Name Time Method Crude Success Rate of Overall Outcome of Treatment Evaluated by the Data Review Committee (DRC) at Day 42, 84 and End of Treatment (EOT). Day 42, 84 and End of Treatment (EOT [Day 180]) The DRC assessed overall response based on individual clinical, mycological and radiological response assessments. Overall response outcomes were described as Success (complete or partial). Complete success was defined as a resolution of all clinical symptoms and physical findings associated with IFD. Partial success was defined as a resolution of at least some clinical symptoms and physical findings associated with IFD End of treatment (EOT) is the last day of study drug administration, with an estimated duration up to 180 days.
- Secondary Outcome Measures
Name Time Method Crude Success Rate of Clinical Response to Treatment Evaluated by the Data Review Committee (DRC) at Day 42, 84 and EOT Day 42, 84 and End of Treatment (EOT [Day 180]) The DRC evaluated clinical response to treatment at day 42, day 84 and EOT. Clinical response outcomes were described as Success \[Resolution of all attributable clinical symptoms and physical findings and Partial resolution of attributable clinical symptoms and physical findings\]. End of treatment (EOT) is the last day of study drug administration, with an estimated duration up to 180 days.
Crude Success Rate of Mycological Response to Treatment Evaluated by the Data Review Committee (DRC) at Day 42, 84 and EOT Day 42, 84 and End of Treatment (EOT [Day 180]) The DRC evaluated mycological response to treatment at day 42, day 84 and EOT. Mycological response outcomes were described as Success \[Eradication and Presumed eradication\]. End of treatment (EOT) is the last day of study drug administration, with an estimated duration up to 180 days.
Crude Success Rate of Radiological Response to Treatment Evaluated by the Data Review Committee (DRC) at Day 42, 84 and EOT Day 42, 84 and End of Treatment (EOT [Day 180]) The DRC evaluated radiological response to treatment at at day 42, day 84 and EOT. Radiological response outcomes were described as Success \[Improvement of at least 25% from baseline for invasive aspergillosis and other filamentous mold infections\], \[Improvement of at least 50% from baseline for invasive aspergillosis and other filamentous mold infections\]; and \[Improvement of at least 25% from baseline if EOT occurs prior to day 42 and at least 50% improvement from baseline if EOT occurs after day 42 for invasive aspergillosis and other filamentous mold infections\]. End of treatment (EOT) is the last day of study drug administration, with an estimated duration up to 180 days.
Crude Success Rate of Clinical Response to Treatment Evaluated by the Investigator at Day 42, Day 84 and EOT Day 42, Day 84 and End of Treatment (EOT [Day 180]) The Investigator evaluated clinical response to treatment at day 42, day 84 and EOT. Clinical response outcomes were described as Success \[Resolution of all attributable clinical symptoms and physical findings\] and \[Resolution of some attributable clinical symptoms and physical findings\]. End of treatment (EOT) is the last day of study drug administration, with an estimated duration up to 180 days.
Crude Success Rate of Mycological Response to Treatment Evaluated by the Investigator at Day 42, Day 84 and EOT Day 42, Day 84 and End of Treatment (EOT [Day 180]) The Investigator evaluated mycological response to treatment at day 42, day 84 and EOT. Mycological response outcomes were described as Success \[Eradication,Presumed eradication\]. End of treatment (EOT) is the last day of study drug administration, with an estimated duration up to 180 days.
Crude Success Rate of Radiological Response to Treatment Evaluated by the Investigator at Day 42, Day 84 and EOT Day 42, Day 84 and End of Treatment (EOT [Day 180]) The Investigator evaluated radiological response to treatment at day 42, day 84 and EOT. Radiological response outcomes were described as Success \[≥ 90% improvement,≥ 50% to \< 90% improvement and ≥ 25% to \< 50% improvement (for day 42 and EOT, if EOT occurs prior to day 42)\]. End of treatment (EOT) is the last day of study drug administration, with an estimated duration up to 180 days.
All-cause Mortality Through Day 42 and Day 84 Baseline to End of Treatment (EOT [Day 180]) All-cause Mortality was assessed through Day 42 and Day 84 and summarized for ITT population End of treatment (EOT) is the last day of study drug administration, with an estimated duration up to 180 days.
Safety - Overall Number of TEAEs From the first study drug administration until 28 days after the last dose of study drug A Treatment Emergent Adverse Events (TEAE) is any adverse event that starts after the first administration of study drug until 28 days after the last dose of study drug.
Trial Locations
- Locations (96)
UMASS Memorial Medical Center
🇺🇸Worcester, Massachusetts, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Upstate Infectious Diseases Association LLP
🇺🇸Albany, New York, United States
Instituto Medico Especializado Alexander Fleming
🇦🇷Ciudad Autonoma, Argentina
Hospital Nuestra Senora de la Misericordia
🇦🇷Cordoba, Argentina
Hospital San Roque
🇦🇷Cordoba, Argentina
Centro Polivalente de Asistencia e Investigación Clínica - CER San Juan
🇦🇷San Juan, Argentina
Institut Jules Bordet
🇧🇪Brussels, Belgium
Erasme Hospital
🇧🇪Bruxelles, Belgium
Universitaire Ziekenhuizen Leuven
🇧🇪Leuven, Belgium
Hôpital Maisonneuve - Rosemont
🇨🇦Montréal, Quebec, Canada
National Cancer Institute
🇪🇬Cairo, Egypt
Hospital Universitario Dr Jose Eleuterio Gonzalez
🇲🇽Monterrey, Mexico
Ramathibodi Hospital
🇹🇭Ratchathewi, Thailand
University of California Davis Health System
🇺🇸Sacramento, California, United States
Emory Hospital
🇺🇸Atlanta, Georgia, United States
Temple University Health Sciences
🇺🇸Philadelphia, Pennsylvania, United States
Hamilton Health Sciences - Henderson Site
🇨🇦Hamilton, Ontario, Canada
Hospital Professor Edmundo Vasconcelos
🇧🇷São Paulo, Brazil
University of Chicago, Division of Infectious Diseases
🇺🇸Chicago, Illinois, United States
Institut Paoli Calmette - Marseille
🇫🇷Marseille Cedex 9, France
Hôpital de Brabois Adultes
🇫🇷Vandoeuvre les Nancy, France
Stanford University Hospital
🇺🇸Stanford, California, United States
Mater Medical Centre
🇦🇺South Brisbane, Australia
Indiana BMT
🇺🇸Beech Grove, Indiana, United States
Regional Infection Diseases Infusion Center Inc.
🇺🇸Lima, Ohio, United States
City Of Hope National Medical Center
🇺🇸Duarte, California, United States
Hospital das Clinicas da UFPR
🇧🇷Curitiba, Brazil
Hospital de Clinicas da FMUSP - Ribeirao Preto
🇧🇷Ribeirao Preto, Brazil
Hospital Universitario de Santa Maria
🇧🇷Santa Maria, Brazil
Medanta Medicity Hospital
🇮🇳Gurgaon, Haryan, India
Universitair Ziekenhuis Gent
🇧🇪Gent, Belgium
Tata Memorial Hopital, Department of Anesthesia
🇮🇳Mumbai, Mahara, India
Nasser Institute
🇪🇬Cairo, Egypt
Santa Casa de Misericordia de Belo Horizonte
🇧🇷Belo Horizonte, Brazil
Hospital Felicio Rocho
🇧🇷Belo Horizonte, Brazil
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
University of Pittsburgh Medical Center Health System
🇺🇸Pittsburgh, Pennsylvania, United States
Hospital Italiano de Buenos Aires
🇦🇷Ciudad Autonoma, Argentina
The Ottawa Hospital - General Campus
🇨🇦Ottawa, Ontario, Canada
Hospital Universitario Clementino Fraga Filho
🇧🇷Rio de Janeiro, Brazil
Alexandria University Hospital
🇪🇬Alexandria, Egypt
Maharaj Nakorn Chiang Mai Hospital
🇹🇭Muang, Thailand
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
California Pacific Medical Center
🇺🇸San Francisco, California, United States
Infectious Disease of Indiana
🇺🇸Indianapolis, Indiana, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Fred Hutchinson Cancer Research Center, Clinical Research
🇺🇸Seattle, Washington, United States
Rabin MC
🇮🇱Petah Tikva, Israel
Chaim Sheba Medical Center
🇮🇱Ramat-Gan, Israel
Soonchunhyang University Bucheon Hospital
🇰🇷Buchon-si, Korea, Republic of
Rambam Health Care Campus
🇮🇱Haifa, Israel
University of California at San Francisco
🇺🇸San Francisco, California, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
University Of Colorado Health Sciences Center
🇺🇸Aurora, Colorado, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Brigham & Womens Hospital
🇺🇸Boston, Massachusetts, United States
Wayne State University School of Medicine
🇺🇸Detroit, Michigan, United States
Princess Alexandria Hospital
🇦🇺Woolloongabba, Australia
Hadassah Universtiy Hospital - Ein Kerem
🇮🇱Jerusalem, Israel
Hospital Clinico San Borja Arriaran
🇨🇱Santiago, Chile
Hôpital Edouard Herriot
🇫🇷Lyon cedex 3, France
Hotel Dieu
🇫🇷Nantes, France
Hôpital Saint-Louis
🇫🇷Paris Cedex 10, France
Universitaetsklinikum Aachen
🇩🇪Aachen, Germany
Hopital Hautepierre
🇫🇷Strasbourg Cedex, France
Charite-Campus Benjamin Franklin
🇩🇪Berlin, Germany
Universitaet Koeln
🇩🇪Köln, Germany
Klinikum Neuperlach
🇩🇪Muenchen, Germany
Medizinische Klinik und Polyklinik II
🇩🇪Würzburg, Germany
Shirdi Sai Baba Cancer Hospital K. M. C. Hospital
🇮🇳Manipal, Kama, India
Deenanath Mangeshkar Hospital & Research Centre
🇮🇳Pune, Mahara, India
Global Hospitals & Health City
🇮🇳Chennai, Tamilna, India
Sterling Hospital
🇮🇳Ahmedabad, India
Apollo Hospitals
🇮🇳Hyderabad, India
Sahyadri Specialty Hospital
🇮🇳Pune, India
Sourasky MC Ichilov Hospital Tel Aviv
🇮🇱Tel Aviv, Israel
Gachon University Gil Hospital
🇰🇷Incheon, Korea, Republic of
The Catholic University of Korea
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
American University of Beirut Medical Center
🇱🇧Beirut, Lebanon
Clinique Dr. Rizk
🇱🇧Beirut, Lebanon
Antiguo Hospital Civil de Guadalajara Fray Antonio Alcalde
🇲🇽Guadalajara, Mexico
Rafik Hariri University Hospital
🇱🇧Beirut, Lebanon
Instituto Nacional de Ciencias Medicas y Nutricion Salvador
🇲🇽Mexico City, Mexico
Hospital Central Dr Ignacio Morones Prieto
🇲🇽San Luis Potosi, Mexico
Samodzielny Publiczny Centralny Szpital Kliniczny
🇵🇱Warszawa, Poland
S.I. Russian Oncological Research Center n.a. N.N. Blokhin
🇷🇺Moscow, Russian Federation
State Institution "Hematology Research Center" RAMS
🇷🇺Moscow, Russian Federation
Republican Hospital named after V.A. Baranov
🇷🇺Petrozavodsk, Russian Federation
St-Petersburg MA Postgraduate Education
🇷🇺St. Petersburg, Russian Federation
Private Practice
🇿🇦Lyttleton, Gauteng, South Africa
Songklanagarind Hospital
🇹🇭Hat Yai, Thailand
Maharat Nakhon Ratchasima Hospital
🇹🇭Muang, Thailand
Srinagarind Hospital
🇹🇭Muang, Thailand