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Phase 3 Safety and Efficacy Study of ART-123 in Subjects With Severe Sepsis and Coagulopathy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01598831
Recruitment Status : Active, not recruiting
First Posted : May 15, 2012
Last Update Posted : March 23, 2018
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Severe Sepsis Coagulopathy Drug: ART-123 Drug: Placebo Phase 3

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 814 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Assess the Safety and Efficacy of ART-123 in Subjects With Severe Sepsis and Coagulopathy.
Study Start Date : August 2012
Estimated Primary Completion Date : August 2018
Estimated Study Completion Date : July 2019

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: ART-123 Drug: ART-123
Dose: 0.06 mg/kg/day up to a maximum dose of 6 mg/day for 6 days
Other Name: human recombinant thrombomodulin
Placebo Comparator: Placebo Drug: Placebo
Dose: 0.06 mg/kg/day up to a maximum dose of 6 mg/day for 6 days.



Primary Outcome Measures :
  1. Primary Efficacy Outcome Measure [ Time Frame: 28 days ]
    28 day all-cause mortality

  2. Primary Safety Outcome Measure [ Time Frame: Through Study Day 28 ]
    Adverse Events

  3. Primary Safety Outcome Measure [ Time Frame: Through Study Day 28 ]

    Major Bleeding Events defined below will be closely monitored and systematically collected as Serious Adverse Events:

    • 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.6 (Investigator assessment for seriousness criteria.)

  4. Primary Safety Outcome Measure [ Time Frame: Through Study Day 28 ]
    Serious Adverse Events


Secondary Outcome Measures :
  1. Secondary Efficacy Outcome Measure [ Time Frame: 3 months ]
    Follow up all-cause mortality at 3 months

  2. Secondary Efficacy Outcome Measure [ Time Frame: 28 days ]
    Resolution of organ dysfunction as measured through day 28 by shock free, ventilator free, dialysis free plus alive days.

  3. Secondary Safety Outcome Measure [ Time Frame: 18 months ]
    Presence of Anti-drug antibodies up to 18 months



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01598831


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Locations
United States, Alabama
Mobile, Alabama, United States, 36608
United States, Arizona
Phoenix, Arizona, United States, 85008
Tucson, Arizona, United States, 85724
United States, California
Stanford University
Stanford, California, United States, 94305
United States, Florida
Miami, Florida, United States, 33125
Tampa General Hospital
Tampa, Florida, United States, 33606
United States, Georgia
Atlanta, Georgia, United States, 30342
United States, Idaho
Idaho Falls, Idaho, United States, 83404
United States, Indiana
Indianapolis, Indiana, United States, 46202
United States, Kansas
Kansas City, Kansas, United States, 66160-7381
United States, Kentucky
Hazard, Kentucky, United States, 41701
Louisville, Kentucky, United States, 40202
United States, Massachusetts
Boston, Massachusetts, United States, 02115
United States, Michigan
Detroit Receiving Hospital
Detroit, Michigan, United States, 48201
Harper Hospital - Wayne State University School of Medicine
Detroit, Michigan, United States, 48201
Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
Sinai-Grace Hospital
Detroit, Michigan, United States, 48235
United States, Mississippi
Jackson, Mississippi, United States, 39216
United States, Missouri
Washington University in St. Louis
Saint Louis, Missouri, United States, 63110
Saint Louis, Missouri, United States, 63110
United States, Montana
Butte, Montana, United States, 59701
United States, New Jersey
Englewood, New Jersey, United States, 07631
United States, New York
Buffalo, New York, United States, 14215
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, North Carolina
Durham, North Carolina, United States, 27710
United States, Ohio
Columbus, Ohio, United States, 43215
United States, Oklahoma
Oklahoma City, Oklahoma, United States, 73104
United States, Oregon
Portland, Oregon, United States, 97239
United States, Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, South Dakota
Rapid City, South Dakota, United States, 57701
United States, Tennessee
Nashville, Tennessee, United States, 37232-2560
United States, Texas
Baylor University Medical Center
Dallas, Texas, United States, 75246
2 of 2
Houston, Texas, United States, 77030
United States, Utah
Murray, Utah, United States, 84107
United States, Virginia
Falls Church, Virginia, United States, 22042
United States, Wisconsin
Milwaukee, Wisconsin, United States, 53226
Argentina
Hospital Italiano de Cordoba
Cordoba, Argentina, X5004BAL
Australia, New South Wales
Prince of Wales Hospital
Randwick, New South Wales, Australia
Australia, Queensland
Royal Brisbane and Women's Hospital
Herston, Queensland, Australia
Princess Alexandra Hospital
Woolloongabba, Queensland, Australia
Australia, South Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia, 5000
Australia, Victoria
Bendigo Hospital
Bendigo, Victoria, Australia
Monash Medical Centre
Clayton, Victoria, Australia
Dandenong Hospital Monash Health
Dandenong, Victoria, Australia, 3175
Western Hospital
Footscray, Victoria, Australia
Austin Health
Heidelberg, Victoria, Australia
Sunshine Hospital
Melbourne, Victoria, Australia, 3021
Belgium
UZ Antwerpen
Antwerpen, Belgium
Cliniques Du Sud-Luxerbourg (CSL), Hospital Saint Joseph
Arlon, Belgium
CHU Brugmann
Brussels, Belgium
Hopital Erasme
Brussels, Belgium
Hopitaux Iris Sud
Brussels, Belgium
UCL St. Luc
Brussels, Belgium
UZ Brussel
Brussels, Belgium
Centre Hospitalier de Dinant
Dinant, Belgium
UZ Gent
Gent, Belgium
Clinique Saint-Pierre
Ottignies, Belgium
UCL Mont-Godinne
Yvoir, Belgium
Brazil
Santa Casa de Misericordia de Belo Horizonte
Belo Horizonte, MG, Brazil
Santa Casa de Misericordia de Porto Alegre
Porto Alegre, RS, Brazil, 90020-090
Hospital São Lucas da PUCRS
Porto Alegre, RS, Brazil, 90610
Fundaçao Faculdade Regional de Medicina Sao Jose do Rio Preto
Sao Jose do Rio Preto, SP, Brazil
Hospital Samaritano
São Paulo, SP, Brazil, 01232-010
Hospital Pompéia
Brasil, Brazil, 95010-005
Bulgaria
Anesthesiology and Intensive Care Clinic, University Multiprofile Hospital For Active Treatment "Sveti Georgi", Plovdiv
Plovdiv, Bulgaria
Department of Anesthesiology and Intensive Care Multiprofile Hospital For Active Treatment "Tokuda Hospital Sofia", Sofia
Sofia, Bulgaria
Canada, Alberta
2 of 2
Calgary, Alberta, Canada, T1Y 6J4
Calgary, Alberta, Canada, T2V 1PA
Calgary, Alberta, Canada, T3M 1M4
1 of 2
Calgary, Alberta, Canada, T5H3V9
Canada, British Columbia
Vancouver, British Columbia, Canada, V5Z 1M9
2 of 2
Vancouver, British Columbia, Canada, V6Z 1Y6
1 of 2
Victoria, British Columbia, Canada, V8R-1J8
Victoria, British Columbia, Canada, V8R1J8
Canada, Manitoba
Winnipeg, Manitoba, Canada
Canada, Nova Scotia
Halifax, Nova Scotia, Canada
Canada, Ontario
London, Ontario, Canada, N6A5W9
1 of 2
Ottawa, Ontario, Canada, KIH 8L6
2 of 2
Ottawa, Ontario, Canada, KIH 8L6
North York General Hospital
Toronto, Ontario, Canada, M2K 1E1
Mount Sinai Hospital
Toronto, Ontario, Canada, M5G 1X5
Windsor, Ontario, Canada
Canada, Quebec
Montreal, Quebec, Canada
Canada
Quebec, Canada, G1V 4G5
Croatia
Clinical Hospital Center Zagreb, Medical ICU
Zagreb, Croatia
Clinical Hospital Dubrava, Department of Anesthesiology and resuscitation
Zagreb, Croatia
University Hospital Center Zagreb, Department of Anesthesiology, Reanimatology and Intensive Care Medicine
Zagreb, Croatia
Czechia
University Hospital Brno, Department of Anaesthesiology, Resuscitation and Intensive Medicine
Brno, Czech Rep, Czechia, 62500
University Hospital Motol
Praha, Czech Rep, Czechia, 15006
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
Finland
Helsingin Yliopistollinen Keskussairaala (HYKS) (Helsinki University Central Hospital (HUCH))
Helsinki, Finland
Keski-Suomen Keskussairaala (Central Finland Central Hospital)
Jyväskylä, Finland
Kuopion Yliopistollinen Sairaala (KYS) (Kuopio University Hospital)
Kuopio, Finland
Tampereen Yliopistollinen Sairaala (Tampere University Hospital) (TAYS) - Keskussairaala (Central Hospital)
Tampere, Finland
Turku University Hospital
Turku, Finland, 20520
France
Archet 1 University Hospital of Nice
Nice, Cedex 3, France, 23079
Service de reanimation médicale. CHU Hotel Dieu
Nantes, Nantes Cedex 01, France, 44093
CHU D'Anger
Angers Cedex 9, France
CHU de Dijon, Hopital Bocage Central
Dijon, France, 21000
CH-Hôpital Albert Michallon
Grenoble cedex 09, France
Centre Hospitalier Départemental de Vendée-Les Oudairies
La Roche-Sur-Yon cedex 9, France
CHRU Lille-Pole Reanimation
Lille, France, 59037
CHU Limoges
Limoges cedex, France
Hospices Civils de Lyon - Hopital de la Croix-Rousse
Lyon, France, 69004
Centre Hospitalier Universitaire Nîmes
Nîmes Cedex 9, France
La Pitié Salpétrière, Paris
Paris, France, 75013
Hôpital COCHIN
Paris, France
Reanimation Hôpital Saint Antoine
Paris, France
University Hospital of Bordeaux
Pessac, France, 33600
CH Lyon Sud
Pierre-Bénite cedex, France
Nouvel hospital civil
Strasbourg, France, 67000
Hôpital Sainte Musse
Toulon, France
CHU Tours, Hopital Bretonneau
Tours, France
Hôpital de Brabois Rue de Morvan
Vandoeuvre-les-Nancy, France
Germany
Universitätsklinikum der RWTH Aachen
Aachen, Germany, 54074
Vivantes Klinikum Neukölln
Berlin, Germany, 12351
Helios Klinikum Erfurt
Erfurt, Germany
Klinikum der Johann-Wolfgang Goethe-Universität
Frankfurt am Main, Germany
Universitätsklinikum Leipzig AöR
Leipzig, Germany
Hungary
Szent Imre Hospital, Anesthesiology and Intensive Care Unit
Budapest, Hungary, 1115
India
Maulana Azad Medical College and Associated L N Hospital
New Delhi, Delhi, India
Shalby Hospital
Ahmedabad,, Gujarat, India, 380015
Shalby
Ahmedabad, Gujarat, India
Artemis Hospital
Gurgaon, Haryana, India, 122001
Ruby Hall Clinic
Pune, Maharashtra, India, 411011
Noble Hospital
Pune, Maharashtra, India, 411013
King Edward Memorial Hospital & Research Centre
Pune, Maharashtra, India
Hi-tech Medical College & Hospital
Bhubaneswar, Odisha, India
Bharati Vidyapeeth Deemed University Medical College Bharti Hospital and Research Centre
Pune, Pune, Maharashtra, India, 411043
St. Theresa Hospital
Hyderabad, Telangana State, India, 500018
Mazumdar Shaw Medical Centre (Unit of Narayana Health)
Bangalore, India, 560099
KLES Dr. Prabhakar Kore Hospital & Medical Research Centre
Belgaum, India, 590010
JSS Hospital
Mysore, India, 570004
Care Hospital
Nagpur, India, 440010
Noble Hospital
Pune, India, 411013
Israel
Barzilai Medical Center
Ashkelon, Israel
Rambam Medical Center
Haifa, Israel
The Lady Davis Carmel Medical Center
Haifa, Israel
Shaare Zedek Medical Center
Jerusalem, Israel
Rabin Medical Center
Petach Tikva, Israel
Kaplan Medical Center
Rehovot, Israel
Korea, Republic of
Busan Paik Hospital
Busan, Korea, Republic of
Gachon University Gil Medical Center [Infectious Disease]
Incheon, Korea, Republic of
Korea University Anam Hospital
Seongdu, Korea, Republic of
Asan Medical Center
Seoul, Korea, Republic of
Samsung Medical Center [Pulmonology]
Seoul, Korea, Republic of
Seoul National University Hospital
Seoul, Korea, Republic of
Yonsei University Medical Center
Soeul, Korea, Republic of
Netherlands
Jeroen Bosch Ziekenhuis
's-Hertogenbosch, Netherlands
VUMC
Amsterdam, Netherlands
Ziekenhuis Gelderse Vallei
Ede, Netherlands
Medisch Spectrum Twente
Enschede, Netherlands
University Medical Center Groningen
Groningen, Netherlands
Atrium MC Heerlen
Heerlen, Netherlands
Medisch Centrum Leeuwarden
Leeuwarden, Netherlands
Canisius-Wilhelmina Ziekenhuis
Nijmegen, Netherlands, 6532 SZ
UMC St. Radboud
Nijmegen, Netherlands
Ikazia Ziekenhuis
Rotterdam, Netherlands
New Zealand
Auckland District Health Board
Auckland, New Zealand
Christchurch Hospital
Christchurch, New Zealand
Hawkes Bay Regional Hospital Intensive Care Unit Omahu Road
Hastings, New Zealand
Wellington District Health Board
Newtown, New Zealand, 6021
Peru
Hospital Nacional Almenara Yrigoyen - EsSALUD
Lima, Lima Province, Peru
Hospital Nacional FAP
Lima, Lima Province, Peru
Russian Federation
Arkhangelsk Regional Clinical Hospital
Arkhangelsk, Russian Federation
Volosevich City Clinical Hospital #1
Arkhangelsk, Russian Federation
City Clinical Hospital #3 n.a. M.A. Pogorbunskiy
Kemerovo, Russian Federation, 650000
Kuban State Medical University (Site Facility: Krasnodar Regional Clinical Hospital #2)
Krasnodar, Russian Federation
Krasnoyarsk Regional Clinocal Hospital
Krasnoyarsk, Russian Federation, 660022
I.M. Sechenov Moscow State Budgetary Medical University
Moscow, Russian Federation
Vishnevsky Institute of Surgery
Moscow, Russian Federation
City Clinical Hospital #1
Novosibirsk, Russian Federation
St George City Hospital
Saint Petersburg, Russian Federation, 194354
City Hospital #40
Saint Petersburg, Russian Federation
St. Petersburg Janelidze Emergency Research Institute
Saint Petersburg, Russian Federation
City Hospital #4
Sochi, Russian Federation, 354057
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
Serbia
Clinic for Infectious Diseases, Clinical Center Nis
Nis, Serbia
Spain
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 Clínico San Carlos
Madrid, Spain
Hospital de Sabadell
Sabadell, Spain
Hospital Universitari de Tarragona Joan XXIII
Tarragona, Spain
Taiwan
Chi Mei Medical Center Yong Kang
Yongkang, Tainan, Taiwan
Taichung Veterans General Hospital [Pulmonology]
Taichung, Taiwan
National Taiwan University Hospital
Taipei, Taiwan
United Kingdom
Heart of England NHS Trust (Good Hope Hospital)
Birmingham, United Kingdom, B75 7RR
Birmingham Heartlands Hospital
Birmingham, United Kingdom, B9 5SS
University Hospital of Wales
Cardiff, United Kingdom, CF14 4XW
Hull Royal Infirmary HICU 1
Hull, United Kingdom, HU3 2JZ
Hull Royal Infirmary
Hull, United Kingdom, HU3 2JZ
Royal Liverpool University Hospital
Liverpool, United Kingdom
Manchester Royal Infirmary
Manchester, United Kingdom
Norfolk and Norwich University Hospital NHS Foundation Trust
Norwich, United Kingdom, NR4 7UY
Derriford Hospital
Plymouth, United Kingdom
Sponsors and Collaborators
Asahi Kasei Pharma America Corporation
Investigators
Study Director: David Fineberg, M.D. Asahi Kasei Pharma America Corporation

Additional Information:
Responsible Party: Asahi Kasei Pharma America Corporation
ClinicalTrials.gov Identifier: NCT01598831     History of Changes
Other Study ID Numbers: 3-001
First Posted: May 15, 2012    Key Record Dates
Last Update Posted: March 23, 2018
Last Verified: March 2018

Keywords provided by Asahi Kasei Pharma America Corporation:
sepsis

Additional relevant MeSH terms:
Sepsis
Toxemia
Blood Coagulation Disorders
Hemostatic Disorders
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Hematologic Diseases
Vascular Diseases
Cardiovascular Diseases
Hemorrhagic Disorders