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

NCT01598831 | Completed Phase 3 Results DMC

• 1 other identifier: 3-001
• Study Type: interventional
• Target: 816
• Locations: 24 countries
• Sites: 161

Brief Summary

The purpose of the study is to evaluate if ART-123 given to patients who have severe sepsis can decrease mortality.

Conditions

Severe Sepsis; Coagulopathy

Keywords

sepsis

Outcome Measures

Primary Outcomes (2)

• Number of Participants With 28-Day All-cause Mortality

  28-Day All-cause Mortality

  28 days

• Number of Participants With On-Treatment Serious Major Bleeding Events

  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.)

  Through Study Day 28

Secondary Outcomes (3)

• Follow up All-cause Mortality at 3 Months

  3 months

• Number of Event Free and Alive Days to Measure Resolution of Organ Dysfunction

  28 days

• Number of Participants With Anti-drug Antibodies

  18 months

Study Arms (2)

ART-123

ACTIVE COMPARATOR

Drug: ART-123

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

ART-123 DRUG

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

Also known as: human recombinant thrombomodulin, thrombomodulin alfa

ART-123

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Asahi Kasei Pharma America Corporation: lead

Study Sites (161)

Unknown Facility

Mobile, Alabama, 36608, United States

Location

Unknown Facility

Phoenix, Arizona, 85008, United States

Location

Unknown Facility

Atlanta, Georgia, 30342, United States

Location

Unknown Facility

Idaho Falls, Idaho, 83404, United States

Location

Unknown Facility

Indianapolis, Indiana, 46202, United States

Location

Unknown Facility

Hazard, Kentucky, 41701, United States

Location

Unknown Facility

Louisville, Kentucky, 40202, United States

Location

Detroit Receiving Hospital

Detroit, Michigan, 48201, United States

Location

Harper Hospital - Wayne State University School of Medicine

Detroit, Michigan, 48201, United States

Location

Sinai-Grace Hospital

Detroit, Michigan, 48235, United States

Location

Unknown Facility

Jackson, Mississippi, 39216, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63110, United States

Location

Unknown Facility

Butte, Montana, 59701, United States

Location

Unknown Facility

Englewood, New Jersey, 07631, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Unknown Facility

Durham, North Carolina, 27710, United States

Location

Unknown Facility

Columbus, Ohio, 43215, United States

Location

Unknown Facility

Oklahoma City, Oklahoma, 73104, United States

Location

Unknown Facility

Philadelphia, Pennsylvania, 19104, United States

Location

Unknown Facility

Rapid City, South Dakota, 57701, United States

Location

2 of 2

Houston, Texas, 77030, United States

Location

Unknown Facility

Murray, Utah, 84107, United States

Location

Hospital Italiano de Cordoba

Córdoba, X5004BAL, Argentina

Location

Prince of Wales Hospital

Randwick, New South Wales, Australia

Location

Royal Brisbane and Women's Hospital

Herston, Queensland, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Bendigo Hospital

Bendigo, Victoria, Australia

Location

Monash Medical Centre

Clayton, Victoria, Australia

Location

Dandenong Hospital Monash Health

Dandenong, Victoria, 3175, Australia

Location

Western Hospital

Footscray, Victoria, Australia

Location

Austin Health

Heidelberg, Victoria, Australia

Location

Sunshine Hospital

Melbourne, Victoria, 3021, Australia

Location

UZ Antwerpen

Antwerp, Belgium

Location

Cliniques Du Sud-Luxerbourg (CSL), Hospital Saint Joseph

Arlon, Belgium

Location

CHU Brugmann

Brussels, Belgium

Location

Hopital Erasme

Brussels, Belgium

Location

Hopitaux Iris Sud

Brussels, Belgium

Location

UCL St. Luc

Brussels, Belgium

Location

UZ Brussel

Brussels, Belgium

Location

Centre Hospitalier de Dinant

Dinant, Belgium

Location

UZ Gent

Ghent, Belgium

Location

Clinique Saint-Pierre

Ottignies, Belgium

Location

UCL Mont-Godinne

Yvoir, Belgium

Location

Santa Casa de Misericordia de Belo Horizonte

Belo Horizonte, Minas Gerais, Brazil

Location

Fundaçao Faculdade Regional de Medicina Sao Jose do Rio Preto

São José do Rio Preto, São Paulo, Brazil

Location

Hospital Pompéia

Brasil, 95010-005, Brazil

Location

Anesthesiology and Intensive Care Clinic, University Multiprofile Hospital For Active Treatment "Sveti Georgi", Plovdiv

Plovdiv, Bulgaria

Location

Department of Anesthesiology and Intensive Care Multiprofile Hospital For Active Treatment "Tokuda Hospital Sofia", Sofia

Sofia, Bulgaria

Location

2 of 2

Calgary, Alberta, T1Y 6J4, Canada

Location

Unknown Facility

Calgary, Alberta, T2V 1PA, Canada

Location

Unknown Facility

Calgary, Alberta, T3M 1M4, Canada

Location

Unknown Facility

Vancouver, British Columbia, V5Z 1M9, Canada

Location

2 of 2

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

1 of 2

Victoria, British Columbia, V8R-1J8, Canada

Location

Unknown Facility

Victoria, British Columbia, V8R1J8, Canada

Location

Unknown Facility

Winnipeg, Manitoba, Canada

Location

Unknown Facility

Halifax, Nova Scotia, Canada

Location

Unknown Facility

London, Ontario, N6A5W9, Canada

Location

1 of 2

Ottawa, Ontario, KIH 8L6, Canada

Location

2 of 2

Ottawa, Ontario, KIH 8L6, Canada

Location

Unknown Facility

Windsor, Ontario, Canada

Location

Unknown Facility

Montreal, Quebec, Canada

Location

Clinical Hospital Center Zagreb, Medical ICU

Zagreb, Croatia

Location

Clinical Hospital Dubrava, Department of Anesthesiology and resuscitation

Zagreb, Croatia

Location

University Hospital Center Zagreb, Department of Anesthesiology, Reanimatology and Intensive Care Medicine

Zagreb, Croatia

Location

University Hospital Brno, Department of Infectious Diseases

Brno, Czechia

Location

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

Hradec Králové, Czechia

Location

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

Prague, Czechia

Location

University Hospital Kralovske Vinohrady, Department of Anesthesiology and Resuscitation

Prague, Czechia

Location

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

Ústí nad Labem, Czechia

Location

Helsingin Yliopistollinen Keskussairaala (HYKS) (Helsinki University Central Hospital (HUCH))

Helsinki, Finland

Location

Keski-Suomen Keskussairaala (Central Finland Central Hospital)

Jyväskylä, Finland

Location

Kuopion Yliopistollinen Sairaala (KYS) (Kuopio University Hospital)

Kuopio, Finland

Location

Tampereen Yliopistollinen Sairaala (Tampere University Hospital) (TAYS) - Keskussairaala (Central Hospital)

Tampere, Finland

Location

Archet 1 University Hospital of Nice

Nice, Cedex 3, 23079, France

Location

Service de reanimation médicale. CHU Hotel Dieu

Nantes, Nantes Cedex 01, 44093, France

Location

CHU D'Anger

Angers, France

Location

CHU de Dijon, Hopital Bocage Central

Dijon, 21000, France

Location

CH-Hôpital Albert Michallon

Grenoble, France

Location

Centre Hospitalier Départemental de Vendée-Les Oudairies

La Roche-sur-Yon, France

Location

CHRU Lille-Pole Reanimation

Lille, 59037, France

Location

CHU Limoges

Limoges, France

Location

Centre Hospitalier Universitaire Nîmes

Nîmes, France

Location

La Pitié Salpétrière, Paris

Paris, 75013, France

Location

Hôpital COCHIN

Paris, France

Location

University Hospital of Bordeaux

Pessac, 33600, France

Location

CH Lyon Sud

Pierre-Bénite, France

Location

Nouvel hospital civil

Strasbourg, 67000, France

Location

Hôpital Sainte Musse

Toulon, France

Location

CHU Tours, Hopital Bretonneau

Tours, France

Location

Universitätsklinikum der RWTH Aachen

Aachen, 54074, Germany

Location

Helios Klinikum Erfurt

Erfurt, Germany

Location

Klinikum der Johann-Wolfgang Goethe-Universität

Frankfurt am Main, Germany

Location

Szent Imre Hospital, Anesthesiology and Intensive Care Unit

Budapest, 1115, Hungary

Location

Shalby Hospital

Ahmedabad, Gujarat, 380015, India

Location

Shalby

Ahmedabad, Gujarat, India

Location

Artemis Hospital

Gurgaon, Haryana, 122001, India

Location

Ruby Hall Clinic

Pune, Maharashtra, 411011, India

Location

Noble Hospital

Pune, Maharashtra, 411013, India

Location

King Edward Memorial Hospital & Research Centre

Pune, Maharashtra, India

Location

Maulana Azad Medical College and Associated L N Hospital

New Delhi, National Capital Territory of Delhi, India

Location

Hi-tech Medical College & Hospital

Bhubaneswar, Odisha, India

Location

Bharati Vidyapeeth Deemed University Medical College Bharti Hospital and Research Centre

Pune, Pune, Maharashtra, 411043, India

Location

St. Theresa Hospital

Hyderabad, Telangana State, 500018, India

Location

Mazumdar Shaw Medical Centre (Unit of Narayana Health)

Bangalore, 560099, India

Location

KLES Dr. Prabhakar Kore Hospital & Medical Research Centre

Belagavi, 590010, India

Location

JSS Hospital

Mysore, 570004, India

Location

Care Hospital

Nagpur, 440010, India

Location

Noble Hospital

Pune, 411013, India

Location

Barzilai Medical Center

Ashkelon, Israel

Location

Rambam Medical Center

Haifa, Israel

Location

The Lady Davis Carmel Medical Center

Haifa, Israel

Location

Shaare Zedek Medical Center

Jerusalem, Israel

Location

Rabin Medical Center

Petah Tikva, Israel

Location

Kaplan Medical Center

Rehovot, Israel

Location

Jeroen Bosch Ziekenhuis

's-Hertogenbosch, Netherlands

Location

VUMC

Amsterdam, Netherlands

Location

Ziekenhuis Gelderse Vallei

Ede, Netherlands

Location

Medisch Spectrum Twente

Enschede, Netherlands

Location

University Medical Center Groningen

Groningen, Netherlands

Location

Medisch Centrum Leeuwarden

Leeuwarden, Netherlands

Location

UMC St. Radboud

Nijmegen, Netherlands

Location

Ikazia Ziekenhuis

Rotterdam, Netherlands

Location

Auckland District Health Board

Auckland, New Zealand

Location

Christchurch Hospital

Christchurch, New Zealand

Location

Hawkes Bay Regional Hospital Intensive Care Unit Omahu Road

Hastings, New Zealand

Location

Wellington District Health Board

Newtown, 6021, New Zealand

Location

Hospital Nacional Almenara Yrigoyen - EsSALUD

Lima, Lima Province, Peru

Location

Hospital Nacional FAP

Lima, Lima Province, Peru

Location

Arkhangelsk Regional Clinical Hospital

Arkhangelsk, Russia

Location

Volosevich City Clinical Hospital #1

Arkhangelsk, Russia

Location

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

Kemerovo, 650000, Russia

Location

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

Krasnodar, Russia

Location

Krasnoyarsk Regional Clinocal Hospital

Krasnoyarsk, 660022, Russia

Location

Vishnevsky Institute of Surgery

Moscow, Russia

Location

St George City Hospital

Saint Petersburg, 194354, Russia

Location

Aleksandrovskaya City Hospital

Saint Petersburg, Russia

Location

City Hospital #40

Saint Petersburg, Russia

Location

Mariinskaya City Hospital

Saint Petersburg, Russia

Location

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

Saint Petersburg, Russia

Location

City Hospital #4

Sochi, 354057, Russia

Location

Clinic for Infectious Diseases, Clinical Center Nis

Niš, Serbia

Location

Korea University Anam Hospital

Seongdu, South Korea

Location

Asan Medical Center

Seoul, South Korea

Location

Samsung Medical Center [Pulmonology]

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

Complexo Hospitalario Universitario A Coruña

A Coruña, Spain

Location

Hospital Universitario Mutua Terrassa Intensive Care

Barcelona, Spain

Location

Servicio de Medicina Intensiva Hospital Universitario Valle de Hebron

Barcelona, Spain

Location

Hospital Clínico San Carlos

Madrid, Spain

Location

Hospital de Sabadell

Sabadell, Spain

Location

Hospital Universitari de Tarragona Joan XXIII

Tarragona, Spain

Location

Chi Mei Medical Center Yong Kang

Yongkang District, Tainan, Taiwan

Location

Taichung Veterans General Hospital [Pulmonology]

Taichung, Taiwan

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

Birmingham Heartlands Hospital

Birmingham, B9 5SS, United Kingdom

Location

Hull Royal Infirmary

Hull, HU3 2JZ, United Kingdom

Location

Royal Liverpool University Hospital

Liverpool, United Kingdom

Location

Manchester Royal Infirmary

Manchester, United Kingdom

Location

Derriford Hospital

Plymouth, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 32697484 DERIVED

• 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.

  PMID: 31104069 DERIVED

Related Links

• Information on sepsis and treatment

MeSH Terms

Conditions

Sepsis; Hemostatic Disorders

Interventions

ART123

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Director of Clinical Operations
• Organization: Asahi Kasei Pharma America Corp.

pallton@akpamerica.com

(781) 419-1919

Study Officials

• David Fineberg, M.D.

  Asahi Kasei Pharma America Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2012
• First Posted: May 15, 2012
• Study Start: October 29, 2012
• Primary Completion: April 5, 2018
• Study Completion: February 28, 2019
• Last Updated: April 21, 2020
• Results First Posted: April 21, 2020

Record last verified: 2020-03

Locations

AU (10); BE (11); NL (8); AR (1); DE (3); RU (12); GB (5); BR (3); CZ (5); PE (2); FR (16); TW (3); CA (14); ES (6); NZ (4); IL (6); KR (4); SE (1); CR (3); US (22); HU (1); BU (2); FI (4); IN (15)