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

Severe Sepsis Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01598831
• Other study ID #: 3-001
• Status: Completed
• Phase: Phase 3
• Start date: October 29, 2012
• Est. completion date: February 28, 2019

Study information

• Verified date: March 2020
• Source: Asahi Kasei Pharma America Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 816
• Est. completion date: February 28, 2019
• Est. primary completion date: April 5, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Blood Coagulation Disorders
• Coagulopathy
• Hemostatic Disorders
• Sepsis
• Severe Sepsis
• Toxemia

Intervention

Drug:
• ART-123
Dose: 0.06 mg/kg/day up to a maximum dose of 6 mg/day for 6 days
• Placebo
Dose: 0.06 mg/kg/day up to a maximum dose of 6 mg/day for 6 days.

Locations

Country	Name	City	State
Argentina	Hospital Italiano de Cordoba	Cordoba
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	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	Sunshine Hospital	Melbourne	Victoria
Australia	Prince of Wales Hospital	Randwick	New South Wales
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
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
Brazil	Santa Casa de Misericordia de Belo Horizonte	Belo Horizonte	MG
Brazil	Hospital Pompéia	Brasil
Brazil	Fundaçao Faculdade Regional de Medicina Sao Jose do Rio Preto	Sao Jose do Rio Preto	SP
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
Canada	2 of 2	Calgary	Alberta
Canada	1 of 2	Ottawa	Ontario
Canada	2 of 2	Ottawa	Ontario
Canada	2 of 2	Vancouver	British Columbia
Canada	1 of 2	Victoria	British Columbia
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
Czechia	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
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
France	CHU D'Anger	Angers Cedex 9
France	CHU de Dijon, Hopital Bocage Central	Dijon
France	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	CHU Limoges	Limoges cedex
France	Service de reanimation médicale. CHU Hotel Dieu	Nantes	Nantes Cedex 01
France	Archet 1 University Hospital of Nice	Nice	Cedex 3
France	Centre Hospitalier Universitaire Nîmes	Nîmes Cedex 9
France	Hôpital COCHIN	Paris
France	La Pitié Salpétrière, Paris	Paris
France	University Hospital of Bordeaux	Pessac
France	CH Lyon Sud	Pierre-Bénite cedex
France	Nouvel hospital civil	Strasbourg
France	Hôpital Sainte Musse	Toulon
France	CHU Tours, Hopital Bretonneau	Tours
Germany	Universitätsklinikum der RWTH Aachen	Aachen
Germany	Helios Klinikum Erfurt	Erfurt
Germany	Klinikum der Johann-Wolfgang Goethe-Universität	Frankfurt am Main
Hungary	Szent Imre Hospital, Anesthesiology and Intensive Care Unit	Budapest
India	Shalby	Ahmedabad	Gujarat
India	Shalby Hospital	Ahmedabad,	Gujarat
India	Mazumdar Shaw Medical Centre (Unit of Narayana Health)	Bangalore
India	KLES Dr. Prabhakar Kore Hospital & Medical Research Centre	Belgaum
India	Hi-tech Medical College & Hospital	Bhubaneswar	Odisha
India	Artemis Hospital	Gurgaon	Haryana
India	St. Theresa Hospital	Hyderabad	Telangana State
India	JSS Hospital	Mysore
India	Care Hospital	Nagpur
India	Maulana Azad Medical College and Associated L N Hospital	New Delhi	Delhi
India	Bharati Vidyapeeth Deemed University Medical College Bharti Hospital and Research Centre	Pune	Pune, Maharashtra
India	King Edward Memorial Hospital & Research Centre	Pune	Maharashtra
India	Noble Hospital	Pune	Maharashtra
India	Noble Hospital	Pune
India	Ruby Hall Clinic	Pune	Maharashtra
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
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
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	Medisch Centrum Leeuwarden	Leeuwarden
Netherlands	UMC St. Radboud	Nijmegen
Netherlands	Ikazia Ziekenhuis	Rotterdam
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
Peru	Hospital Nacional Almenara Yrigoyen - EsSALUD	Lima	Lima Province
Peru	Hospital Nacional FAP	Lima	Lima Province
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	Kuban State Medical University (Site Facility: Krasnodar Regional Clinical Hospital #2)	Krasnodar
Russian Federation	Krasnoyarsk Regional Clinocal Hospital	Krasnoyarsk
Russian Federation	Vishnevsky Institute of Surgery	Moscow
Russian Federation	City Hospital #40	Saint Petersburg
Russian Federation	St George City Hospital	Saint Petersburg
Russian Federation	City Hospital #4	Sochi
Russian Federation	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
Serbia	Clinic for Infectious Diseases, Clinical Center Nis	Nis
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
Taiwan	Taichung Veterans General Hospital [Pulmonology]	Taichung
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Chi Mei Medical Center Yong Kang	Yongkang	Tainan
United Kingdom	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 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	2 of 2	Houston	Texas
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Washington University in St. Louis	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Asahi Kasei Pharma America Corporation

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Bulgaria,  Canada,  Croatia,  Czechia,  Finland,  France,  Germany,  Hungary,  India,  Israel,  Korea, Republic of,  Netherlands,  New Zealand,  Peru,  Russian Federation,  Serbia,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With 28-Day All-cause Mortality	28-Day All-cause Mortality	28 days
Primary	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	Follow up All-cause Mortality at 3 Months	Follow up all-cause mortality at 3 months	3 months
Secondary	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.	28 days
Secondary	Number of Participants With Anti-drug Antibodies	Presence of Anti-drug antibodies up to 18 months	18 months

External Links

•   Information on sepsis and treatment