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

NCT ID: NCT01598831

Last Updated: 2020-04-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 816 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-29
• Study Completion Date: 2019-02-28

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.

Conditions

Severe Sepsis; Coagulopathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

ART-123

Group Type: ACTIVE_COMPARATOR

ART-123

Intervention Type: DRUG

Dose: 0.06 mg/kg/day up to a maximum dose of 6 mg/day for 6 days

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Dose: 0.06 mg/kg/day up to a maximum dose of 6 mg/day for 6 days.

Interventions

ART-123

Dose: 0.06 mg/kg/day up to a maximum dose of 6 mg/day for 6 days

Intervention Type: DRUG

Placebo

Dose: 0.06 mg/kg/day up to a maximum dose of 6 mg/day for 6 days.

Intervention Type: DRUG

Other Intervention Names

human recombinant thrombomodulin; thrombomodulin alfa

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Asahi Kasei Pharma America Corporation

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Fineberg, M.D.

Role: STUDY_DIRECTOR

Asahi Kasei Pharma America Corporation

Locations

Mobile, Alabama, United States

Phoenix, Arizona, United States

Atlanta, Georgia, United States

Idaho Falls, Idaho, United States

Indianapolis, Indiana, United States

Hazard, Kentucky, United States

Louisville, Kentucky, United States

Detroit Receiving Hospital

Detroit, Michigan, United States

Harper Hospital - Wayne State University School of Medicine

Detroit, Michigan, United States

Sinai-Grace Hospital

Detroit, Michigan, United States

Jackson, Mississippi, United States

Washington University in St. Louis

St Louis, Missouri, United States

Butte, Montana, United States

Englewood, New Jersey, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Durham, North Carolina, United States

Columbus, Ohio, United States

Oklahoma City, Oklahoma, United States

Philadelphia, Pennsylvania, United States

Rapid City, South Dakota, United States

2 of 2

Houston, Texas, United States

Murray, Utah, United States

Hospital Italiano de Cordoba

Córdoba, , Argentina

Prince of Wales Hospital

Randwick, New South Wales, Australia

Royal Brisbane and Women's Hospital

Herston, Queensland, Australia

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Bendigo Hospital

Bendigo, Victoria, Australia

Monash Medical Centre

Clayton, Victoria, Australia

Dandenong Hospital Monash Health

Dandenong, Victoria, Australia

Western Hospital

Footscray, Victoria, Australia

Austin Health

Heidelberg, Victoria, Australia

Sunshine Hospital

Melbourne, Victoria, Australia

UZ Antwerpen

Antwerp, , 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

Ghent, , Belgium

Clinique Saint-Pierre

Ottignies, , Belgium

UCL Mont-Godinne

Yvoir, , Belgium

Santa Casa de Misericordia de Belo Horizonte

Belo Horizonte, Minas Gerais, Brazil

Fundaçao Faculdade Regional de Medicina Sao Jose do Rio Preto

São José do Rio Preto, São Paulo, Brazil

Hospital Pompéia

Brasil, , Brazil

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

2 of 2

Calgary, Alberta, Canada

Calgary, Alberta, Canada

Calgary, Alberta, Canada

Vancouver, British Columbia, Canada

2 of 2

Vancouver, British Columbia, Canada

1 of 2

Victoria, British Columbia, Canada

Victoria, British Columbia, Canada

Winnipeg, Manitoba, Canada

Halifax, Nova Scotia, Canada

London, Ontario, Canada

1 of 2

Ottawa, Ontario, Canada

2 of 2

Ottawa, Ontario, Canada

Windsor, Ontario, Canada

Montreal, Quebec, Canada

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

University Hospital Brno, Department of Infectious Diseases

Brno, , Czechia

University Hospital Hradec Kralove, Department of Anaesthesiology, Resuscitation and Intensive Care

Hradec Králové, , Czechia

General University Hospital in Prague, Department of Anaesthesiology, Resuscitation and Intensive Medicine

Prague, , Czechia

University Hospital Kralovske Vinohrady, Department of Anesthesiology and Resuscitation

Prague, , Czechia

Masaryk´s Hospital Ustni nad Labem, o.z., Department of Infectious Diseases

Ústí nad Labem, , Czechia

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

Archet 1 University Hospital of Nice

Nice, Cedex 3, France

Service de reanimation médicale. CHU Hotel Dieu

Nantes, Nantes Cedex 01, France

CHU D'Anger

Angers, , France

CHU de Dijon, Hopital Bocage Central

Dijon, , France

CH-Hôpital Albert Michallon

Grenoble, , France

Centre Hospitalier Départemental de Vendée-Les Oudairies

La Roche-sur-Yon, , France

CHRU Lille-Pole Reanimation

Lille, , France

CHU Limoges

Limoges, , France

Centre Hospitalier Universitaire Nîmes

Nîmes, , France

La Pitié Salpétrière, Paris

Paris, , France

Hôpital COCHIN

Paris, , France

University Hospital of Bordeaux

Pessac, , France

CH Lyon Sud

Pierre-Bénite, , France

Nouvel hospital civil

Strasbourg, , France

Hôpital Sainte Musse

Toulon, , France

CHU Tours, Hopital Bretonneau

Tours, , France

Universitätsklinikum der RWTH Aachen

Aachen, , Germany

Helios Klinikum Erfurt

Erfurt, , Germany

Klinikum der Johann-Wolfgang Goethe-Universität

Frankfurt am Main, , Germany

Szent Imre Hospital, Anesthesiology and Intensive Care Unit

Budapest, , Hungary

Shalby Hospital

Ahmedabad, Gujarat, India

Shalby

Ahmedabad, Gujarat, India

Artemis Hospital

Gurgaon, Haryana, India

Ruby Hall Clinic

Pune, Maharashtra, India

Noble Hospital

Pune, Maharashtra, India

King Edward Memorial Hospital & Research Centre

Pune, Maharashtra, India

Maulana Azad Medical College and Associated L N Hospital

New Delhi, National Capital Territory of Delhi, 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

Mazumdar Shaw Medical Centre (Unit of Narayana Health)

Bangalore, , India

KLES Dr. Prabhakar Kore Hospital & Medical Research Centre

Belagavi, , India

JSS Hospital

Mysore, , India

Care Hospital

Nagpur, , India

Noble Hospital

Pune, , India

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

Petah Tikva, , Israel

Kaplan Medical Center

Rehovot, , Israel

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

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

Hawkes Bay Regional Hospital Intensive Care Unit Omahu Road

Hastings, , New Zealand

Wellington District Health Board

Newtown, , New Zealand

Hospital Nacional Almenara Yrigoyen - EsSALUD

Lima, Lima Province, Peru

Hospital Nacional FAP

Lima, Lima Province, Peru

Arkhangelsk Regional Clinical Hospital

Arkhangelsk, , Russia

Volosevich City Clinical Hospital #1

Arkhangelsk, , Russia

City Clinical Hospital #3 n.a. M.A. Pogorbunskiy

Kemerovo, , Russia

Kuban State Medical University (Site Facility: Krasnodar Regional Clinical Hospital #2)

Krasnodar, , Russia

Krasnoyarsk Regional Clinocal Hospital

Krasnoyarsk, , Russia

Vishnevsky Institute of Surgery

Moscow, , Russia

St George City Hospital

Saint Petersburg, , Russia

Aleksandrovskaya City Hospital

Saint Petersburg, , Russia

City Hospital #40

Saint Petersburg, , Russia

Mariinskaya City Hospital

Saint Petersburg, , Russia

Mechnikov North-Western State Medical University n.a. I.I. Mechnikov

Saint Petersburg, , Russia

City Hospital #4

Sochi, , Russia

Clinic for Infectious Diseases, Clinical Center Nis

Niš, , Serbia

Korea University Anam Hospital

Seongdu, , South Korea

Asan Medical Center

Seoul, , South Korea

Samsung Medical Center [Pulmonology]

Seoul, , South Korea

Seoul National University Hospital

Seoul, , South Korea

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

Chi Mei Medical Center Yong Kang

Yongkang District, Tainan, Taiwan

Taichung Veterans General Hospital [Pulmonology]

Taichung, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Birmingham Heartlands Hospital

Birmingham, , United Kingdom

Hull Royal Infirmary

Hull, , United Kingdom

Royal Liverpool University Hospital

Liverpool, , United Kingdom

Manchester Royal Infirmary

Manchester, , United Kingdom

Derriford Hospital

Plymouth, , United Kingdom

Countries

United States; Argentina; Australia; Belgium; Brazil; Bulgaria; Canada; Croatia; Czechia; Finland; France; Germany; Hungary; India; Israel; Netherlands; New Zealand; Peru; Russia; Serbia; South Korea; Spain; Taiwan; United Kingdom

References

Levi M, Vincent JL, Tanaka K, Radford AH, Kayanoki T, Fineberg DA, Hoppensteadt D, Fareed J. Effect of a Recombinant Human Soluble Thrombomodulin on Baseline Coagulation Biomarker Levels and Mortality Outcome in Patients With Sepsis-Associated Coagulopathy. Crit Care Med. 2020 Aug;48(8):1140-1147. doi: 10.1097/CCM.0000000000004426.

Reference Type: DERIVED

PMID: 32697484 (View on PubMed)

Vincent JL, Francois B, Zabolotskikh I, Daga MK, Lascarrou JB, Kirov MY, Pettila V, Wittebole X, Meziani F, Mercier E, Lobo SM, Barie PS, Crowther M, Esmon CT, Fareed J, Gando S, Gorelick KJ, Levi M, Mira JP, Opal SM, Parrillo J, Russell JA, Saito H, Tsuruta K, Sakai T, Fineberg D; SCARLET Trial Group. Effect of a Recombinant Human Soluble Thrombomodulin on Mortality in Patients With Sepsis-Associated Coagulopathy: The SCARLET Randomized Clinical Trial. JAMA. 2019 May 28;321(20):1993-2002. doi: 10.1001/jama.2019.5358.

Reference Type: DERIVED

PMID: 31104069 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://internationalsepsisforum.com/

Information on sepsis and treatment

Other Identifiers

3-001

Identifier Type: -

Identifier Source: org_study_id