Phase 3 Safety and Efficacy Study of ART-123 in Subjects With Severe Sepsis and Coagulopathy
- Registration Number
- NCT01598831
- Lead Sponsor
- Asahi Kasei Pharma America Corporation
- Brief Summary
The purpose of the study is to evaluate if ART-123 given to patients who have severe sepsis can decrease mortality.
- Detailed Description
Study is to evaluate if ART-123 given to patients who have severe sepsis complicated by at least one organ dysfunction and coagulopathy can decrease mortality.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 816
- Subject must be receiving treatment in an ICU, or in an acute care setting (e.g., ER, RR)
- Clinical objective evidence of bacterial infection and a known site of infection.
- Cardiovascular dysfunction or Respiratory Failure due to sepsis.
- Coagulopathy characterized by an INR >1.40 without other known causes.
- Subject or Authorized Representative is unable to provide informed consent.
- Subject is pregnant or breastfeeding or intends to get pregnant within 28 days of enrolling into the study.
- Subject is of childbearing potential and does not have a negative pregnancy test.
- Subject is < 18 years of age.
- Subject has a known allergy to ART-123 or any components of the drug product.
- Subject is unwilling to allow transfusion of blood or blood products.
- Subject has an advance directive to withhold life-sustaining treatment.
- Subject has had previous treatment with ART-123.
- Body weight ≥ 175 kg.
- Platelets < 30,000/ mm3 for any reason, PT prolongation or thrombocytopenia that is not due to sepsis.
- Any surgery that is potentially hemorrhagic (e.g. intra-thoracic, intra-abdominal or non-traumatic orthopedic surgery of the femur or pelvis) that is completed within 12 hours prior to first dose of study drug, or ongoing impairment of hemostasis as a result of one of these procedures
- History of head trauma, spinal trauma, or other acute trauma with an increased risk of bleeding within 3 months prior to consent.
- Cerebral Vascular Accident (CVA) within 3 months prior to consent.
- Any history of intracerebral arteriovenous malformation (AVM), cerebral aneurysm, or mass lesions of the central nervous system.
- History of congenital bleeding diathesesor anatomical anomaly that predisposes to hemorrhage (e.g. hemophilia, hereditary hemorrhagic telangiectasia).
- Significant gastrointestinal bleeding within 6 weeks prior to consent.
- Subject is diagnosed with a known medical condition associated with a hypercoagulable state.
- Child-Pugh score of 10-15 (Class C)
- Portosystemic hypertension or known history of bleeding esophageal varices.
- History of solid organ, allogeneic bone marrow, or stem cell transplantation within the 6 months prior to consent.
- Acute pancreatitis where infection has not been documented by a positive blood or abdominal fluid culture or gram stain consistent with bacterial infection.
- Subjects with renal dysfunction defined as (a) Chronic renal failure requiring renal replacement therapy (RRT), or (b) Acute renal failure with onset of oliguria (urine output < 0.3 ml/kg/hr) > 48 hours prior to first dose of study drug whether receiving RRT or not
- Use of anticoagulants, antiplatelet agents, antithrombotics and thrombolytics within the 72 hours prior to first does of study drug.
- Life expectancy < 90 days.
- Current use of any chemotherapy agent likely to cause myeloablation (severe or complete depletion of bone marrow).
- Participation in another research study involving an investigational agent within 30 days prior to consent or projected study participation during the 28 days post study randomization.
- Confirmed or suspected endocarditis
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo - ART-123 ART-123 -
- Primary Outcome Measures
Name Time Method Number of Participants With 28-Day All-cause Mortality 28 days 28-Day All-cause Mortality
Number of Participants With On-Treatment Serious Major Bleeding Events Through Study Day 28 On-treatment Serious Major Bleeding Events collected as Serious Adverse Events and defined as: any intracranial hemorrhage, any life-threatening bleeding, any bleeding event classified as serious by the Investigator (e.g., resulting in permanent morbidity), or any bleeding that required the administration of 1440 ml (typically 6 units) of packed red cells over two consecutive days. (Investigator assessment for seriousness criteria.)
- Secondary Outcome Measures
Name Time Method Follow up All-cause Mortality at 3 Months 3 months Follow up all-cause mortality at 3 months
Number of Event Free and Alive Days to Measure Resolution of Organ Dysfunction 28 days Resolution of organ dysfunction as measured through day 28 by shock free, ventilator free, dialysis free plus alive days.
Number of Participants With Anti-drug Antibodies 18 months Presence of Anti-drug antibodies up to 18 months
Trial Locations
- Locations (131)
Washington University in St. Louis
🇺🇸Saint Louis, Missouri, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
2 of 2
🇨🇦Ottawa, Ontario, Canada
Prince of Wales Hospital
🇦🇺Randwick, New South Wales, Australia
Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia
Bendigo Hospital
🇦🇺Bendigo, Victoria, Australia
UZ Antwerpen
🇧🇪Antwerpen, Belgium
UCL St. Luc
🇧🇪Brussels, Belgium
Hopitaux Iris Sud
🇧🇪Brussels, Belgium
UZ Brussel
🇧🇪Brussels, Belgium
Centre Hospitalier de Dinant
🇧🇪Dinant, Belgium
Clinique Saint-Pierre
🇧🇪Ottignies, Belgium
UZ Gent
🇧🇪Gent, Belgium
UCL Mont-Godinne
🇧🇪Yvoir, Belgium
Santa Casa de Misericordia de Belo Horizonte
🇧🇷Belo Horizonte, MG, Brazil
Hospital Pompéia
🇧🇷Brasil, Brazil
Department of Anesthesiology and Intensive Care Multiprofile Hospital For Active Treatment "Tokuda Hospital Sofia", Sofia
🇧🇬Sofia, Bulgaria
Anesthesiology and Intensive Care Clinic, University Multiprofile Hospital For Active Treatment "Sveti Georgi", Plovdiv
🇧🇬Plovdiv, Bulgaria
Clinical Hospital Dubrava, Department of Anesthesiology and resuscitation
🇭🇷Zagreb, Croatia
University Hospital Center Zagreb, Department of Anesthesiology, Reanimatology and Intensive Care Medicine
🇭🇷Zagreb, Croatia
1 of 2
🇨🇦Ottawa, Ontario, Canada
Clinical Hospital Center Zagreb, Medical ICU
🇭🇷Zagreb, Croatia
University Hospital Brno, Department of Infectious Diseases
🇨🇿Brno, Czechia
University Hospital Hradec Kralove, Department of Anaesthesiology, Resuscitation and Intensive Care
🇨🇿Hradec Kralove, Czechia
University Hospital Kralovske Vinohrady, Department of Anesthesiology and Resuscitation
🇨🇿Prague 10, Czechia
General University Hospital in Prague, Department of Anaesthesiology, Resuscitation and Intensive Medicine
🇨🇿Prague 2, Czechia
Masaryk´s Hospital Ustni nad Labem, o.z., Department of Infectious Diseases
🇨🇿Usti nad Labem, Czechia
Keski-Suomen Keskussairaala (Central Finland Central Hospital)
🇫🇮Jyväskylä, Finland
Tampereen Yliopistollinen Sairaala (Tampere University Hospital) (TAYS) - Keskussairaala (Central Hospital)
🇫🇮Tampere, Finland
Kuopion Yliopistollinen Sairaala (KYS) (Kuopio University Hospital)
🇫🇮Kuopio, Finland
CHU D'Anger
🇫🇷Angers Cedex 9, France
Archet 1 University Hospital of Nice
🇫🇷Nice, Cedex 3, France
CHU de Dijon, Hopital Bocage Central
🇫🇷Dijon, France
Service de reanimation médicale. CHU Hotel Dieu
🇫🇷Nantes, Nantes Cedex 01, France
CHU Limoges
🇫🇷Limoges cedex, France
CHRU Lille-Pole Reanimation
🇫🇷Lille, France
Hôpital COCHIN
🇫🇷Paris, France
University Hospital of Bordeaux
🇫🇷Pessac, France
Centre Hospitalier Universitaire Nîmes
🇫🇷Nîmes Cedex 9, France
La Pitié Salpétrière, Paris
🇫🇷Paris, France
CH Lyon Sud
🇫🇷Pierre-Bénite cedex, France
CHU Tours, Hopital Bretonneau
🇫🇷Tours, France
Universitätsklinikum der RWTH Aachen
🇩🇪Aachen, Germany
Szent Imre Hospital, Anesthesiology and Intensive Care Unit
🇭🇺Budapest, Hungary
Helios Klinikum Erfurt
🇩🇪Erfurt, Germany
Klinikum der Johann-Wolfgang Goethe-Universität
🇩🇪Frankfurt am Main, Germany
Shalby
🇮🇳Ahmedabad, Gujarat, India
Shalby Hospital
🇮🇳Ahmedabad,, Gujarat, India
Noble Hospital
🇮🇳Pune, India
Artemis Hospital
🇮🇳Gurgaon, Haryana, India
Hi-tech Medical College & Hospital
🇮🇳Bhubaneswar, Odisha, India
Bharati Vidyapeeth Deemed University Medical College Bharti Hospital and Research Centre
🇮🇳Pune, Pune, Maharashtra, India
St. Theresa Hospital
🇮🇳Hyderabad, Telangana State, India
JSS Hospital
🇮🇳Mysore, India
Kaplan Medical Center
🇮🇱Rehovot, Israel
Care Hospital
🇮🇳Nagpur, India
The Lady Davis Carmel Medical Center
🇮🇱Haifa, Israel
Barzilai Medical Center
🇮🇱Ashkelon, Israel
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center [Pulmonology]
🇰🇷Seoul, Korea, Republic of
Korea University Anam Hospital
🇰🇷Seongdu, Korea, Republic of
Jeroen Bosch Ziekenhuis
🇳🇱's-Hertogenbosch, Netherlands
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Medisch Spectrum Twente
🇳🇱Enschede, Netherlands
Ziekenhuis Gelderse Vallei
🇳🇱Ede, Netherlands
VUMC
🇳🇱Amsterdam, Netherlands
Medisch Centrum Leeuwarden
🇳🇱Leeuwarden, Netherlands
UMC St. Radboud
🇳🇱Nijmegen, Netherlands
Ikazia Ziekenhuis
🇳🇱Rotterdam, Netherlands
Auckland District Health Board
🇳🇿Auckland, New Zealand
Christchurch Hospital
🇳🇿Christchurch, New Zealand
Arkhangelsk Regional Clinical Hospital
🇷🇺Arkhangelsk, Russian Federation
Wellington District Health Board
🇳🇿Newtown, New Zealand
Hawkes Bay Regional Hospital Intensive Care Unit Omahu Road
🇳🇿Hastings, New Zealand
Hospital Nacional Almenara Yrigoyen - EsSALUD
🇵🇪Lima, Lima Province, Peru
Hospital Nacional FAP
🇵🇪Lima, Lima Province, Peru
Volosevich City Clinical Hospital #1
🇷🇺Arkhangelsk, Russian Federation
City Clinical Hospital #3 n.a. M.A. Pogorbunskiy
🇷🇺Kemerovo, Russian Federation
St George City Hospital
🇷🇺Saint Petersburg, Russian Federation
Vishnevsky Institute of Surgery
🇷🇺Moscow, Russian Federation
City Hospital #40
🇷🇺Saint Petersburg, Russian Federation
City Hospital #4
🇷🇺Sochi, Russian Federation
Aleksandrovskaya City Hospital
🇷🇺St. Petersburg, Russian Federation
Mariinskaya City Hospital
🇷🇺St. Petersburg, Russian Federation
Mechnikov North-Western State Medical University n.a. I.I. Mechnikov
🇷🇺St. Petersburg, Russian Federation
Complexo Hospitalario Universitario A Coruña
🇪🇸A Coruña, Spain
Hospital Universitario Mutua Terrassa Intensive Care
🇪🇸Barcelona, Spain
Servicio de Medicina Intensiva Hospital Universitario Valle de Hebron
🇪🇸Barcelona, Spain
Hospital de Sabadell
🇪🇸Sabadell, Spain
Hospital Clínico San Carlos
🇪🇸Madrid, Spain
Hospital Universitari de Tarragona Joan XXIII
🇪🇸Tarragona, Spain
Taichung Veterans General Hospital [Pulmonology]
🇨🇳Taichung, Taiwan
Birmingham Heartlands Hospital
🇬🇧Birmingham, United Kingdom
Hull Royal Infirmary
🇬🇧Hull, United Kingdom
Manchester Royal Infirmary
🇬🇧Manchester, United Kingdom
Derriford Hospital
🇬🇧Plymouth, United Kingdom
Shaare Zedek Medical Center
🇮🇱Jerusalem, Israel
Maulana Azad Medical College and Associated L N Hospital
🇮🇳New Delhi, Delhi, India
Rambam Medical Center
🇮🇱Haifa, Israel
Cliniques Du Sud-Luxerbourg (CSL), Hospital Saint Joseph
🇧🇪Arlon, Belgium
Mazumdar Shaw Medical Centre (Unit of Narayana Health)
🇮🇳Bangalore, India
KLES Dr. Prabhakar Kore Hospital & Medical Research Centre
🇮🇳Belgaum, India
Rabin Medical Center
🇮🇱Petach Tikva, Israel
Kuban State Medical University (Site Facility: Krasnodar Regional Clinical Hospital #2)
🇷🇺Krasnodar, Russian Federation
Krasnoyarsk Regional Clinocal Hospital
🇷🇺Krasnoyarsk, Russian Federation
Clinic for Infectious Diseases, Clinical Center Nis
🇷🇸Nis, Serbia
Chi Mei Medical Center Yong Kang
🇨🇳Yongkang, Tainan, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Sinai-Grace Hospital
🇺🇸Detroit, Michigan, United States
Royal Brisbane and Women's Hospital
🇦🇺Herston, Queensland, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
King Edward Memorial Hospital & Research Centre
🇮🇳Pune, Maharashtra, India
CH-Hôpital Albert Michallon
🇫🇷Grenoble cedex 09, France
Centre Hospitalier Départemental de Vendée-Les Oudairies
🇫🇷La Roche-Sur-Yon cedex 9, France
Nouvel hospital civil
🇫🇷Strasbourg, France
Hôpital Sainte Musse
🇫🇷Toulon, France
Fundaçao Faculdade Regional de Medicina Sao Jose do Rio Preto
🇧🇷Sao Jose do Rio Preto, SP, Brazil
Detroit Receiving Hospital
🇺🇸Detroit, Michigan, United States
CHU Brugmann
🇧🇪Brussels, Belgium
Dandenong Hospital Monash Health
🇦🇺Dandenong, Victoria, Australia
Western Hospital
🇦🇺Footscray, Victoria, Australia
Austin Health
🇦🇺Heidelberg, Victoria, Australia
Hospital Italiano de Cordoba
🇦🇷Cordoba, Argentina
Helsingin Yliopistollinen Keskussairaala (HYKS) (Helsinki University Central Hospital (HUCH))
🇫🇮Helsinki, Finland
University Medical Center Groningen
🇳🇱Groningen, Netherlands
Harper Hospital - Wayne State University School of Medicine
🇺🇸Detroit, Michigan, United States
Sunshine Hospital
🇦🇺Melbourne, Victoria, Australia
Hopital Erasme
🇧🇪Brussels, Belgium
Monash Medical Centre
🇦🇺Clayton, Victoria, Australia
Ruby Hall Clinic
🇮🇳Pune, Maharashtra, India
Royal Liverpool University Hospital
🇬🇧Liverpool, United Kingdom