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Severe SepsisPhase 3NCT01598831

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

A Phase 3 study testing ART-123 in people with Severe Sepsis and Coagulopathy, run by Asahi Kasei Pharma America Corporation at 161 sites in 24 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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

Who is it for?
Ages 18 years and older
Conditions the study is for
Severe Sepsis, Coagulopathy
What is being tested?
ART-123
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
816 participants
Where
161 sitesin 24 countries
Study dates
29 Oct 2012to 28 Feb 2019
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 27Show fewer
  • 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

Trial locations and contacts

161 sites in 24 countries.

161 sites in 24 countries

United States22 sites

  • Study site

    Atlanta, Georgia, 30342

  • Study site

    Butte, Montana, 59701

  • Study site

    Columbus, Ohio, 43215

  • Detroit Receiving Hospital

    Detroit, Michigan, 48201

  • Harper Hospital - Wayne State University School of Medicine

    Detroit, Michigan, 48201

  • Sinai-Grace Hospital

    Detroit, Michigan, 48235

  • Study site

    Durham, North Carolina, 27710

  • Study site

    Englewood, New Jersey, 07631

  • Study site

    Hazard, Kentucky, 41701

  • 2 of 2

    Houston, Texas, 77030

  • Study site

    Idaho Falls, Idaho, 83404

  • Study site

    Indianapolis, Indiana, 46202

  • Study site

    Jackson, Mississippi, 39216

  • Study site

    Louisville, Kentucky, 40202

  • Study site

    Mobile, Alabama, 36608

  • Study site

    Murray, Utah, 84107

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Study site

    Oklahoma City, Oklahoma, 73104

  • Study site

    Philadelphia, Pennsylvania, 19104

  • Study site

    Phoenix, Arizona, 85008

  • Study site

    Rapid City, South Dakota, 57701

  • Washington University in St. Louis

    St Louis, Missouri, 63110

Other trials in United States

France16 sites

  • CHU D'Anger

    Angers

  • CHU de Dijon, Hopital Bocage Central

    Dijon, 21000

  • CH-Hôpital Albert Michallon

    Grenoble

  • Centre Hospitalier Départemental de Vendée-Les Oudairies

    La Roche-sur-Yon

  • CHRU Lille-Pole Reanimation

    Lille, 59037

  • CHU Limoges

    Limoges

  • Service de reanimation médicale. CHU Hotel Dieu

    Nantes, Nantes Cedex 01, 44093

  • Archet 1 University Hospital of Nice

    Nice, Cedex 3, 23079

  • Centre Hospitalier Universitaire Nîmes

    Nîmes

  • La Pitié Salpétrière, Paris

    Paris, 75013

  • Hôpital COCHIN

    Paris

  • University Hospital of Bordeaux

    Pessac, 33600

  • CH Lyon Sud

    Pierre-Bénite

  • Nouvel hospital civil

    Strasbourg, 67000

  • Hôpital Sainte Musse

    Toulon

  • CHU Tours, Hopital Bretonneau

    Tours

Other trials in France

India15 sites

  • Shalby Hospital

    Ahmedabad, Gujarat, 380015

  • Shalby

    Ahmedabad, Gujarat

  • Mazumdar Shaw Medical Centre (Unit of Narayana Health)

    Bangalore, 560099

  • KLES Dr. Prabhakar Kore Hospital & Medical Research Centre

    Belagavi, 590010

  • Hi-tech Medical College & Hospital

    Bhubaneswar, Odisha

  • Artemis Hospital

    Gurgaon, Haryana, 122001

  • St. Theresa Hospital

    Hyderabad, Telangana State, 500018

  • JSS Hospital

    Mysore, 570004

  • Care Hospital

    Nagpur, 440010

  • Maulana Azad Medical College and Associated L N Hospital

    New Delhi, National Capital Territory of Delhi

  • Ruby Hall Clinic

    Pune, Maharashtra, 411011

  • Noble Hospital

    Pune, Maharashtra, 411013

  • King Edward Memorial Hospital & Research Centre

    Pune, Maharashtra

  • Bharati Vidyapeeth Deemed University Medical College Bharti Hospital and Research Centre

    Pune, Pune, Maharashtra, 411043

  • Noble Hospital

    Pune, 411013

Other trials in India

Canada14 sites

  • 2 of 2

    Calgary, Alberta, T1Y 6J4

  • Study site

    Calgary, Alberta, T2V 1PA

  • Study site

    Calgary, Alberta, T3M 1M4

  • Study site

    Halifax, Nova Scotia

  • Study site

    London, Ontario, N6A5W9

  • Study site

    Montreal, Quebec

  • 1 of 2

    Ottawa, Ontario, KIH 8L6

  • 2 of 2

    Ottawa, Ontario, KIH 8L6

  • Study site

    Vancouver, British Columbia, V5Z 1M9

  • 2 of 2

    Vancouver, British Columbia, V6Z 1Y6

  • 1 of 2

    Victoria, British Columbia, V8R-1J8

  • Study site

    Victoria, British Columbia, V8R1J8

  • Study site

    Windsor, Ontario

  • Study site

    Winnipeg, Manitoba

Other trials in Canada

Russia12 sites

  • Arkhangelsk Regional Clinical Hospital

    Arkhangelsk

  • Volosevich City Clinical Hospital #1

    Arkhangelsk

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

    Kemerovo, 650000

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

    Krasnodar

  • Krasnoyarsk Regional Clinocal Hospital

    Krasnoyarsk, 660022

  • Vishnevsky Institute of Surgery

    Moscow

  • St George City Hospital

    Saint Petersburg, 194354

  • Aleksandrovskaya City Hospital

    Saint Petersburg

  • City Hospital #40

    Saint Petersburg

  • Mariinskaya City Hospital

    Saint Petersburg

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

    Saint Petersburg

  • City Hospital #4

    Sochi, 354057

Other trials in Russia

Belgium11 sites

  • UZ Antwerpen

    Antwerp

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

    Arlon

  • CHU Brugmann

    Brussels

  • Hopital Erasme

    Brussels

  • Hopitaux Iris Sud

    Brussels

  • UCL St. Luc

    Brussels

  • UZ Brussel

    Brussels

  • Centre Hospitalier de Dinant

    Dinant

  • UZ Gent

    Ghent

  • Clinique Saint-Pierre

    Ottignies

  • UCL Mont-Godinne

    Yvoir

Other trials in Belgium

Australia10 sites

  • Royal Adelaide Hospital

    Adelaide, South Australia, 5000

  • Bendigo Hospital

    Bendigo, Victoria

  • Monash Medical Centre

    Clayton, Victoria

  • Dandenong Hospital Monash Health

    Dandenong, Victoria, 3175

  • Western Hospital

    Footscray, Victoria

  • Austin Health

    Heidelberg, Victoria

  • Royal Brisbane and Women's Hospital

    Herston, Queensland

  • Sunshine Hospital

    Melbourne, Victoria, 3021

  • Prince of Wales Hospital

    Randwick, New South Wales

  • Princess Alexandra Hospital

    Woolloongabba, Queensland

Other trials in Australia

Netherlands8 sites

  • Jeroen Bosch Ziekenhuis

    's-Hertogenbosch

  • VUMC

    Amsterdam

  • Ziekenhuis Gelderse Vallei

    Ede

  • Medisch Spectrum Twente

    Enschede

  • University Medical Center Groningen

    Groningen

  • Medisch Centrum Leeuwarden

    Leeuwarden

  • UMC St. Radboud

    Nijmegen

  • Ikazia Ziekenhuis

    Rotterdam

Other trials in Netherlands

Israel6 sites

  • Barzilai Medical Center

    Ashkelon

  • Rambam Medical Center

    Haifa

  • The Lady Davis Carmel Medical Center

    Haifa

  • Shaare Zedek Medical Center

    Jerusalem

  • Rabin Medical Center

    Petah Tikva

  • Kaplan Medical Center

    Rehovot

Other trials in Israel

Spain6 sites

  • Complexo Hospitalario Universitario A Coruña

    A Coruña

  • Hospital Universitario Mutua Terrassa Intensive Care

    Barcelona

  • Servicio de Medicina Intensiva Hospital Universitario Valle de Hebron

    Barcelona

  • Hospital Clínico San Carlos

    Madrid

  • Hospital de Sabadell

    Sabadell

  • Hospital Universitari de Tarragona Joan XXIII

    Tarragona

Other trials in Spain

Czechia5 sites

  • University Hospital Brno, Department of Infectious Diseases

    Brno

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

    Hradec Králové

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

    Prague

  • University Hospital Kralovske Vinohrady, Department of Anesthesiology and Resuscitation

    Prague

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

    Ústí nad Labem

Other trials in Czechia

United Kingdom5 sites

  • Birmingham Heartlands Hospital

    Birmingham, B9 5SS

  • Hull Royal Infirmary

    Hull, HU3 2JZ

  • Royal Liverpool University Hospital

    Liverpool

  • Manchester Royal Infirmary

    Manchester

  • Derriford Hospital

    Plymouth

Other trials in United Kingdom

Finland4 sites

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

    Helsinki

  • Keski-Suomen Keskussairaala (Central Finland Central Hospital)

    Jyväskylä

  • Kuopion Yliopistollinen Sairaala (KYS) (Kuopio University Hospital)

    Kuopio

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

    Tampere

Other trials in Finland

New Zealand4 sites

  • Auckland District Health Board

    Auckland

  • Christchurch Hospital

    Christchurch

  • Hawkes Bay Regional Hospital Intensive Care Unit Omahu Road

    Hastings

  • Wellington District Health Board

    Newtown, 6021

Other trials in New Zealand

South Korea4 sites

  • Korea University Anam Hospital

    Seongdu

  • Asan Medical Center

    Seoul

  • Samsung Medical Center [Pulmonology]

    Seoul

  • Seoul National University Hospital

    Seoul

Other trials in South Korea

Brazil3 sites

  • Santa Casa de Misericordia de Belo Horizonte

    Belo Horizonte, Minas Gerais

  • Hospital Pompéia

    Brasil, 95010-005

  • Fundaçao Faculdade Regional de Medicina Sao Jose do Rio Preto

    São José do Rio Preto, São Paulo

Other trials in Brazil

Croatia3 sites

  • Clinical Hospital Center Zagreb, Medical ICU

    Zagreb

  • Clinical Hospital Dubrava, Department of Anesthesiology and resuscitation

    Zagreb

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

    Zagreb

Other trials in Croatia

Germany3 sites

  • Universitätsklinikum der RWTH Aachen

    Aachen, 54074

  • Helios Klinikum Erfurt

    Erfurt

  • Klinikum der Johann-Wolfgang Goethe-Universität

    Frankfurt am Main

Other trials in Germany

Taiwan3 sites

  • Taichung Veterans General Hospital [Pulmonology]

    Taichung

  • National Taiwan University Hospital

    Taipei

  • Chi Mei Medical Center Yong Kang

    Yongkang District, Tainan

Other trials in Taiwan

Bulgaria2 sites

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

    Plovdiv

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

    Sofia

Other trials in Bulgaria

Peru2 sites

  • Hospital Nacional Almenara Yrigoyen - EsSALUD

    Lima, Lima Province

  • Hospital Nacional FAP

    Lima, Lima Province

Other trials in Peru

Argentina1 site

  • Hospital Italiano de Cordoba

    Córdoba, X5004BAL

Other trials in Argentina

Hungary1 site

  • Szent Imre Hospital, Anesthesiology and Intensive Care Unit

    Budapest, 1115

Other trials in Hungary

Serbia1 site

  • Clinic for Infectious Diseases, Clinical Center Nis

    Niš

Other trials in Serbia

About this study

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.

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

Read the 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.

Being tested
ART-123, Placebo
Keywords
sepsis
Medical subject headings
Sepsis, Hemostatic Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ART-123Drug

    Also called human recombinant thrombomodulin, thrombomodulin alfa

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

  • PlaceboDrug

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

Study groups in NCT01598831
Study groupRoleWhat they receive
ART-123Active comparatorNot described
Receives: Drug: ART-123
PlaceboPlacebo comparatorNot described
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With 28-Day All-cause Mortality

    28-Day All-cause Mortality

    Measured: 28 days

  2. 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.)

    Measured: Through Study Day 28

Secondary outcomes (3)

  1. Follow up All-cause Mortality at 3 Months

    Follow up all-cause mortality at 3 months

    Measured: 3 months

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

    Resolution of organ dysfunction as measured through day 28 by shock free, ventilator free, dialysis free plus alive days.

    Measured: 28 days

  3. Number of Participants With Anti-drug Antibodies

    Presence of Anti-drug antibodies up to 18 months

    Measured: 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 May 2012 (estimated)
  2. Study start29 Oct 2012
  3. Primary completion5 Apr 2018
  4. Study completion28 Feb 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
816 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01598831
Sponsor's protocol ID
3-001
Status last verified
Mar 2020
First submitted
11 May 2012
Last updated
21 Apr 2020
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 32697484

  • 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.

    PubMed 31104069

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing ART-123 in people with Severe Sepsis and Coagulopathy, run by Asahi Kasei Pharma America Corporation at 161 sites in 24 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 161 sites in United States, France, India, Canada, Russia and 19 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Apr 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With 28-Day All-cause Mortality (time frame: 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01598831, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Apr 2020.

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