Clinical trial NCT01598831: Phase 3 Safety and Efficacy Study of ART-123 in Subjects With Severe Sepsis and Coagulopathy
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Severe Sepsis
Coagulopathy
Keywords: sepsis
Lead sponsor: Asahi Kasei Pharma America Corporation
Sponsor class: INDUSTRY
First posted: 2012-05-15
Enrollment: 816
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Participants With 28-Day All-cause Mortality
timeFrame: 28 days
measure: Number of Participants With On-Treatment Serious Major Bleeding Events
timeFrame: Through Study Day 28
Secondary outcomes:
measure: Follow up All-cause Mortality at 3 Months
timeFrame: 3 months
measure: Number of Event Free and Alive Days to Measure Resolution of Organ Dysfunction
timeFrame: 28 days
measure: Number of Participants With Anti-drug Antibodies
timeFrame: 18 months
Other outcomes:
Locations:
city: Mobile
country: United States
state: Alabama
city: Phoenix
country: United States
state: Arizona
city: Atlanta
country: United States
state: Georgia
city: Idaho Falls
country: United States
state: Idaho
city: Indianapolis
country: United States
state: Indiana
city: Hazard
country: United States
state: Kentucky
city: Louisville
country: United States
state: Kentucky
city: Detroit
country: United States
facility: Detroit Receiving Hospital
state: Michigan
city: Detroit
country: United States
facility: Harper Hospital - Wayne State University School of Medicine
state: Michigan
city: Detroit
country: United States
facility: Sinai-Grace Hospital
state: Michigan
city: Jackson
country: United States
state: Mississippi
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: Butte
country: United States
state: Montana
city: Englewood
country: United States
state: New Jersey
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
state: North Carolina
city: Columbus
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Philadelphia
country: United States
state: Pennsylvania
city: Rapid City
country: United States
state: South Dakota
city: Houston
country: United States
facility: 2 of 2
state: Texas
city: Murray
country: United States
state: Utah
city: Cordoba
country: Argentina
facility: Hospital Italiano de Cordoba
city: Randwick
country: Australia
facility: Prince of Wales Hospital
state: New South Wales
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Bendigo
country: Australia
facility: Bendigo Hospital
state: Victoria
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Dandenong
country: Australia
facility: Dandenong Hospital Monash Health
state: Victoria
city: Footscray
country: Australia
facility: Western Hospital
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Melbourne
country: Australia
facility: Sunshine Hospital
state: Victoria
city: Antwerpen
country: Belgium
facility: UZ Antwerpen
city: Arlon
country: Belgium
facility: Cliniques Du Sud-Luxerbourg (CSL), Hospital Saint Joseph
city: Brussels
country: Belgium
facility: CHU Brugmann
city: Brussels
country: Belgium
facility: Hopital Erasme
city: Brussels
country: Belgium
facility: Hopitaux Iris Sud
city: Brussels
country: Belgium
facility: UCL St. Luc
city: Brussels
country: Belgium
facility: UZ Brussel
city: Dinant
country: Belgium
facility: Centre Hospitalier de Dinant
city: Gent
country: Belgium
facility: UZ Gent
city: Ottignies
country: Belgium
facility: Clinique Saint-Pierre
city: Yvoir
country: Belgium
facility: UCL Mont-Godinne
city: Belo Horizonte
country: Brazil
facility: Santa Casa de Misericordia de Belo Horizonte
state: MG
city: Sao Jose do Rio Preto
country: Brazil
facility: Fundaçao Faculdade Regional de Medicina Sao Jose do Rio Preto
state: SP
city: Brasil
country: Brazil
facility: Hospital Pompéia
city: Plovdiv
country: Bulgaria
facility: Anesthesiology and Intensive Care Clinic, University Multiprofile Hospital For Active Treatment "Sveti Georgi", Plovdiv
city: Sofia
country: Bulgaria
facility: Department of Anesthesiology and Intensive Care Multiprofile Hospital For Active Treatment "Tokuda Hospital Sofia", Sofia
city: Calgary
country: Canada
facility: 2 of 2
state: Alberta
city: Calgary
country: Canada
state: Alberta
city: Calgary
country: Canada
state: Alberta
city: Vancouver
country: Canada
state: British Columbia
city: Vancouver
country: Canada
facility: 2 of 2
state: British Columbia
city: Victoria
country: Canada
facility: 1 of 2
state: British Columbia
city: Victoria
country: Canada
state: British Columbia
city: Winnipeg
country: Canada
state: Manitoba
city: Halifax
country: Canada
state: Nova Scotia
city: London
country: Canada
state: Ontario
city: Ottawa
country: Canada
facility: 1 of 2
state: Ontario
city: Ottawa
country: Canada
facility: 2 of 2
state: Ontario
city: Windsor
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Zagreb
country: Croatia
facility: Clinical Hospital Center Zagreb, Medical ICU
city: Zagreb
country: Croatia
facility: Clinical Hospital Dubrava, Department of Anesthesiology and resuscitation
city: Zagreb
country: Croatia
facility: University Hospital Center Zagreb, Department of Anesthesiology, Reanimatology and Intensive Care Medicine
city: Brno
country: Czechia
facility: University Hospital Brno, Department of Infectious Diseases
city: Hradec Kralove
country: Czechia
facility: University Hospital Hradec Kralove, Department of Anaesthesiology, Resuscitation and Intensive Care
city: Prague 10
country: Czechia
facility: University Hospital Kralovske Vinohrady, Department of Anesthesiology and Resuscitation
city: Prague 2
country: Czechia
facility: General University Hospital in Prague, Department of Anaesthesiology, Resuscitation and Intensive Medicine
city: Usti nad Labem
country: Czechia
facility: Masaryk´s Hospital Ustni nad Labem, o.z., Department of Infectious Diseases
city: Helsinki
country: Finland
facility: Helsingin Yliopistollinen Keskussairaala (HYKS) (Helsinki University Central Hospital (HUCH))
city: Jyväskylä
country: Finland
facility: Keski-Suomen Keskussairaala (Central Finland Central Hospital)
city: Kuopio
country: Finland
facility: Kuopion Yliopistollinen Sairaala (KYS) (Kuopio University Hospital)
city: Tampere
country: Finland
facility: Tampereen Yliopistollinen Sairaala (Tampere University Hospital) (TAYS) - Keskussairaala (Central Hospital)
city: Nice
country: France
facility: Archet 1 University Hospital of Nice
state: Cedex 3
city: Nantes
country: France
facility: Service de reanimation médicale. CHU Hotel Dieu
state: Nantes Cedex 01
city: Angers Cedex 9
country: France
facility: CHU D'Anger
city: Dijon
country: France
facility: CHU de Dijon, Hopital Bocage Central
city: Grenoble cedex 09
country: France
facility: CH-Hôpital Albert Michallon
city: La Roche-Sur-Yon cedex 9
country: France
facility: Centre Hospitalier Départemental de Vendée-Les Oudairies
city: Lille
country: France
facility: CHRU Lille-Pole Reanimation
city: Limoges cedex
country: France
facility: CHU Limoges
city: Nîmes Cedex 9
country: France
facility: Centre Hospitalier Universitaire Nîmes
city: Paris
country: France
facility: La Pitié Salpétrière, Paris
city: Paris
country: France
facility: Hôpital COCHIN
city: Pessac
country: France
facility: University Hospital of Bordeaux
city: Pierre-Bénite cedex
country: France
facility: CH Lyon Sud
city: Strasbourg
country: France
facility: Nouvel hospital civil
city: Toulon
country: France
facility: Hôpital Sainte Musse
city: Tours
country: France
facility: CHU Tours, Hopital Bretonneau
city: Aachen
country: Germany
facility: Universitätsklinikum der RWTH Aachen
city: Erfurt
country: Germany
facility: Helios Klinikum Erfurt
city: Frankfurt am Main
country: Germany
facility: Klinikum der Johann-Wolfgang Goethe-Universität
city: Budapest
country: Hungary
facility: Szent Imre Hospital, Anesthesiology and Intensive Care Unit
city: New Delhi
country: India
facility: Maulana Azad Medical College and Associated L N Hospital
state: Delhi
city: Ahmedabad,
country: India
facility: Shalby Hospital
state: Gujarat
city: Ahmedabad
country: India
facility: Shalby
state: Gujarat
city: Gurgaon
country: India
facility: Artemis Hospital
state: Haryana
city: Pune
country: India
facility: Ruby Hall Clinic
state: Maharashtra
city: Pune
country: India
facility: Noble Hospital
state: Maharashtra
city: Pune
country: India
facility: King Edward Memorial Hospital & Research Centre
state: Maharashtra
city: Bhubaneswar
country: India
facility: Hi-tech Medical College & Hospital
state: Odisha
city: Pune
country: India
facility: Bharati Vidyapeeth Deemed University Medical College Bharti Hospital and Research Centre
state: Pune, Maharashtra
city: Hyderabad
country: India
facility: St. Theresa Hospital
state: Telangana State
city: Bangalore
country: India
facility: Mazumdar Shaw Medical Centre (Unit of Narayana Health)
city: Belgaum
country: India
facility: KLES Dr. Prabhakar Kore Hospital & Medical Research Centre
city: Mysore
country: India
facility: JSS Hospital
city: Nagpur
country: India
facility: Care Hospital
city: Pune
country: India
facility: Noble Hospital
city: Ashkelon
country: Israel
facility: Barzilai Medical Center
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Haifa
country: Israel
facility: The Lady Davis Carmel Medical Center
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Petach Tikva
country: Israel
facility: Rabin Medical Center
city: Rehovot
country: Israel
facility: Kaplan Medical Center
city: Seongdu
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center [Pulmonology]
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: 's-Hertogenbosch
country: Netherlands
facility: Jeroen Bosch Ziekenhuis
city: Amsterdam
country: Netherlands
facility: VUMC
city: Ede
country: Netherlands
facility: Ziekenhuis Gelderse Vallei
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Leeuwarden
country: Netherlands
facility: Medisch Centrum Leeuwarden
city: Nijmegen
country: Netherlands
facility: UMC St. Radboud
city: Rotterdam
country: Netherlands
facility: Ikazia Ziekenhuis
city: Auckland
country: New Zealand
facility: Auckland District Health Board
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Hastings
country: New Zealand
facility: Hawkes Bay Regional Hospital Intensive Care Unit Omahu Road
city: Newtown
country: New Zealand
facility: Wellington District Health Board
city: Lima
country: Peru
facility: Hospital Nacional Almenara Yrigoyen - EsSALUD
state: Lima Province
city: Lima
country: Peru
facility: Hospital Nacional FAP
state: Lima Province
city: Arkhangelsk
country: Russian Federation
facility: Arkhangelsk Regional Clinical Hospital
city: Arkhangelsk
country: Russian Federation
facility: Volosevich City Clinical Hospital #1
city: Kemerovo
country: Russian Federation
facility: City Clinical Hospital #3 n.a. M.A. Pogorbunskiy
city: Krasnodar
country: Russian Federation
facility: Kuban State Medical University (Site Facility: Krasnodar Regional Clinical Hospital #2)
city: Krasnoyarsk
country: Russian Federation
facility: Krasnoyarsk Regional Clinocal Hospital
city: Moscow
country: Russian Federation
facility: Vishnevsky Institute of Surgery
city: Saint Petersburg
country: Russian Federation
facility: St George City Hospital
city: Saint Petersburg
country: Russian Federation
facility: City Hospital #40
city: Sochi
country: Russian Federation
facility: City Hospital #4
city: St. Petersburg
country: Russian Federation
facility: Aleksandrovskaya City Hospital
city: St. Petersburg
country: Russian Federation
facility: Mariinskaya City Hospital
city: St. Petersburg
country: Russian Federation
facility: Mechnikov North-Western State Medical University n.a. I.I. Mechnikov
city: Nis
country: Serbia
facility: Clinic for Infectious Diseases, Clinical Center Nis
city: A Coruña
country: Spain
facility: Complexo Hospitalario Universitario A Coruña
city: Barcelona
country: Spain
facility: Hospital Universitario Mutua Terrassa Intensive Care
city: Barcelona
country: Spain
facility: Servicio de Medicina Intensiva Hospital Universitario Valle de Hebron
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Sabadell
country: Spain
facility: Hospital de Sabadell
city: Tarragona
country: Spain
facility: Hospital Universitari de Tarragona Joan XXIII
city: Yongkang
country: Taiwan
facility: Chi Mei Medical Center Yong Kang
state: Tainan
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital [Pulmonology]
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
city: Hull
country: United Kingdom
facility: Hull Royal Infirmary
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital
city: Manchester
country: United Kingdom
facility: Manchester Royal Infirmary
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
Study officials:
affiliation: Asahi Kasei Pharma America Corporation
name: David Fineberg, M.D.
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.